TBD Meeting (5304-21)

It’s time for a large-scale phase 2 study into whether supplementary estrogen can relieve multiple sclerosis (MS) symptoms in menopausal women with the disease, a neurologist told colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

This kind of research should explore the effects of aging, including in the brain, and “focus on what is preventable – this dramatic and abrupt loss of estrogen in women with MS,” said Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles.

“This is a call to action. There’s a huge gap that needs to be filled,” she added in an interview. “Not enough attention has been paid to menopause and cognitive issues in MS and even in healthy women.”

Research has found that many women with MS experience a decline in function during menopause, she said. “They’re having a worsening of their preexisting disabilities,” she noted, due to neurodegeneration.

Dr. Voskuhl highlighted a 2016 study, for instance, that found postmenopausal women with MS on hormone replacement therapy reported better physical function and quality of life than did their counterparts after adjustment for covariates. She also pointed to a 2019 study that concluded that “natural menopause seems to be a turning point to a more progressive phase of MS.”

Estrogen appears to play a significant role. “It’s involved in synaptic plasticity,” she said. “That’s why the disabilities are worsening.”

Dr. Voskuhl supports a year-long, randomized and controlled study of estrogen supplementation in 150-200 participants. The goal, she said, is “not just to prevent loss and bad things from happening but also make improvements.”

In healthy patients, she said, outcomes should include cognitive decline in menopause, cognitive domain outcomes, and region-specific biomarkers in the frontal cortex and hippocampus instead of global cognition and global brain volume. In patients with MS, she said, the focus should be on worsening of disability with emphasis on specific disabilities such as walking and region-specific biomarkers for the motor cortex and spinal cord.

“We need to be looking at cortical gray matter, which we know is responsive to estrogen,” Dr. Voskuhl said. She led a 2018 placebo-controlled study that found women with MS who took estrogen supplements appeared to experience localized sparing of progressive gray matter, which the researchers linked to improved results in cognitive testing. The findings, the study authors wrote, suggest “a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.”

What about men? Does hormone loss worsen their MS? Dr. Voskuhl said there seems to be a connection between lower levels of testosterone and more disability in men with MS. But their situation is different. Loss of testosterone in men is gradual and happens over decades instead of over the short period of menopause in women, she said.

Jennifer Graves, MD, a neurologist at the University of California, San Diego, agreed that it’s time for further research into estrogen supplementation in MS. As she noted, “we don’t know the exact biological mechanism that might link perimenopause with developing a more progressive type of MS.”

She added: “An overall decrease in estrogen may be at play but there are other biological changes around menopause. We must also take care in studies to try to separate out what might be due to ovarian aging versus other types of aging processes that might be happening at the same time.”

Dr. Voskuhl disclosed that she is an inventor on university patents for use of estriol and estrogen receptor–beta ligands as treatments. Dr. Graves reports no relevant disclosures.

It’s time for a large-scale phase 2 study into whether supplementary estrogen can relieve multiple sclerosis (MS) symptoms in menopausal women with the disease, a neurologist told colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

This kind of research should explore the effects of aging, including in the brain, and “focus on what is preventable – this dramatic and abrupt loss of estrogen in women with MS,” said Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles.

“This is a call to action. There’s a huge gap that needs to be filled,” she added in an interview. “Not enough attention has been paid to menopause and cognitive issues in MS and even in healthy women.”

Research has found that many women with MS experience a decline in function during menopause, she said. “They’re having a worsening of their preexisting disabilities,” she noted, due to neurodegeneration.

Dr. Voskuhl highlighted a 2016 study, for instance, that found postmenopausal women with MS on hormone replacement therapy reported better physical function and quality of life than did their counterparts after adjustment for covariates. She also pointed to a 2019 study that concluded that “natural menopause seems to be a turning point to a more progressive phase of MS.”

Estrogen appears to play a significant role. “It’s involved in synaptic plasticity,” she said. “That’s why the disabilities are worsening.”

Dr. Voskuhl supports a year-long, randomized and controlled study of estrogen supplementation in 150-200 participants. The goal, she said, is “not just to prevent loss and bad things from happening but also make improvements.”

In healthy patients, she said, outcomes should include cognitive decline in menopause, cognitive domain outcomes, and region-specific biomarkers in the frontal cortex and hippocampus instead of global cognition and global brain volume. In patients with MS, she said, the focus should be on worsening of disability with emphasis on specific disabilities such as walking and region-specific biomarkers for the motor cortex and spinal cord.

“We need to be looking at cortical gray matter, which we know is responsive to estrogen,” Dr. Voskuhl said. She led a 2018 placebo-controlled study that found women with MS who took estrogen supplements appeared to experience localized sparing of progressive gray matter, which the researchers linked to improved results in cognitive testing. The findings, the study authors wrote, suggest “a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.”

What about men? Does hormone loss worsen their MS? Dr. Voskuhl said there seems to be a connection between lower levels of testosterone and more disability in men with MS. But their situation is different. Loss of testosterone in men is gradual and happens over decades instead of over the short period of menopause in women, she said.

Jennifer Graves, MD, a neurologist at the University of California, San Diego, agreed that it’s time for further research into estrogen supplementation in MS. As she noted, “we don’t know the exact biological mechanism that might link perimenopause with developing a more progressive type of MS.”

She added: “An overall decrease in estrogen may be at play but there are other biological changes around menopause. We must also take care in studies to try to separate out what might be due to ovarian aging versus other types of aging processes that might be happening at the same time.”

Dr. Voskuhl disclosed that she is an inventor on university patents for use of estriol and estrogen receptor–beta ligands as treatments. Dr. Graves reports no relevant disclosures.

It’s time for a large-scale phase 2 study into whether supplementary estrogen can relieve multiple sclerosis (MS) symptoms in menopausal women with the disease, a neurologist told colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

This kind of research should explore the effects of aging, including in the brain, and “focus on what is preventable – this dramatic and abrupt loss of estrogen in women with MS,” said Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles.

“This is a call to action. There’s a huge gap that needs to be filled,” she added in an interview. “Not enough attention has been paid to menopause and cognitive issues in MS and even in healthy women.”

Research has found that many women with MS experience a decline in function during menopause, she said. “They’re having a worsening of their preexisting disabilities,” she noted, due to neurodegeneration.

Dr. Voskuhl highlighted a 2016 study, for instance, that found postmenopausal women with MS on hormone replacement therapy reported better physical function and quality of life than did their counterparts after adjustment for covariates. She also pointed to a 2019 study that concluded that “natural menopause seems to be a turning point to a more progressive phase of MS.”

Estrogen appears to play a significant role. “It’s involved in synaptic plasticity,” she said. “That’s why the disabilities are worsening.”

Dr. Voskuhl supports a year-long, randomized and controlled study of estrogen supplementation in 150-200 participants. The goal, she said, is “not just to prevent loss and bad things from happening but also make improvements.”

In healthy patients, she said, outcomes should include cognitive decline in menopause, cognitive domain outcomes, and region-specific biomarkers in the frontal cortex and hippocampus instead of global cognition and global brain volume. In patients with MS, she said, the focus should be on worsening of disability with emphasis on specific disabilities such as walking and region-specific biomarkers for the motor cortex and spinal cord.

“We need to be looking at cortical gray matter, which we know is responsive to estrogen,” Dr. Voskuhl said. She led a 2018 placebo-controlled study that found women with MS who took estrogen supplements appeared to experience localized sparing of progressive gray matter, which the researchers linked to improved results in cognitive testing. The findings, the study authors wrote, suggest “a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.”

What about men? Does hormone loss worsen their MS? Dr. Voskuhl said there seems to be a connection between lower levels of testosterone and more disability in men with MS. But their situation is different. Loss of testosterone in men is gradual and happens over decades instead of over the short period of menopause in women, she said.

Jennifer Graves, MD, a neurologist at the University of California, San Diego, agreed that it’s time for further research into estrogen supplementation in MS. As she noted, “we don’t know the exact biological mechanism that might link perimenopause with developing a more progressive type of MS.”

She added: “An overall decrease in estrogen may be at play but there are other biological changes around menopause. We must also take care in studies to try to separate out what might be due to ovarian aging versus other types of aging processes that might be happening at the same time.”

Dr. Voskuhl disclosed that she is an inventor on university patents for use of estriol and estrogen receptor–beta ligands as treatments. Dr. Graves reports no relevant disclosures.

Children who have higher levels of sun exposure appear to have a substantially lower risk of developing pediatric multiple sclerosis (MS) than children who are less exposed to the sun, research shows. The use of sunscreen does not appear to affect the risk.

“This is the first study, as far as we are aware, to investigate the effect of sun exposure in pediatric MS,” first author Prince Sebastian, of the ANU Medical School, Australian National University, Canberra, said during a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“In order to reduce the incidence of MS, parents should be encouraged to allow their children to spend at least 30 minutes outdoors in the sun every day, while using adequate sun protection,” Mr. Sebastian said.

“This is especially important for children with a family history of MS,” he said. As the findings show, “you can use adequate sun protection and still get the benefit of sun exposure in terms of MS risk reduction.”

Low sun exposure, exposure to ultraviolet light, and vitamin D have been well established as modifiable risk factors for MS in adults. However, research is lacking on the effect of these factors upon patients younger than 18 years who have pediatric MS, a less common form of the disease. Pediatric MS constitutes about 5% of all MS cases.

To investigate the issue, Mr. Sebastian and colleagues evaluated data on 332 patients with pediatric MS who were between the ages of 4 and 22 years. The patients were enrolled at 16 MS centers around the United States. They were compared by sex and age with 534 control persons aged 3-22 years who did not have MS.

For the patients with MS, the median disease duration was 7.3 months, and 63% were female. The median age of the patients was 15.9 years.

Compared with those who did not have MS, patients with MS were significantly less likely to have been exposed to cigarette smoke (17.8% vs. 14.2%). They were significantly more likely to be overweight (23.8% vs. 14.2%), and the median anti-VCA level was higher (3.7 vs. 2.2).

Those who were exposed to the sun during the most recent summer for a duration of 30 minutes to 1 hour daily, as determined on the basis of self-report or parent report, had a 2.6-fold reduced risk of having MS, compared with those who spent less than 30 minutes outdoors daily (odds ratio, 0.39; P < .05), after adjusting for age, sex, birth season, the child’s skin color, the mother’s education, smoke exposure, being overweight, and Epstein-Barr virus infection.

Sun exposure for 1-2 hours daily was associated with a 7.4-fold reduced risk for MS, compared with exposure of 30 minutes or less (OR, 0.13; P < .001).

The odds were similar for those with 2-3 hours of sun exposure (OR, 0.21; P < .001) and for those with more than 3 hours of daily exposure (OR, 0.14; P < .001), versus less than 30 minutes.

Mr. Sebastian and his team also assessed the role of summer ambient levels of UV light and whether such exposure conferred a similar degree of protection. The risk for MS was lower among those who were exposed to higher summer ambient UV levels than among those exposed to lower levels (OR, 0.80; P = .046).

He noted, “Based on the results, individuals residing in Florida (28° N) would have 20% lower odds of MS, compared with an individual residing in New York (40° N).”

Interestingly, median rates of the use of sun protection were similar for the participants with MS and those without MS (OR, 0.95), suggesting that the use of sunscreen did not reduce the protective effect of sun exposure.

“We predicted that greater use of protection would limit effective sun exposure and would therefore increase MS risk,” Mr. Sebastian said, “but we don’t see that, and it’s probably because someone who uses sun protection likely gets more sun exposure anyway.”

“Our results suggest that you can use adequate sun protection and still get most of the benefit in terms of MS prevention, which is quite encouraging,” he added.

For those with MS, median serum 25(OH)D levels were higher (27.7 ng/mL vs. 23.7 ng/mL; P < .001), but Mr. Sebastian noted that this difference was likely attributable to the use of vitamin D supplementation after an MS diagnosis. An important limitation of the study was a lack of data on supplementation.
 

Stronger effect of frequent sun protection

Previous studies have shown a link between sun exposure and MS. A study published in 2018 compared 2,251 patients with MS with 4,028 control persons who did not have MS. The participants were in Canada, Italy, and Norway.

In that study, for most of the patients with MS, the age of onset was older than 18 years. In that study, there was a nearly 50% increased risk among those with the lowest degree of summer sun exposure in comparison with those who had the highest level of exposure (risk ratio, 1.47).

Contrary to the current study, that study did show an effect of the use of sun protection – those with the lowest degree of sun exposure during summer and winter and the highest use of sun protection had the highest risk for MS. They had a 76% increased risk, compared with those who had the highest degree of sun exposure and the least use of sun protection (RR, 1.76).

Sandra Magalhaes, PhD, of the University of New Brunswick, Fredericton, Canada, who was first author on that study, noted that the new study of pediatric MS adds valuable evidence on the issue.

“This study is important, as it adds to the etiological literature on MS implicating relevance of sun exposure,” Dr. Magalhaes said.

“We have a number of studies that have demonstrated an important effect of reduced levels of sun exposure and increased risk of MS. However, these studies focus on adult-onset MS populations; rather, the new study adds to the existing literature, as it also implicates sun exposure in etiology of pediatric-onset MS,” she said.

Notably, their previous work, unlike the current study, showed that, among those who experienced low levels of sun exposure, the risk for MS was higher for those who used sunscreen frequently.

“Overall, in their limited time outdoors, use of sunscreen may further increase risk of MS, which makes sense, since limited time outdoors in less sun, adding sun protection means [exposure to] even less sun.”

The findings of both studies support the bulk of research indicating that sun exposure is beneficial with regard to MS.

“There is a need for promoting balanced safe sun practices to reduce disease burden, especially in countries and cultures where children spend a lot of time indoors,” Dr. Magalhaes said. “Sun exposure has a number of important physiological roles, including vitamin D synthesis but also immune system functioning.”

Mr. Sebastian and Dr. Magalhaes have disclosed no relevant financial relationships.

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

Children who have higher levels of sun exposure appear to have a substantially lower risk of developing pediatric multiple sclerosis (MS) than children who are less exposed to the sun, research shows. The use of sunscreen does not appear to affect the risk.

“This is the first study, as far as we are aware, to investigate the effect of sun exposure in pediatric MS,” first author Prince Sebastian, of the ANU Medical School, Australian National University, Canberra, said during a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“In order to reduce the incidence of MS, parents should be encouraged to allow their children to spend at least 30 minutes outdoors in the sun every day, while using adequate sun protection,” Mr. Sebastian said.

“This is especially important for children with a family history of MS,” he said. As the findings show, “you can use adequate sun protection and still get the benefit of sun exposure in terms of MS risk reduction.”

Low sun exposure, exposure to ultraviolet light, and vitamin D have been well established as modifiable risk factors for MS in adults. However, research is lacking on the effect of these factors upon patients younger than 18 years who have pediatric MS, a less common form of the disease. Pediatric MS constitutes about 5% of all MS cases.

To investigate the issue, Mr. Sebastian and colleagues evaluated data on 332 patients with pediatric MS who were between the ages of 4 and 22 years. The patients were enrolled at 16 MS centers around the United States. They were compared by sex and age with 534 control persons aged 3-22 years who did not have MS.

For the patients with MS, the median disease duration was 7.3 months, and 63% were female. The median age of the patients was 15.9 years.

Compared with those who did not have MS, patients with MS were significantly less likely to have been exposed to cigarette smoke (17.8% vs. 14.2%). They were significantly more likely to be overweight (23.8% vs. 14.2%), and the median anti-VCA level was higher (3.7 vs. 2.2).

Those who were exposed to the sun during the most recent summer for a duration of 30 minutes to 1 hour daily, as determined on the basis of self-report or parent report, had a 2.6-fold reduced risk of having MS, compared with those who spent less than 30 minutes outdoors daily (odds ratio, 0.39; P < .05), after adjusting for age, sex, birth season, the child’s skin color, the mother’s education, smoke exposure, being overweight, and Epstein-Barr virus infection.

Sun exposure for 1-2 hours daily was associated with a 7.4-fold reduced risk for MS, compared with exposure of 30 minutes or less (OR, 0.13; P < .001).

The odds were similar for those with 2-3 hours of sun exposure (OR, 0.21; P < .001) and for those with more than 3 hours of daily exposure (OR, 0.14; P < .001), versus less than 30 minutes.

Mr. Sebastian and his team also assessed the role of summer ambient levels of UV light and whether such exposure conferred a similar degree of protection. The risk for MS was lower among those who were exposed to higher summer ambient UV levels than among those exposed to lower levels (OR, 0.80; P = .046).

He noted, “Based on the results, individuals residing in Florida (28° N) would have 20% lower odds of MS, compared with an individual residing in New York (40° N).”

Interestingly, median rates of the use of sun protection were similar for the participants with MS and those without MS (OR, 0.95), suggesting that the use of sunscreen did not reduce the protective effect of sun exposure.

“We predicted that greater use of protection would limit effective sun exposure and would therefore increase MS risk,” Mr. Sebastian said, “but we don’t see that, and it’s probably because someone who uses sun protection likely gets more sun exposure anyway.”

“Our results suggest that you can use adequate sun protection and still get most of the benefit in terms of MS prevention, which is quite encouraging,” he added.

For those with MS, median serum 25(OH)D levels were higher (27.7 ng/mL vs. 23.7 ng/mL; P < .001), but Mr. Sebastian noted that this difference was likely attributable to the use of vitamin D supplementation after an MS diagnosis. An important limitation of the study was a lack of data on supplementation.
 

Stronger effect of frequent sun protection

Previous studies have shown a link between sun exposure and MS. A study published in 2018 compared 2,251 patients with MS with 4,028 control persons who did not have MS. The participants were in Canada, Italy, and Norway.

In that study, for most of the patients with MS, the age of onset was older than 18 years. In that study, there was a nearly 50% increased risk among those with the lowest degree of summer sun exposure in comparison with those who had the highest level of exposure (risk ratio, 1.47).

Contrary to the current study, that study did show an effect of the use of sun protection – those with the lowest degree of sun exposure during summer and winter and the highest use of sun protection had the highest risk for MS. They had a 76% increased risk, compared with those who had the highest degree of sun exposure and the least use of sun protection (RR, 1.76).

Sandra Magalhaes, PhD, of the University of New Brunswick, Fredericton, Canada, who was first author on that study, noted that the new study of pediatric MS adds valuable evidence on the issue.

“This study is important, as it adds to the etiological literature on MS implicating relevance of sun exposure,” Dr. Magalhaes said.

“We have a number of studies that have demonstrated an important effect of reduced levels of sun exposure and increased risk of MS. However, these studies focus on adult-onset MS populations; rather, the new study adds to the existing literature, as it also implicates sun exposure in etiology of pediatric-onset MS,” she said.

Notably, their previous work, unlike the current study, showed that, among those who experienced low levels of sun exposure, the risk for MS was higher for those who used sunscreen frequently.

“Overall, in their limited time outdoors, use of sunscreen may further increase risk of MS, which makes sense, since limited time outdoors in less sun, adding sun protection means [exposure to] even less sun.”

The findings of both studies support the bulk of research indicating that sun exposure is beneficial with regard to MS.

“There is a need for promoting balanced safe sun practices to reduce disease burden, especially in countries and cultures where children spend a lot of time indoors,” Dr. Magalhaes said. “Sun exposure has a number of important physiological roles, including vitamin D synthesis but also immune system functioning.”

Mr. Sebastian and Dr. Magalhaes have disclosed no relevant financial relationships.

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

Children who have higher levels of sun exposure appear to have a substantially lower risk of developing pediatric multiple sclerosis (MS) than children who are less exposed to the sun, research shows. The use of sunscreen does not appear to affect the risk.

“This is the first study, as far as we are aware, to investigate the effect of sun exposure in pediatric MS,” first author Prince Sebastian, of the ANU Medical School, Australian National University, Canberra, said during a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“In order to reduce the incidence of MS, parents should be encouraged to allow their children to spend at least 30 minutes outdoors in the sun every day, while using adequate sun protection,” Mr. Sebastian said.

“This is especially important for children with a family history of MS,” he said. As the findings show, “you can use adequate sun protection and still get the benefit of sun exposure in terms of MS risk reduction.”

Low sun exposure, exposure to ultraviolet light, and vitamin D have been well established as modifiable risk factors for MS in adults. However, research is lacking on the effect of these factors upon patients younger than 18 years who have pediatric MS, a less common form of the disease. Pediatric MS constitutes about 5% of all MS cases.

To investigate the issue, Mr. Sebastian and colleagues evaluated data on 332 patients with pediatric MS who were between the ages of 4 and 22 years. The patients were enrolled at 16 MS centers around the United States. They were compared by sex and age with 534 control persons aged 3-22 years who did not have MS.

For the patients with MS, the median disease duration was 7.3 months, and 63% were female. The median age of the patients was 15.9 years.

Compared with those who did not have MS, patients with MS were significantly less likely to have been exposed to cigarette smoke (17.8% vs. 14.2%). They were significantly more likely to be overweight (23.8% vs. 14.2%), and the median anti-VCA level was higher (3.7 vs. 2.2).

Those who were exposed to the sun during the most recent summer for a duration of 30 minutes to 1 hour daily, as determined on the basis of self-report or parent report, had a 2.6-fold reduced risk of having MS, compared with those who spent less than 30 minutes outdoors daily (odds ratio, 0.39; P < .05), after adjusting for age, sex, birth season, the child’s skin color, the mother’s education, smoke exposure, being overweight, and Epstein-Barr virus infection.

Sun exposure for 1-2 hours daily was associated with a 7.4-fold reduced risk for MS, compared with exposure of 30 minutes or less (OR, 0.13; P < .001).

The odds were similar for those with 2-3 hours of sun exposure (OR, 0.21; P < .001) and for those with more than 3 hours of daily exposure (OR, 0.14; P < .001), versus less than 30 minutes.

Mr. Sebastian and his team also assessed the role of summer ambient levels of UV light and whether such exposure conferred a similar degree of protection. The risk for MS was lower among those who were exposed to higher summer ambient UV levels than among those exposed to lower levels (OR, 0.80; P = .046).

He noted, “Based on the results, individuals residing in Florida (28° N) would have 20% lower odds of MS, compared with an individual residing in New York (40° N).”

Interestingly, median rates of the use of sun protection were similar for the participants with MS and those without MS (OR, 0.95), suggesting that the use of sunscreen did not reduce the protective effect of sun exposure.

“We predicted that greater use of protection would limit effective sun exposure and would therefore increase MS risk,” Mr. Sebastian said, “but we don’t see that, and it’s probably because someone who uses sun protection likely gets more sun exposure anyway.”

“Our results suggest that you can use adequate sun protection and still get most of the benefit in terms of MS prevention, which is quite encouraging,” he added.

For those with MS, median serum 25(OH)D levels were higher (27.7 ng/mL vs. 23.7 ng/mL; P < .001), but Mr. Sebastian noted that this difference was likely attributable to the use of vitamin D supplementation after an MS diagnosis. An important limitation of the study was a lack of data on supplementation.
 

Stronger effect of frequent sun protection

Previous studies have shown a link between sun exposure and MS. A study published in 2018 compared 2,251 patients with MS with 4,028 control persons who did not have MS. The participants were in Canada, Italy, and Norway.

In that study, for most of the patients with MS, the age of onset was older than 18 years. In that study, there was a nearly 50% increased risk among those with the lowest degree of summer sun exposure in comparison with those who had the highest level of exposure (risk ratio, 1.47).

Contrary to the current study, that study did show an effect of the use of sun protection – those with the lowest degree of sun exposure during summer and winter and the highest use of sun protection had the highest risk for MS. They had a 76% increased risk, compared with those who had the highest degree of sun exposure and the least use of sun protection (RR, 1.76).

Sandra Magalhaes, PhD, of the University of New Brunswick, Fredericton, Canada, who was first author on that study, noted that the new study of pediatric MS adds valuable evidence on the issue.

“This study is important, as it adds to the etiological literature on MS implicating relevance of sun exposure,” Dr. Magalhaes said.

“We have a number of studies that have demonstrated an important effect of reduced levels of sun exposure and increased risk of MS. However, these studies focus on adult-onset MS populations; rather, the new study adds to the existing literature, as it also implicates sun exposure in etiology of pediatric-onset MS,” she said.

Notably, their previous work, unlike the current study, showed that, among those who experienced low levels of sun exposure, the risk for MS was higher for those who used sunscreen frequently.

“Overall, in their limited time outdoors, use of sunscreen may further increase risk of MS, which makes sense, since limited time outdoors in less sun, adding sun protection means [exposure to] even less sun.”

The findings of both studies support the bulk of research indicating that sun exposure is beneficial with regard to MS.

“There is a need for promoting balanced safe sun practices to reduce disease burden, especially in countries and cultures where children spend a lot of time indoors,” Dr. Magalhaes said. “Sun exposure has a number of important physiological roles, including vitamin D synthesis but also immune system functioning.”

Mr. Sebastian and Dr. Magalhaes have disclosed no relevant financial relationships.

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

Erythropoietin (EPO), shown in early studies to potentially provide neuroprotection for patients with optic neuritis, failed to provide any significant neuroprotection in comparison with placebo in a phase 3 randomized controlled trial.

“EPO conveyed neither functional nor structural neuroprotection in the visual pathways after optic neuritis as a clinically isolated syndrome,” said first author Wolf A. Lagreze, MD, of the University of Freiburg (Germany), in presenting the results at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

There are currently no treatments that provide neuroprotection for patients with optic neuritis, which can result in the degeneration of retinal ganglion cells, the axons of which form the optic nerve.

Although methylprednisolone, the standard treatment, can be of benefit, it has no effect in preventing neurodegeneration or subsequent vision impairment.

Importantly, optic neuritis, which can be a first sign of multiple sclerosis (MS), is considered an ideal model for an acute inflammatory attack on the nervous system and resulting neurodegeneration. Therefore, any treatment that provides neuroprotection for patients with optic neuritis could have potentially exciting broader implications.
 

The TONE trial

Preclinical studies have shown that EPO provides a small, potential degree of neuroprotection. To further evaluate EPO in this setting, Dr. Lagreze and colleagues conducted the TONE trial (Treatment of Optic Neuritis With Erythropoietin) in Germany between 2014 and 2017, in which they enrolled 108 patients with optic neuritis.

Inclusion criteria were having only unilateral optic neuritis as a clinically isolated syndrome that presented within 10 days of the first symptoms and having moderate to severe loss of visual acuity.

Persons with known MS were excluded; however, patients who were diagnosed with MS at the beginning of the study during the workup evaluation were included. Hence, about 20% of patients did have newly diagnosed MS, Dr. Lagreze noted.

The participants were randomly assigned in double-blind 1:1 ratio to receive treatment with either 33,000 IU EPO or placebo intravenously for 3 days as an adjunct to high-dose intravenous methylprednisolone (1,000 mg/day).

The final analysis included 52 patients who received EPO and 51 patients who received placebo. There were no significant differences between the groups in the first primary outcome of retinal nerve fiber layer atrophy, assessed with optic coherence tomography at week 26 (P = .76).

Likewise, no significant difference between groups was observed in the second primary outcome of low-contrast visual acuity at week 26, assessed using the 2.5% Sloan chart score of the affected eye (P = .38).

In addition, there were no significant differences between the groups in the rates of optic neuritis relapse.

In terms of safety measures, one patient in the EPO group developed sinus venous thrombosis, which was treated with anticoagulants and resolved without complications.
 

Reduced conversion to MS?

Interestingly, after 6 months, significantly fewer patients in the EPO arm (36%) had converted from clinically isolated syndrome to MS, compared with 57% in the placebo arm (P = .032). The difference became apparent as early as week 4.

Although those findings suggest that EPO provided some neuroprotection, there are notable caveats, Philippe Albrecht, MD, of the department of neurology at the University Hospital Dusseldorf (Germany), and a coauthor on the study, said.

“The significant separation of EPO and placebo group regarding MS conversion was observed very early on in the course and did not change thereafter,” Dr. Albrecht noted.

“One would expect a true disease-modifying effect of EPO on MS conversion to take longer to develop, and this early separation may very well have been due to an imbalance in the treatment groups, [for example] regarding MRI imaging findings such as gadolinium enhancement at baseline,” he said.

Dr. Lagreze said that it was a surprise to see no benefit from the drug, and a closer look at certain subgroups may still be worthwhile. Factors that could have a bearing on results include a shorter time interval for inclusion, having no concomitant use of steroids, and longer duration of treatment with EPO.

“If I could do the study again, I would do the treatment for longer than 3 days – that was based on experiences in previous EPO trials,” he said. “I would also love to do the trial without the concomitant methylprednisolone, but that is not possible from an ethical point of view.”
 

Trial nevertheless important

Commenting on the study, E. Anne Yeh, MD, of the division of neurology at the Hospital for Sick Children, Toronto, agreed that a challenge in evaluating therapies for optic neuritis is the potential for confounding from existing therapies that patients need to take.

“This agent could not be evaluated alone for its protective effect in comparison to no treatment at all,” she said.

In addition, improved metrics for gauging outcomes are needed to better determine the true effects, she added.

“The development of newer vision-related outcome metrics is important for future studies, and many are hard at work on both structural and functional metrics that may help us to understand the benefits of any protective therapies in a more nuanced manner than we are currently able to,” she said.

However, results of any kind – negative or positive – are valuable in improving understanding, Dr. Yeh underscored.

“Negative results can be disappointing in any trial, especially one in which alternative therapeutic pathways are being sought,” Dr. Yeh said. “I want to emphasize, however, that the fact that we are even considering and completing trials in this area is important.”

Dr. Yeh noted that she is currently involved in a trial that is evaluating the diabetes drug metformin for its remyelinating potential. “We hope to have some pilot data on MS in a few years,” she said.

Dr. Lagreze, Dr. Albrecht, and Dr. Yeh have disclosed no relevant financial relationships.

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

Erythropoietin (EPO), shown in early studies to potentially provide neuroprotection for patients with optic neuritis, failed to provide any significant neuroprotection in comparison with placebo in a phase 3 randomized controlled trial.

“EPO conveyed neither functional nor structural neuroprotection in the visual pathways after optic neuritis as a clinically isolated syndrome,” said first author Wolf A. Lagreze, MD, of the University of Freiburg (Germany), in presenting the results at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

There are currently no treatments that provide neuroprotection for patients with optic neuritis, which can result in the degeneration of retinal ganglion cells, the axons of which form the optic nerve.

Although methylprednisolone, the standard treatment, can be of benefit, it has no effect in preventing neurodegeneration or subsequent vision impairment.

Importantly, optic neuritis, which can be a first sign of multiple sclerosis (MS), is considered an ideal model for an acute inflammatory attack on the nervous system and resulting neurodegeneration. Therefore, any treatment that provides neuroprotection for patients with optic neuritis could have potentially exciting broader implications.
 

The TONE trial

Preclinical studies have shown that EPO provides a small, potential degree of neuroprotection. To further evaluate EPO in this setting, Dr. Lagreze and colleagues conducted the TONE trial (Treatment of Optic Neuritis With Erythropoietin) in Germany between 2014 and 2017, in which they enrolled 108 patients with optic neuritis.

Inclusion criteria were having only unilateral optic neuritis as a clinically isolated syndrome that presented within 10 days of the first symptoms and having moderate to severe loss of visual acuity.

Persons with known MS were excluded; however, patients who were diagnosed with MS at the beginning of the study during the workup evaluation were included. Hence, about 20% of patients did have newly diagnosed MS, Dr. Lagreze noted.

The participants were randomly assigned in double-blind 1:1 ratio to receive treatment with either 33,000 IU EPO or placebo intravenously for 3 days as an adjunct to high-dose intravenous methylprednisolone (1,000 mg/day).

The final analysis included 52 patients who received EPO and 51 patients who received placebo. There were no significant differences between the groups in the first primary outcome of retinal nerve fiber layer atrophy, assessed with optic coherence tomography at week 26 (P = .76).

Likewise, no significant difference between groups was observed in the second primary outcome of low-contrast visual acuity at week 26, assessed using the 2.5% Sloan chart score of the affected eye (P = .38).

In addition, there were no significant differences between the groups in the rates of optic neuritis relapse.

In terms of safety measures, one patient in the EPO group developed sinus venous thrombosis, which was treated with anticoagulants and resolved without complications.
 

Reduced conversion to MS?

Interestingly, after 6 months, significantly fewer patients in the EPO arm (36%) had converted from clinically isolated syndrome to MS, compared with 57% in the placebo arm (P = .032). The difference became apparent as early as week 4.

Although those findings suggest that EPO provided some neuroprotection, there are notable caveats, Philippe Albrecht, MD, of the department of neurology at the University Hospital Dusseldorf (Germany), and a coauthor on the study, said.

“The significant separation of EPO and placebo group regarding MS conversion was observed very early on in the course and did not change thereafter,” Dr. Albrecht noted.

“One would expect a true disease-modifying effect of EPO on MS conversion to take longer to develop, and this early separation may very well have been due to an imbalance in the treatment groups, [for example] regarding MRI imaging findings such as gadolinium enhancement at baseline,” he said.

Dr. Lagreze said that it was a surprise to see no benefit from the drug, and a closer look at certain subgroups may still be worthwhile. Factors that could have a bearing on results include a shorter time interval for inclusion, having no concomitant use of steroids, and longer duration of treatment with EPO.

“If I could do the study again, I would do the treatment for longer than 3 days – that was based on experiences in previous EPO trials,” he said. “I would also love to do the trial without the concomitant methylprednisolone, but that is not possible from an ethical point of view.”
 

Trial nevertheless important

Commenting on the study, E. Anne Yeh, MD, of the division of neurology at the Hospital for Sick Children, Toronto, agreed that a challenge in evaluating therapies for optic neuritis is the potential for confounding from existing therapies that patients need to take.

“This agent could not be evaluated alone for its protective effect in comparison to no treatment at all,” she said.

In addition, improved metrics for gauging outcomes are needed to better determine the true effects, she added.

“The development of newer vision-related outcome metrics is important for future studies, and many are hard at work on both structural and functional metrics that may help us to understand the benefits of any protective therapies in a more nuanced manner than we are currently able to,” she said.

However, results of any kind – negative or positive – are valuable in improving understanding, Dr. Yeh underscored.

“Negative results can be disappointing in any trial, especially one in which alternative therapeutic pathways are being sought,” Dr. Yeh said. “I want to emphasize, however, that the fact that we are even considering and completing trials in this area is important.”

Dr. Yeh noted that she is currently involved in a trial that is evaluating the diabetes drug metformin for its remyelinating potential. “We hope to have some pilot data on MS in a few years,” she said.

Dr. Lagreze, Dr. Albrecht, and Dr. Yeh have disclosed no relevant financial relationships.

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

Erythropoietin (EPO), shown in early studies to potentially provide neuroprotection for patients with optic neuritis, failed to provide any significant neuroprotection in comparison with placebo in a phase 3 randomized controlled trial.

“EPO conveyed neither functional nor structural neuroprotection in the visual pathways after optic neuritis as a clinically isolated syndrome,” said first author Wolf A. Lagreze, MD, of the University of Freiburg (Germany), in presenting the results at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

There are currently no treatments that provide neuroprotection for patients with optic neuritis, which can result in the degeneration of retinal ganglion cells, the axons of which form the optic nerve.

Although methylprednisolone, the standard treatment, can be of benefit, it has no effect in preventing neurodegeneration or subsequent vision impairment.

Importantly, optic neuritis, which can be a first sign of multiple sclerosis (MS), is considered an ideal model for an acute inflammatory attack on the nervous system and resulting neurodegeneration. Therefore, any treatment that provides neuroprotection for patients with optic neuritis could have potentially exciting broader implications.
 

The TONE trial

Preclinical studies have shown that EPO provides a small, potential degree of neuroprotection. To further evaluate EPO in this setting, Dr. Lagreze and colleagues conducted the TONE trial (Treatment of Optic Neuritis With Erythropoietin) in Germany between 2014 and 2017, in which they enrolled 108 patients with optic neuritis.

Inclusion criteria were having only unilateral optic neuritis as a clinically isolated syndrome that presented within 10 days of the first symptoms and having moderate to severe loss of visual acuity.

Persons with known MS were excluded; however, patients who were diagnosed with MS at the beginning of the study during the workup evaluation were included. Hence, about 20% of patients did have newly diagnosed MS, Dr. Lagreze noted.

The participants were randomly assigned in double-blind 1:1 ratio to receive treatment with either 33,000 IU EPO or placebo intravenously for 3 days as an adjunct to high-dose intravenous methylprednisolone (1,000 mg/day).

The final analysis included 52 patients who received EPO and 51 patients who received placebo. There were no significant differences between the groups in the first primary outcome of retinal nerve fiber layer atrophy, assessed with optic coherence tomography at week 26 (P = .76).

Likewise, no significant difference between groups was observed in the second primary outcome of low-contrast visual acuity at week 26, assessed using the 2.5% Sloan chart score of the affected eye (P = .38).

In addition, there were no significant differences between the groups in the rates of optic neuritis relapse.

In terms of safety measures, one patient in the EPO group developed sinus venous thrombosis, which was treated with anticoagulants and resolved without complications.
 

Reduced conversion to MS?

Interestingly, after 6 months, significantly fewer patients in the EPO arm (36%) had converted from clinically isolated syndrome to MS, compared with 57% in the placebo arm (P = .032). The difference became apparent as early as week 4.

Although those findings suggest that EPO provided some neuroprotection, there are notable caveats, Philippe Albrecht, MD, of the department of neurology at the University Hospital Dusseldorf (Germany), and a coauthor on the study, said.

“The significant separation of EPO and placebo group regarding MS conversion was observed very early on in the course and did not change thereafter,” Dr. Albrecht noted.

“One would expect a true disease-modifying effect of EPO on MS conversion to take longer to develop, and this early separation may very well have been due to an imbalance in the treatment groups, [for example] regarding MRI imaging findings such as gadolinium enhancement at baseline,” he said.

Dr. Lagreze said that it was a surprise to see no benefit from the drug, and a closer look at certain subgroups may still be worthwhile. Factors that could have a bearing on results include a shorter time interval for inclusion, having no concomitant use of steroids, and longer duration of treatment with EPO.

“If I could do the study again, I would do the treatment for longer than 3 days – that was based on experiences in previous EPO trials,” he said. “I would also love to do the trial without the concomitant methylprednisolone, but that is not possible from an ethical point of view.”
 

Trial nevertheless important

Commenting on the study, E. Anne Yeh, MD, of the division of neurology at the Hospital for Sick Children, Toronto, agreed that a challenge in evaluating therapies for optic neuritis is the potential for confounding from existing therapies that patients need to take.

“This agent could not be evaluated alone for its protective effect in comparison to no treatment at all,” she said.

In addition, improved metrics for gauging outcomes are needed to better determine the true effects, she added.

“The development of newer vision-related outcome metrics is important for future studies, and many are hard at work on both structural and functional metrics that may help us to understand the benefits of any protective therapies in a more nuanced manner than we are currently able to,” she said.

However, results of any kind – negative or positive – are valuable in improving understanding, Dr. Yeh underscored.

“Negative results can be disappointing in any trial, especially one in which alternative therapeutic pathways are being sought,” Dr. Yeh said. “I want to emphasize, however, that the fact that we are even considering and completing trials in this area is important.”

Dr. Yeh noted that she is currently involved in a trial that is evaluating the diabetes drug metformin for its remyelinating potential. “We hope to have some pilot data on MS in a few years,” she said.

Dr. Lagreze, Dr. Albrecht, and Dr. Yeh have disclosed no relevant financial relationships.

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

Multiple sclerosis (MS) affects Whites, African Americans, and Hispanics differently, a new study finds, and there are big gaps in how they respond to disease-modifying therapies (DMTs).

“Hispanics and African Americans develop a more severe disease course and accumulate more MS-related disability over time despite similar sociodemographic backgrounds and similar patterns of DMT use throughout their disease, suggesting that socioeconomic status and access to health care may not be the main determinants of health,” said neurologist Carlos Pérez, MD, of the University of Texas Health Science Center, Houston. He spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and in a follow-up interview.

“In addition,” Dr. Pérez said, “therapeutic responses to individual DMTs, as well as tolerance and side-effect profiles, are also variable among racial/ethnic groups.”

The researchers tracked 150 patients with MS at the University of Texas Health Science Center – 50 Whites, 50 African American, and 50 Hispanic – who were age and gender matched. The average age of the subjects was 45, and 74% of those in each group were women.

While educational levels between the groups were similar, African Americans had a much higher rate of lost employment because of disability (38%) than Hispanics (19%) and Whites (15%, P = .02). Fifty-seven patients (38%) needed escalation of therapy, and 63% were African American.

About 30% of subjects switched DMTs because of intolerance/adverse events, and 47% of those were African American. Interferons most commonly caused adverse effects in African Americans (61%), and Whites were the most likely to not tolerate glatiramer acetate (39%) than Hispanics (8%) and African Americans (13%).

What might be behind the disparities? “It is possible that genetic factors may play a greater role than previously thought. A recent study reported that Hispanic and African American patients with MS have higher levels of peripheral blood plasmablasts, which may provide indirect evidence for potential biological mechanisms underlying racial and clinical disparities in MS,” Dr. Pérez said. “These mechanisms appear to involve higher degrees of inflammation in the central nervous system. This may explain why African Americans may respond better to higher-efficacy therapies initially, when inflammatory processes predominate MS-related pathology, rather than at later stages of the disease when inflammation plays a less prominent role. Neurologists should consider higher-efficacy DMT as first line. We have begun to do this in our practice.”

Dr. Pérez said the findings offer other lessons. “Neurologists should consider that Caucasian patients tolerate glatiramer acetate less frequently, compared with other racial groups, and potentially consider using alternative DMTs unless the benefits outweigh the risks, such as during pregnancy.”

He also noted that African Americans treated with oral DMTs at baseline were more likely to develop worsening disability over time. “This argues in favor of infusion therapies as first-line treatment,” he said, adding that more Hispanics with MS were not on treatment – or discontinued treatment – compared with Whites and African Americans.
 

Close patient monitoring is key

Atlanta-area neurologist Mitzi Joi Williams, MD, who was asked to comment on the study findings, said in an interview that it “adds to the body of real-world evidence to assist understanding of MS in minority populations.”

She noted that African American patients who started on infusions appeared to be more stable. “There are a great deal of questions surrounding starting patients on injectables versus higher-efficacy therapy initially to prevent disability and this may lend credence to the need for closer examination of initial therapy for these patients. It is important to closely monitor patients and consider a switch in DMT if there is any clinical or radiologic progression, especially for African American and Hispanic patients since there is a great deal of data to suggest they may have more aggressive disease.”

Moving forward, more research like this is needed, she said. “Patients did all have insurance and were largely educated, but there could be other social determinants of health – i.e., transportation, lapses in insurance, or technology barriers – that may have led to worse outcomes.”

No study funding was reported, and Dr. Pérez reported no disclosures. Dr. Williams disclosed research support from EMD Serono, Genentech, and Novartis and advisory committee/consultant relationships with AbbVie, Biogen Idec, Bristol-Myers Squibb, EMD Serono, Genentech, Novartis, and Sanofi Genzyme.

Multiple sclerosis (MS) affects Whites, African Americans, and Hispanics differently, a new study finds, and there are big gaps in how they respond to disease-modifying therapies (DMTs).

“Hispanics and African Americans develop a more severe disease course and accumulate more MS-related disability over time despite similar sociodemographic backgrounds and similar patterns of DMT use throughout their disease, suggesting that socioeconomic status and access to health care may not be the main determinants of health,” said neurologist Carlos Pérez, MD, of the University of Texas Health Science Center, Houston. He spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and in a follow-up interview.

“In addition,” Dr. Pérez said, “therapeutic responses to individual DMTs, as well as tolerance and side-effect profiles, are also variable among racial/ethnic groups.”

The researchers tracked 150 patients with MS at the University of Texas Health Science Center – 50 Whites, 50 African American, and 50 Hispanic – who were age and gender matched. The average age of the subjects was 45, and 74% of those in each group were women.

While educational levels between the groups were similar, African Americans had a much higher rate of lost employment because of disability (38%) than Hispanics (19%) and Whites (15%, P = .02). Fifty-seven patients (38%) needed escalation of therapy, and 63% were African American.

About 30% of subjects switched DMTs because of intolerance/adverse events, and 47% of those were African American. Interferons most commonly caused adverse effects in African Americans (61%), and Whites were the most likely to not tolerate glatiramer acetate (39%) than Hispanics (8%) and African Americans (13%).

What might be behind the disparities? “It is possible that genetic factors may play a greater role than previously thought. A recent study reported that Hispanic and African American patients with MS have higher levels of peripheral blood plasmablasts, which may provide indirect evidence for potential biological mechanisms underlying racial and clinical disparities in MS,” Dr. Pérez said. “These mechanisms appear to involve higher degrees of inflammation in the central nervous system. This may explain why African Americans may respond better to higher-efficacy therapies initially, when inflammatory processes predominate MS-related pathology, rather than at later stages of the disease when inflammation plays a less prominent role. Neurologists should consider higher-efficacy DMT as first line. We have begun to do this in our practice.”

Dr. Pérez said the findings offer other lessons. “Neurologists should consider that Caucasian patients tolerate glatiramer acetate less frequently, compared with other racial groups, and potentially consider using alternative DMTs unless the benefits outweigh the risks, such as during pregnancy.”

He also noted that African Americans treated with oral DMTs at baseline were more likely to develop worsening disability over time. “This argues in favor of infusion therapies as first-line treatment,” he said, adding that more Hispanics with MS were not on treatment – or discontinued treatment – compared with Whites and African Americans.
 

Close patient monitoring is key

Atlanta-area neurologist Mitzi Joi Williams, MD, who was asked to comment on the study findings, said in an interview that it “adds to the body of real-world evidence to assist understanding of MS in minority populations.”

She noted that African American patients who started on infusions appeared to be more stable. “There are a great deal of questions surrounding starting patients on injectables versus higher-efficacy therapy initially to prevent disability and this may lend credence to the need for closer examination of initial therapy for these patients. It is important to closely monitor patients and consider a switch in DMT if there is any clinical or radiologic progression, especially for African American and Hispanic patients since there is a great deal of data to suggest they may have more aggressive disease.”

Moving forward, more research like this is needed, she said. “Patients did all have insurance and were largely educated, but there could be other social determinants of health – i.e., transportation, lapses in insurance, or technology barriers – that may have led to worse outcomes.”

No study funding was reported, and Dr. Pérez reported no disclosures. Dr. Williams disclosed research support from EMD Serono, Genentech, and Novartis and advisory committee/consultant relationships with AbbVie, Biogen Idec, Bristol-Myers Squibb, EMD Serono, Genentech, Novartis, and Sanofi Genzyme.

Multiple sclerosis (MS) affects Whites, African Americans, and Hispanics differently, a new study finds, and there are big gaps in how they respond to disease-modifying therapies (DMTs).

“Hispanics and African Americans develop a more severe disease course and accumulate more MS-related disability over time despite similar sociodemographic backgrounds and similar patterns of DMT use throughout their disease, suggesting that socioeconomic status and access to health care may not be the main determinants of health,” said neurologist Carlos Pérez, MD, of the University of Texas Health Science Center, Houston. He spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and in a follow-up interview.

“In addition,” Dr. Pérez said, “therapeutic responses to individual DMTs, as well as tolerance and side-effect profiles, are also variable among racial/ethnic groups.”

The researchers tracked 150 patients with MS at the University of Texas Health Science Center – 50 Whites, 50 African American, and 50 Hispanic – who were age and gender matched. The average age of the subjects was 45, and 74% of those in each group were women.

While educational levels between the groups were similar, African Americans had a much higher rate of lost employment because of disability (38%) than Hispanics (19%) and Whites (15%, P = .02). Fifty-seven patients (38%) needed escalation of therapy, and 63% were African American.

About 30% of subjects switched DMTs because of intolerance/adverse events, and 47% of those were African American. Interferons most commonly caused adverse effects in African Americans (61%), and Whites were the most likely to not tolerate glatiramer acetate (39%) than Hispanics (8%) and African Americans (13%).

What might be behind the disparities? “It is possible that genetic factors may play a greater role than previously thought. A recent study reported that Hispanic and African American patients with MS have higher levels of peripheral blood plasmablasts, which may provide indirect evidence for potential biological mechanisms underlying racial and clinical disparities in MS,” Dr. Pérez said. “These mechanisms appear to involve higher degrees of inflammation in the central nervous system. This may explain why African Americans may respond better to higher-efficacy therapies initially, when inflammatory processes predominate MS-related pathology, rather than at later stages of the disease when inflammation plays a less prominent role. Neurologists should consider higher-efficacy DMT as first line. We have begun to do this in our practice.”

Dr. Pérez said the findings offer other lessons. “Neurologists should consider that Caucasian patients tolerate glatiramer acetate less frequently, compared with other racial groups, and potentially consider using alternative DMTs unless the benefits outweigh the risks, such as during pregnancy.”

He also noted that African Americans treated with oral DMTs at baseline were more likely to develop worsening disability over time. “This argues in favor of infusion therapies as first-line treatment,” he said, adding that more Hispanics with MS were not on treatment – or discontinued treatment – compared with Whites and African Americans.
 

Close patient monitoring is key

Atlanta-area neurologist Mitzi Joi Williams, MD, who was asked to comment on the study findings, said in an interview that it “adds to the body of real-world evidence to assist understanding of MS in minority populations.”

She noted that African American patients who started on infusions appeared to be more stable. “There are a great deal of questions surrounding starting patients on injectables versus higher-efficacy therapy initially to prevent disability and this may lend credence to the need for closer examination of initial therapy for these patients. It is important to closely monitor patients and consider a switch in DMT if there is any clinical or radiologic progression, especially for African American and Hispanic patients since there is a great deal of data to suggest they may have more aggressive disease.”

Moving forward, more research like this is needed, she said. “Patients did all have insurance and were largely educated, but there could be other social determinants of health – i.e., transportation, lapses in insurance, or technology barriers – that may have led to worse outcomes.”

No study funding was reported, and Dr. Pérez reported no disclosures. Dr. Williams disclosed research support from EMD Serono, Genentech, and Novartis and advisory committee/consultant relationships with AbbVie, Biogen Idec, Bristol-Myers Squibb, EMD Serono, Genentech, Novartis, and Sanofi Genzyme.

While they’re extraordinarily expensive, a trio of newly approved medications is providing a variety of effective treatment options for patients with neuromyelitis optica spectrum disorder (NMOSD), a neurologist told colleagues.

“Patients have a choice of different options with different types of action. It’s good news,” said Sean J. Pittock, MD, of the Mayo Clinic in Rochester, Minn. “If you don’t stop the clinical attacks, patients can become very disabled very quickly. These medications have a significant impact in reducing the likelihood of having a clinical relapse. If you can stop the relapses, you certainly can eventually stop most – if not all – of the disability accrual.”

Dr. Pittock spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and answered follow-up questions in an interview.
 

Treatment advances for NMOSD

NMOSD, also known as NMO, is a relapsing autoimmune inflammatory disorder that causes recurrent optic neuritis and myelitis. It’s a rare disease, affecting 0.5-10 people per 100,000, mostly women.

Several recent trials have supported the use of the drugs eculizumab (Soliris), satralizumab (Enspryng) and inebilizumab (Uplizna) in NMOSD, Dr. Pittock said, and all have received Food and Drug Administration approval to treat the condition over the past 2 years. Dr. Pittock led the PREVENT trial of eculizumab, which showed a 94% reduction of relapse risk versus placebo.

The newly approved drugs are stunningly expensive. According to Dr. Pittock, eculizumab costs $710,000 a year, while inebilizumab runs $393,000 the first year, then $262,000 a year. Satralizumab is $219,000 the first year, then $190,000 a year. Assistance programs are available, Dr. Pittock said, “and we’ve not had any major problems in terms of initiation.”

The cost of rituximab (Rituxan), which has a history of use as an off-label treatment option, is $18,000 a year and dropping, according to Dr. Pittock. There’s also new research on rituximab: In 2020, a small Japanese trial (n = 38) reported prevention of relapses compared with placebo, but Dr. Pittock cautioned that “the placebo patients seem to have a more benign course or more benign phenotypes” than the intervention group.

“There’s no doubt that rituximab works, but does it work as well as the other medications that have been through more of a robust trial process?” he asked. Keep in mind, he added, that perhaps 20%-50% of patients will relapse on rituximab.

Dr. Pittock advised colleagues to consider factors like patient schedules and compliance when choosing a drug. Satralizumab is self-administered monthly, while inebilizumab and rituximab are infused every 6 months.
 

Progress in anti-MOG disease

The trials in NMOSD should spur studies of the drugs in anti–myelin oligodendrocyte glycoprotein (MOG) disease, he said. “I think we’ll see a more rapid move toward phase 3 trials because of the experience with NMO. We will just have to wait and see which medications enter trial.”

Anti-MOG disease, also known as MOG antibody disease (MOGAD) and anti-MOG–associated encephalomyelitis, is caused by anti-MOG antibodies. Optic neuritis is very common, and transverse myelitis can occur.

The condition “actually responds to different drugs than MS and has a different immune pathophysiology,” Dr. Pittock said.

He cautioned colleagues to be aware that “the ability of the antibody to tell you whether or not the patient has the disease is less clear for MOGAD than it is for other diseases. If your patient has a low titer of MOG antibody, and their phenotype really doesn’t look like [MOGAD], you really need to interpret that with significant caution.”

He also highlighted a 2018 report that offers guidance about diagnosis and when MOG-IgC antibody tests are appropriate in CNS demyelinating disease.

Dr. Pittock reported numerous disclosures plus patents issued or pending.

While they’re extraordinarily expensive, a trio of newly approved medications is providing a variety of effective treatment options for patients with neuromyelitis optica spectrum disorder (NMOSD), a neurologist told colleagues.

“Patients have a choice of different options with different types of action. It’s good news,” said Sean J. Pittock, MD, of the Mayo Clinic in Rochester, Minn. “If you don’t stop the clinical attacks, patients can become very disabled very quickly. These medications have a significant impact in reducing the likelihood of having a clinical relapse. If you can stop the relapses, you certainly can eventually stop most – if not all – of the disability accrual.”

Dr. Pittock spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and answered follow-up questions in an interview.
 

Treatment advances for NMOSD

NMOSD, also known as NMO, is a relapsing autoimmune inflammatory disorder that causes recurrent optic neuritis and myelitis. It’s a rare disease, affecting 0.5-10 people per 100,000, mostly women.

Several recent trials have supported the use of the drugs eculizumab (Soliris), satralizumab (Enspryng) and inebilizumab (Uplizna) in NMOSD, Dr. Pittock said, and all have received Food and Drug Administration approval to treat the condition over the past 2 years. Dr. Pittock led the PREVENT trial of eculizumab, which showed a 94% reduction of relapse risk versus placebo.

The newly approved drugs are stunningly expensive. According to Dr. Pittock, eculizumab costs $710,000 a year, while inebilizumab runs $393,000 the first year, then $262,000 a year. Satralizumab is $219,000 the first year, then $190,000 a year. Assistance programs are available, Dr. Pittock said, “and we’ve not had any major problems in terms of initiation.”

The cost of rituximab (Rituxan), which has a history of use as an off-label treatment option, is $18,000 a year and dropping, according to Dr. Pittock. There’s also new research on rituximab: In 2020, a small Japanese trial (n = 38) reported prevention of relapses compared with placebo, but Dr. Pittock cautioned that “the placebo patients seem to have a more benign course or more benign phenotypes” than the intervention group.

“There’s no doubt that rituximab works, but does it work as well as the other medications that have been through more of a robust trial process?” he asked. Keep in mind, he added, that perhaps 20%-50% of patients will relapse on rituximab.

Dr. Pittock advised colleagues to consider factors like patient schedules and compliance when choosing a drug. Satralizumab is self-administered monthly, while inebilizumab and rituximab are infused every 6 months.
 

Progress in anti-MOG disease

The trials in NMOSD should spur studies of the drugs in anti–myelin oligodendrocyte glycoprotein (MOG) disease, he said. “I think we’ll see a more rapid move toward phase 3 trials because of the experience with NMO. We will just have to wait and see which medications enter trial.”

Anti-MOG disease, also known as MOG antibody disease (MOGAD) and anti-MOG–associated encephalomyelitis, is caused by anti-MOG antibodies. Optic neuritis is very common, and transverse myelitis can occur.

The condition “actually responds to different drugs than MS and has a different immune pathophysiology,” Dr. Pittock said.

He cautioned colleagues to be aware that “the ability of the antibody to tell you whether or not the patient has the disease is less clear for MOGAD than it is for other diseases. If your patient has a low titer of MOG antibody, and their phenotype really doesn’t look like [MOGAD], you really need to interpret that with significant caution.”

He also highlighted a 2018 report that offers guidance about diagnosis and when MOG-IgC antibody tests are appropriate in CNS demyelinating disease.

Dr. Pittock reported numerous disclosures plus patents issued or pending.

While they’re extraordinarily expensive, a trio of newly approved medications is providing a variety of effective treatment options for patients with neuromyelitis optica spectrum disorder (NMOSD), a neurologist told colleagues.

“Patients have a choice of different options with different types of action. It’s good news,” said Sean J. Pittock, MD, of the Mayo Clinic in Rochester, Minn. “If you don’t stop the clinical attacks, patients can become very disabled very quickly. These medications have a significant impact in reducing the likelihood of having a clinical relapse. If you can stop the relapses, you certainly can eventually stop most – if not all – of the disability accrual.”

Dr. Pittock spoke at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis and answered follow-up questions in an interview.
 

Treatment advances for NMOSD

NMOSD, also known as NMO, is a relapsing autoimmune inflammatory disorder that causes recurrent optic neuritis and myelitis. It’s a rare disease, affecting 0.5-10 people per 100,000, mostly women.

Several recent trials have supported the use of the drugs eculizumab (Soliris), satralizumab (Enspryng) and inebilizumab (Uplizna) in NMOSD, Dr. Pittock said, and all have received Food and Drug Administration approval to treat the condition over the past 2 years. Dr. Pittock led the PREVENT trial of eculizumab, which showed a 94% reduction of relapse risk versus placebo.

The newly approved drugs are stunningly expensive. According to Dr. Pittock, eculizumab costs $710,000 a year, while inebilizumab runs $393,000 the first year, then $262,000 a year. Satralizumab is $219,000 the first year, then $190,000 a year. Assistance programs are available, Dr. Pittock said, “and we’ve not had any major problems in terms of initiation.”

The cost of rituximab (Rituxan), which has a history of use as an off-label treatment option, is $18,000 a year and dropping, according to Dr. Pittock. There’s also new research on rituximab: In 2020, a small Japanese trial (n = 38) reported prevention of relapses compared with placebo, but Dr. Pittock cautioned that “the placebo patients seem to have a more benign course or more benign phenotypes” than the intervention group.

“There’s no doubt that rituximab works, but does it work as well as the other medications that have been through more of a robust trial process?” he asked. Keep in mind, he added, that perhaps 20%-50% of patients will relapse on rituximab.

Dr. Pittock advised colleagues to consider factors like patient schedules and compliance when choosing a drug. Satralizumab is self-administered monthly, while inebilizumab and rituximab are infused every 6 months.
 

Progress in anti-MOG disease

The trials in NMOSD should spur studies of the drugs in anti–myelin oligodendrocyte glycoprotein (MOG) disease, he said. “I think we’ll see a more rapid move toward phase 3 trials because of the experience with NMO. We will just have to wait and see which medications enter trial.”

Anti-MOG disease, also known as MOG antibody disease (MOGAD) and anti-MOG–associated encephalomyelitis, is caused by anti-MOG antibodies. Optic neuritis is very common, and transverse myelitis can occur.

The condition “actually responds to different drugs than MS and has a different immune pathophysiology,” Dr. Pittock said.

He cautioned colleagues to be aware that “the ability of the antibody to tell you whether or not the patient has the disease is less clear for MOGAD than it is for other diseases. If your patient has a low titer of MOG antibody, and their phenotype really doesn’t look like [MOGAD], you really need to interpret that with significant caution.”

He also highlighted a 2018 report that offers guidance about diagnosis and when MOG-IgC antibody tests are appropriate in CNS demyelinating disease.

Dr. Pittock reported numerous disclosures plus patents issued or pending.

Each year, roughly 1 in 60 adult patients with multiple sclerosis (MS) aged 65 years and under is hospitalized with urinary or kidney infections, a new study suggests. That’s more than quadruple the rate in a control cohort. Other types of infections affected patients with MS at a higher rate too.

“The relative risk of all types of inpatient infections and most types of outpatient infections was significantly elevated among the patients with MS. While we expected there to be increased relative risk of urinary or kidney and respiratory infections, we also found higher relative risk of viral, fungal, skin, and opportunistic infections,” said study lead author Riley Bove, MD, an assistant professor at the Weill Institute for Neurosciences at the University of California, San Francisco, who presented the findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. She answered follow-up questions in an interview.

A common and treatable condition

“Bladder dysfunction may be present in over 80% of persons in MS and can be a significant source of decreased function and quality of life in addition to increased health care costs and morbidity,” neurologist Barbara Giesser, MD, of the University of California, Los Angeles, said in an interview. “It is common among persons with MS to have bladders that do not empty urine completely. This can predispose them to bladder and kidney infections. Also, some patients may try to self-manage bladder symptoms by restricting fluids, and this can predispose them to infection as well.”

Dr. Giesser, who was asked to comment on the present research, advised neurologists to bring up urinary disorders themselves instead of waiting for patients to mention them. “Patients are often embarrassed to start a discussion about genitourinary dysfunction with their neurologists but will be very appreciative of the opportunity for it to be investigated and treated,” she said. “Neurologists should make sure that this area of neurologic function is addressed in the routine management of their patients with MS because bladder dysfunction, morbidity, and complications associated with it are treatable and preventable.”

For her part, Dr. Bove recommended “early and effective identification of risk, appropriate referral to first-line interventions such as pelvic floor physical therapy and patient education, and early referral to urologists skilled in treating neurogenic bladder. Further, it is important to monitor side effects of medications to ensure there are no unrecognized immune deficits.”

She also cautioned that “common symptoms of [urinary tract infections] in people with MS include symptoms that are also prevalent in neurogenic bladder: urgency, incontinence, and frequency. It is possible that having baseline lower urinary tract symptoms could mask the recognition of a urinary infection, resulting in delayed recognition and treatment of the infections.”

EMD Serono funded the study. Dr. Bove is funded by the National MS Society’s Harry Weaver Award. She has received research support from Biogen and Roche Genentech and consulting/advisory board fees from Alexion, Biogen, EMD Serono, Roche Genentech, Sanofi Genzyme, and Novartis. Dr. Giesser reported no disclosures.

Each year, roughly 1 in 60 adult patients with multiple sclerosis (MS) aged 65 years and under is hospitalized with urinary or kidney infections, a new study suggests. That’s more than quadruple the rate in a control cohort. Other types of infections affected patients with MS at a higher rate too.

“The relative risk of all types of inpatient infections and most types of outpatient infections was significantly elevated among the patients with MS. While we expected there to be increased relative risk of urinary or kidney and respiratory infections, we also found higher relative risk of viral, fungal, skin, and opportunistic infections,” said study lead author Riley Bove, MD, an assistant professor at the Weill Institute for Neurosciences at the University of California, San Francisco, who presented the findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. She answered follow-up questions in an interview.

A common and treatable condition

“Bladder dysfunction may be present in over 80% of persons in MS and can be a significant source of decreased function and quality of life in addition to increased health care costs and morbidity,” neurologist Barbara Giesser, MD, of the University of California, Los Angeles, said in an interview. “It is common among persons with MS to have bladders that do not empty urine completely. This can predispose them to bladder and kidney infections. Also, some patients may try to self-manage bladder symptoms by restricting fluids, and this can predispose them to infection as well.”

Dr. Giesser, who was asked to comment on the present research, advised neurologists to bring up urinary disorders themselves instead of waiting for patients to mention them. “Patients are often embarrassed to start a discussion about genitourinary dysfunction with their neurologists but will be very appreciative of the opportunity for it to be investigated and treated,” she said. “Neurologists should make sure that this area of neurologic function is addressed in the routine management of their patients with MS because bladder dysfunction, morbidity, and complications associated with it are treatable and preventable.”

For her part, Dr. Bove recommended “early and effective identification of risk, appropriate referral to first-line interventions such as pelvic floor physical therapy and patient education, and early referral to urologists skilled in treating neurogenic bladder. Further, it is important to monitor side effects of medications to ensure there are no unrecognized immune deficits.”

She also cautioned that “common symptoms of [urinary tract infections] in people with MS include symptoms that are also prevalent in neurogenic bladder: urgency, incontinence, and frequency. It is possible that having baseline lower urinary tract symptoms could mask the recognition of a urinary infection, resulting in delayed recognition and treatment of the infections.”

EMD Serono funded the study. Dr. Bove is funded by the National MS Society’s Harry Weaver Award. She has received research support from Biogen and Roche Genentech and consulting/advisory board fees from Alexion, Biogen, EMD Serono, Roche Genentech, Sanofi Genzyme, and Novartis. Dr. Giesser reported no disclosures.

Each year, roughly 1 in 60 adult patients with multiple sclerosis (MS) aged 65 years and under is hospitalized with urinary or kidney infections, a new study suggests. That’s more than quadruple the rate in a control cohort. Other types of infections affected patients with MS at a higher rate too.

“The relative risk of all types of inpatient infections and most types of outpatient infections was significantly elevated among the patients with MS. While we expected there to be increased relative risk of urinary or kidney and respiratory infections, we also found higher relative risk of viral, fungal, skin, and opportunistic infections,” said study lead author Riley Bove, MD, an assistant professor at the Weill Institute for Neurosciences at the University of California, San Francisco, who presented the findings at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. She answered follow-up questions in an interview.

A common and treatable condition

“Bladder dysfunction may be present in over 80% of persons in MS and can be a significant source of decreased function and quality of life in addition to increased health care costs and morbidity,” neurologist Barbara Giesser, MD, of the University of California, Los Angeles, said in an interview. “It is common among persons with MS to have bladders that do not empty urine completely. This can predispose them to bladder and kidney infections. Also, some patients may try to self-manage bladder symptoms by restricting fluids, and this can predispose them to infection as well.”

Dr. Giesser, who was asked to comment on the present research, advised neurologists to bring up urinary disorders themselves instead of waiting for patients to mention them. “Patients are often embarrassed to start a discussion about genitourinary dysfunction with their neurologists but will be very appreciative of the opportunity for it to be investigated and treated,” she said. “Neurologists should make sure that this area of neurologic function is addressed in the routine management of their patients with MS because bladder dysfunction, morbidity, and complications associated with it are treatable and preventable.”

For her part, Dr. Bove recommended “early and effective identification of risk, appropriate referral to first-line interventions such as pelvic floor physical therapy and patient education, and early referral to urologists skilled in treating neurogenic bladder. Further, it is important to monitor side effects of medications to ensure there are no unrecognized immune deficits.”

She also cautioned that “common symptoms of [urinary tract infections] in people with MS include symptoms that are also prevalent in neurogenic bladder: urgency, incontinence, and frequency. It is possible that having baseline lower urinary tract symptoms could mask the recognition of a urinary infection, resulting in delayed recognition and treatment of the infections.”

EMD Serono funded the study. Dr. Bove is funded by the National MS Society’s Harry Weaver Award. She has received research support from Biogen and Roche Genentech and consulting/advisory board fees from Alexion, Biogen, EMD Serono, Roche Genentech, Sanofi Genzyme, and Novartis. Dr. Giesser reported no disclosures.

Like other people, patients with multiple sclerosis (MS) who become infected with COVID-19 face worse outcomes if they’re older and more disabled, a biostatistician told neurologists. With the exception of anti-CD20s, registries also suggest that disease-modifying therapies (DMTs) don’t cause higher degrees of severity.

“It’s good news since it’s important for patients to stay on these treatments,” said Amber Salter, PhD, MPH, an assistant professor at Washington University, St. Louis, in a follow-up interview following her presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Salter reported on the findings of several MS/COVID-19 registries from around the world, including the COViMS Registry, which is supported by the Consortium of MS Centers, the MS Society of Canada, and the National MS Society. It tracks patients who developed COVID-19 while also having MS, neuromyelitis optica, or MOG antibody disease.

The registry began collecting data in April 2020 and is ongoing. As of Jan. 29, 2021, 2,059 patients had been tracked; 85% of cases were confirmed by laboratory tests. Nearly all patients (97%) were from the United States, with about 21% from New York state. Nearly 76% were female, the average age was 48. About 70% were non-Hispanic White, 18% were African American; 83% had relapsing remitting MS, and 17% had progressive MS.

“We found that 11.5% of MS patients were reported being hospitalized, while 4.2% were admitted to the ICU or ventilated and 3% had died,” Dr. Salter said. Not surprisingly, the death rate was highest (21%) in patients aged 75 years or older, compared with 11% of those aged 65-74 years. Those with more severe cases – those who were nonambulatory – had a death rate of 18%, compared with 0.6% of those who were fully ambulatory and 4% of those who walked with assistance.

“A lot of the risks [for COVID-19 severity] we see in the general population are risks in the MS population,” Dr. Salter said.

Dr. Salter also summarized the results of other international registries. After adjustment, a registry in Italy linked the anti-CD20 drugs ocrelizumab or rituximab (odds ratio, 2.37, P = .015) and recent use of methylprednisolone (OR, 5.2; P = .001) to more severe courses of COVID-19, compared with other DMTs. And a global data-sharing project linked anti-CD20s to more severe outcomes, compared with other DMTs (hospitalization, adjusted prevalence ratio, 1.49; ICU admission, aPR, 2.55; and ventilation, aPR, 3.05).

In an interview, neurologist Lauren Gluck, MD, of Albert Einstein College of Medicine and Montefiore Medical Center, both in New York, cautioned that prescribing anti-CD20s now “requires a more complex informed consent process with patients and outlining of risk as well as strategies to minimize contracting the infection.”

Moving forward, she advised colleagues to “keep treating MS with DMTs. Preventing MS attacks will help keep patients out of the hospital and limit need for high-dose steroids.” And she cautioned that “avoiding action due to inaccurate fear of DMTs and COVID-19 may put your patients at unnecessary risk of relapses and accumulated disability. Educate your patients on the reality of the COVID19 pandemic, their personal risk of exposure, and strategies to minimize their risk.”

Fortunately, vaccinations offer protection against COVID-19 in patients with MS, although patients are clearly concerned about potential risks. “A frequent concern is whether the vaccines are safe for MS patients in general and if they could incite MS relapses,” neurologist Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, said in an interview. “The American Academy of Neurology guidelines have not found a connection between vaccination and MS relapses. Having COVID-19 infection can trigger MS relapses, so clearly the benefit from the vaccine outweighs any potential risks. Obviously, it is not advisable to take any vaccine during an active relapse, but vaccines are safe otherwise when given during remission.”

Dr. Salter and Dr. Gluck reported no relevant disclosures. Dr. Abboud reports consulting fees from Biogen, Genentech, Bristol-Myers Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myers Squibb, Genentech, and Sanofi-Genzyme.


 

Like other people, patients with multiple sclerosis (MS) who become infected with COVID-19 face worse outcomes if they’re older and more disabled, a biostatistician told neurologists. With the exception of anti-CD20s, registries also suggest that disease-modifying therapies (DMTs) don’t cause higher degrees of severity.

“It’s good news since it’s important for patients to stay on these treatments,” said Amber Salter, PhD, MPH, an assistant professor at Washington University, St. Louis, in a follow-up interview following her presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Salter reported on the findings of several MS/COVID-19 registries from around the world, including the COViMS Registry, which is supported by the Consortium of MS Centers, the MS Society of Canada, and the National MS Society. It tracks patients who developed COVID-19 while also having MS, neuromyelitis optica, or MOG antibody disease.

The registry began collecting data in April 2020 and is ongoing. As of Jan. 29, 2021, 2,059 patients had been tracked; 85% of cases were confirmed by laboratory tests. Nearly all patients (97%) were from the United States, with about 21% from New York state. Nearly 76% were female, the average age was 48. About 70% were non-Hispanic White, 18% were African American; 83% had relapsing remitting MS, and 17% had progressive MS.

“We found that 11.5% of MS patients were reported being hospitalized, while 4.2% were admitted to the ICU or ventilated and 3% had died,” Dr. Salter said. Not surprisingly, the death rate was highest (21%) in patients aged 75 years or older, compared with 11% of those aged 65-74 years. Those with more severe cases – those who were nonambulatory – had a death rate of 18%, compared with 0.6% of those who were fully ambulatory and 4% of those who walked with assistance.

“A lot of the risks [for COVID-19 severity] we see in the general population are risks in the MS population,” Dr. Salter said.

Dr. Salter also summarized the results of other international registries. After adjustment, a registry in Italy linked the anti-CD20 drugs ocrelizumab or rituximab (odds ratio, 2.37, P = .015) and recent use of methylprednisolone (OR, 5.2; P = .001) to more severe courses of COVID-19, compared with other DMTs. And a global data-sharing project linked anti-CD20s to more severe outcomes, compared with other DMTs (hospitalization, adjusted prevalence ratio, 1.49; ICU admission, aPR, 2.55; and ventilation, aPR, 3.05).

In an interview, neurologist Lauren Gluck, MD, of Albert Einstein College of Medicine and Montefiore Medical Center, both in New York, cautioned that prescribing anti-CD20s now “requires a more complex informed consent process with patients and outlining of risk as well as strategies to minimize contracting the infection.”

Moving forward, she advised colleagues to “keep treating MS with DMTs. Preventing MS attacks will help keep patients out of the hospital and limit need for high-dose steroids.” And she cautioned that “avoiding action due to inaccurate fear of DMTs and COVID-19 may put your patients at unnecessary risk of relapses and accumulated disability. Educate your patients on the reality of the COVID19 pandemic, their personal risk of exposure, and strategies to minimize their risk.”

Fortunately, vaccinations offer protection against COVID-19 in patients with MS, although patients are clearly concerned about potential risks. “A frequent concern is whether the vaccines are safe for MS patients in general and if they could incite MS relapses,” neurologist Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, said in an interview. “The American Academy of Neurology guidelines have not found a connection between vaccination and MS relapses. Having COVID-19 infection can trigger MS relapses, so clearly the benefit from the vaccine outweighs any potential risks. Obviously, it is not advisable to take any vaccine during an active relapse, but vaccines are safe otherwise when given during remission.”

Dr. Salter and Dr. Gluck reported no relevant disclosures. Dr. Abboud reports consulting fees from Biogen, Genentech, Bristol-Myers Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myers Squibb, Genentech, and Sanofi-Genzyme.


 

Like other people, patients with multiple sclerosis (MS) who become infected with COVID-19 face worse outcomes if they’re older and more disabled, a biostatistician told neurologists. With the exception of anti-CD20s, registries also suggest that disease-modifying therapies (DMTs) don’t cause higher degrees of severity.

“It’s good news since it’s important for patients to stay on these treatments,” said Amber Salter, PhD, MPH, an assistant professor at Washington University, St. Louis, in a follow-up interview following her presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Salter reported on the findings of several MS/COVID-19 registries from around the world, including the COViMS Registry, which is supported by the Consortium of MS Centers, the MS Society of Canada, and the National MS Society. It tracks patients who developed COVID-19 while also having MS, neuromyelitis optica, or MOG antibody disease.

The registry began collecting data in April 2020 and is ongoing. As of Jan. 29, 2021, 2,059 patients had been tracked; 85% of cases were confirmed by laboratory tests. Nearly all patients (97%) were from the United States, with about 21% from New York state. Nearly 76% were female, the average age was 48. About 70% were non-Hispanic White, 18% were African American; 83% had relapsing remitting MS, and 17% had progressive MS.

“We found that 11.5% of MS patients were reported being hospitalized, while 4.2% were admitted to the ICU or ventilated and 3% had died,” Dr. Salter said. Not surprisingly, the death rate was highest (21%) in patients aged 75 years or older, compared with 11% of those aged 65-74 years. Those with more severe cases – those who were nonambulatory – had a death rate of 18%, compared with 0.6% of those who were fully ambulatory and 4% of those who walked with assistance.

“A lot of the risks [for COVID-19 severity] we see in the general population are risks in the MS population,” Dr. Salter said.

Dr. Salter also summarized the results of other international registries. After adjustment, a registry in Italy linked the anti-CD20 drugs ocrelizumab or rituximab (odds ratio, 2.37, P = .015) and recent use of methylprednisolone (OR, 5.2; P = .001) to more severe courses of COVID-19, compared with other DMTs. And a global data-sharing project linked anti-CD20s to more severe outcomes, compared with other DMTs (hospitalization, adjusted prevalence ratio, 1.49; ICU admission, aPR, 2.55; and ventilation, aPR, 3.05).

In an interview, neurologist Lauren Gluck, MD, of Albert Einstein College of Medicine and Montefiore Medical Center, both in New York, cautioned that prescribing anti-CD20s now “requires a more complex informed consent process with patients and outlining of risk as well as strategies to minimize contracting the infection.”

Moving forward, she advised colleagues to “keep treating MS with DMTs. Preventing MS attacks will help keep patients out of the hospital and limit need for high-dose steroids.” And she cautioned that “avoiding action due to inaccurate fear of DMTs and COVID-19 may put your patients at unnecessary risk of relapses and accumulated disability. Educate your patients on the reality of the COVID19 pandemic, their personal risk of exposure, and strategies to minimize their risk.”

Fortunately, vaccinations offer protection against COVID-19 in patients with MS, although patients are clearly concerned about potential risks. “A frequent concern is whether the vaccines are safe for MS patients in general and if they could incite MS relapses,” neurologist Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, said in an interview. “The American Academy of Neurology guidelines have not found a connection between vaccination and MS relapses. Having COVID-19 infection can trigger MS relapses, so clearly the benefit from the vaccine outweighs any potential risks. Obviously, it is not advisable to take any vaccine during an active relapse, but vaccines are safe otherwise when given during remission.”

Dr. Salter and Dr. Gluck reported no relevant disclosures. Dr. Abboud reports consulting fees from Biogen, Genentech, Bristol-Myers Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myers Squibb, Genentech, and Sanofi-Genzyme.


 

COVID-19 vaccines are considered safe for patients with multiple sclerosis (MS), a neurologist told colleagues, but those who are on disease-modifying therapy (DMT) – or about to begin it – should be cautious about the timing of their shots.

“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.

“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”

Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”

In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”

Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”

Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.

Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).

Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.

He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”

Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”

Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
 

COVID-19 vaccines are considered safe for patients with multiple sclerosis (MS), a neurologist told colleagues, but those who are on disease-modifying therapy (DMT) – or about to begin it – should be cautious about the timing of their shots.

“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.

“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”

Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”

In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”

Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”

Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.

Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).

Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.

He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”

Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”

Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
 

COVID-19 vaccines are considered safe for patients with multiple sclerosis (MS), a neurologist told colleagues, but those who are on disease-modifying therapy (DMT) – or about to begin it – should be cautious about the timing of their shots.

“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.

“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”

Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”

In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”

Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”

Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.

Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).

Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.

He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”

Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”

Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
 

Reactions to the infusion of natalizumab (Tysabri) for the treatment of multiple sclerosis (MS) are very uncommon, are usually mild, and nearly always occur during, not after, the infusion, new studies show.

Collectively, the results suggest the need to rethink the drug’s mandatory 1-hour postinfusion observation period – particularly when unnecessarily spending time in medical settings is discouraged because of concerns regarding COVID-19, the researchers concluded.

Their findings “highlight a potential opportunity to improve and streamline the infusion and postinfusion monitoring process,” reported the authors of one of the studies. The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Infusion reactions were rare

“In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions,” they said.

The 1-hour postinfusion observation period for natalizumab, approved for the treatment of relapsing remitting MS (RRMS), is mandated by the Food and Drug Administration, as well as the European Medicines Agency, and applies to each dose, regardless of treatment duration, owing to concerns of infusion reactions. However, previous evidence has indicated that reactions are rare and are usually mild.

In addition to adding burden to the treatment regimen for patients and providers alike, any extended time in an environment where there is concern of heightened risk for SARS-CoV-2 exposure is a concern.

To evaluate the frequency, severity, and timing of infusion reactions, Yujie Wang, MD, of the department of neurology at the University of Washington, Seattle, and colleagues reviewed medical records of all patients who received natalizumab at the University of Washington MS Center’s infusion suite between July 2012 and September 2020.

Among 333 patients with RRMS, 9,682 infusions of natalizumab were provided over the study period, with a mean of 27 infusions per patient (range, 1-174). The mean age of the patients was 41 years, and 87 (26%) were male.

Overall, 33 infusion-related adverse events were reported in 26 patients, representing 0.34% of total infusions and 7.8% of patients.

In 77% of cases, the adverse event occurred during the infusion. In 92% of cases, the adverse event occurred within the first 6 months of treatment.

All of the events were described as mild. The most common were itching, gastrointestinal problems, headache, and flushing.

None of the reactions required emergency care or hospitalization. Symptoms were either self-managed or were managed easily with standard care. The treatment was continued in all cases.

“For physicians and providers who care for patients with MS and are comfortable with infusible therapies, it is no surprise that rates of clinically significant infusion reactions were low,” Dr. Wang said. “It is indeed consistent with prior studies that reactions generally occur during rather than post infusion.”

The authors underscored the array of potential benefits in making changes to the requirement. “Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients’ treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.”
 

Additional studies show consistent findings

Several other recent studies have shown similar results. In a study published in Multiple Sclerosis in October 2020, researchers with the Amsterdam University Medical Center found that, among 14,174 natalizumab infusions provided to 225 patients with RRMS between 2006 and 2018, 276 infusion-related adverse events occurred (1.95%) among 60 patients.

There were 11 severe infusion-related adverse events in nine patients (4.0%). All documented severe reactions occurred during the infusion. Among 19 moderate adverse events, 17 occurred during the infusion.

The researchers noted that the majority of patients who experienced severe infusion reactions had detectable antibodies against natalizumab. Such antibodies are associated with a higher risk for infusion-related adverse events.

Patients who did not have any symptoms of a reaction during the infusion had no clinically relevant moderate or severe reactions.

“Thus, the need for postinfusion observation will depend on the patients’ clinical status during the infusion,” they wrote. “Consequently, our data suggest that patients who do not have an infusion-related adverse event while receiving natalizumab treatment do not need to stay in the hospital for an additional observation hour.”
 

Rapid infusion protocol

In another recent study published in Multiple Sclerosis and Related Disorders in January 2021, researchers in Australia reported on the use of a rapid infusion protocol of natalizumab and ocrelizumab. The protocol was implemented to reduce the amount of time patients are required to spend in clinical settings during the COVID-19 pandemic.

In their analysis of 269 rapid infusions of natalizumab and 100 rapid infusions of ocrelizumab, there were two infusion-related reactions in the natalizumab group and eight in the ocrelizumab group.

All the reactions were mild to moderate, and no discontinuations were required. None of the reactions occurred during the postinfusion observation period.

“In the setting of COVID-19 pandemic, rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis,” the authors wrote.

Under the rapid infusion protocol, patients receive three standard doses for 1 hour followed by 30 minutes of observation. In addition, infusions are reduced to 30 minutes, explained lead author Louise Rath, of clinical neurosciences, Alfred Health, in Melbourne.

“For our cohort of patients, the side effects were minimal,” she said.

“Rapid infusions allowed patients to have option of hospital in-home or office, ensuring work was not at risk by infusion,” she added. “Our governance has been very supportive, and we will be keeping rapid infusion post COVID.”

The authors have disclosed no relevant financial relationships.

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

Reactions to the infusion of natalizumab (Tysabri) for the treatment of multiple sclerosis (MS) are very uncommon, are usually mild, and nearly always occur during, not after, the infusion, new studies show.

Collectively, the results suggest the need to rethink the drug’s mandatory 1-hour postinfusion observation period – particularly when unnecessarily spending time in medical settings is discouraged because of concerns regarding COVID-19, the researchers concluded.

Their findings “highlight a potential opportunity to improve and streamline the infusion and postinfusion monitoring process,” reported the authors of one of the studies. The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Infusion reactions were rare

“In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions,” they said.

The 1-hour postinfusion observation period for natalizumab, approved for the treatment of relapsing remitting MS (RRMS), is mandated by the Food and Drug Administration, as well as the European Medicines Agency, and applies to each dose, regardless of treatment duration, owing to concerns of infusion reactions. However, previous evidence has indicated that reactions are rare and are usually mild.

In addition to adding burden to the treatment regimen for patients and providers alike, any extended time in an environment where there is concern of heightened risk for SARS-CoV-2 exposure is a concern.

To evaluate the frequency, severity, and timing of infusion reactions, Yujie Wang, MD, of the department of neurology at the University of Washington, Seattle, and colleagues reviewed medical records of all patients who received natalizumab at the University of Washington MS Center’s infusion suite between July 2012 and September 2020.

Among 333 patients with RRMS, 9,682 infusions of natalizumab were provided over the study period, with a mean of 27 infusions per patient (range, 1-174). The mean age of the patients was 41 years, and 87 (26%) were male.

Overall, 33 infusion-related adverse events were reported in 26 patients, representing 0.34% of total infusions and 7.8% of patients.

In 77% of cases, the adverse event occurred during the infusion. In 92% of cases, the adverse event occurred within the first 6 months of treatment.

All of the events were described as mild. The most common were itching, gastrointestinal problems, headache, and flushing.

None of the reactions required emergency care or hospitalization. Symptoms were either self-managed or were managed easily with standard care. The treatment was continued in all cases.

“For physicians and providers who care for patients with MS and are comfortable with infusible therapies, it is no surprise that rates of clinically significant infusion reactions were low,” Dr. Wang said. “It is indeed consistent with prior studies that reactions generally occur during rather than post infusion.”

The authors underscored the array of potential benefits in making changes to the requirement. “Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients’ treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.”
 

Additional studies show consistent findings

Several other recent studies have shown similar results. In a study published in Multiple Sclerosis in October 2020, researchers with the Amsterdam University Medical Center found that, among 14,174 natalizumab infusions provided to 225 patients with RRMS between 2006 and 2018, 276 infusion-related adverse events occurred (1.95%) among 60 patients.

There were 11 severe infusion-related adverse events in nine patients (4.0%). All documented severe reactions occurred during the infusion. Among 19 moderate adverse events, 17 occurred during the infusion.

The researchers noted that the majority of patients who experienced severe infusion reactions had detectable antibodies against natalizumab. Such antibodies are associated with a higher risk for infusion-related adverse events.

Patients who did not have any symptoms of a reaction during the infusion had no clinically relevant moderate or severe reactions.

“Thus, the need for postinfusion observation will depend on the patients’ clinical status during the infusion,” they wrote. “Consequently, our data suggest that patients who do not have an infusion-related adverse event while receiving natalizumab treatment do not need to stay in the hospital for an additional observation hour.”
 

Rapid infusion protocol

In another recent study published in Multiple Sclerosis and Related Disorders in January 2021, researchers in Australia reported on the use of a rapid infusion protocol of natalizumab and ocrelizumab. The protocol was implemented to reduce the amount of time patients are required to spend in clinical settings during the COVID-19 pandemic.

In their analysis of 269 rapid infusions of natalizumab and 100 rapid infusions of ocrelizumab, there were two infusion-related reactions in the natalizumab group and eight in the ocrelizumab group.

All the reactions were mild to moderate, and no discontinuations were required. None of the reactions occurred during the postinfusion observation period.

“In the setting of COVID-19 pandemic, rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis,” the authors wrote.

Under the rapid infusion protocol, patients receive three standard doses for 1 hour followed by 30 minutes of observation. In addition, infusions are reduced to 30 minutes, explained lead author Louise Rath, of clinical neurosciences, Alfred Health, in Melbourne.

“For our cohort of patients, the side effects were minimal,” she said.

“Rapid infusions allowed patients to have option of hospital in-home or office, ensuring work was not at risk by infusion,” she added. “Our governance has been very supportive, and we will be keeping rapid infusion post COVID.”

The authors have disclosed no relevant financial relationships.

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

Reactions to the infusion of natalizumab (Tysabri) for the treatment of multiple sclerosis (MS) are very uncommon, are usually mild, and nearly always occur during, not after, the infusion, new studies show.

Collectively, the results suggest the need to rethink the drug’s mandatory 1-hour postinfusion observation period – particularly when unnecessarily spending time in medical settings is discouraged because of concerns regarding COVID-19, the researchers concluded.

Their findings “highlight a potential opportunity to improve and streamline the infusion and postinfusion monitoring process,” reported the authors of one of the studies. The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Infusion reactions were rare

“In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions,” they said.

The 1-hour postinfusion observation period for natalizumab, approved for the treatment of relapsing remitting MS (RRMS), is mandated by the Food and Drug Administration, as well as the European Medicines Agency, and applies to each dose, regardless of treatment duration, owing to concerns of infusion reactions. However, previous evidence has indicated that reactions are rare and are usually mild.

In addition to adding burden to the treatment regimen for patients and providers alike, any extended time in an environment where there is concern of heightened risk for SARS-CoV-2 exposure is a concern.

To evaluate the frequency, severity, and timing of infusion reactions, Yujie Wang, MD, of the department of neurology at the University of Washington, Seattle, and colleagues reviewed medical records of all patients who received natalizumab at the University of Washington MS Center’s infusion suite between July 2012 and September 2020.

Among 333 patients with RRMS, 9,682 infusions of natalizumab were provided over the study period, with a mean of 27 infusions per patient (range, 1-174). The mean age of the patients was 41 years, and 87 (26%) were male.

Overall, 33 infusion-related adverse events were reported in 26 patients, representing 0.34% of total infusions and 7.8% of patients.

In 77% of cases, the adverse event occurred during the infusion. In 92% of cases, the adverse event occurred within the first 6 months of treatment.

All of the events were described as mild. The most common were itching, gastrointestinal problems, headache, and flushing.

None of the reactions required emergency care or hospitalization. Symptoms were either self-managed or were managed easily with standard care. The treatment was continued in all cases.

“For physicians and providers who care for patients with MS and are comfortable with infusible therapies, it is no surprise that rates of clinically significant infusion reactions were low,” Dr. Wang said. “It is indeed consistent with prior studies that reactions generally occur during rather than post infusion.”

The authors underscored the array of potential benefits in making changes to the requirement. “Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients’ treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.”
 

Additional studies show consistent findings

Several other recent studies have shown similar results. In a study published in Multiple Sclerosis in October 2020, researchers with the Amsterdam University Medical Center found that, among 14,174 natalizumab infusions provided to 225 patients with RRMS between 2006 and 2018, 276 infusion-related adverse events occurred (1.95%) among 60 patients.

There were 11 severe infusion-related adverse events in nine patients (4.0%). All documented severe reactions occurred during the infusion. Among 19 moderate adverse events, 17 occurred during the infusion.

The researchers noted that the majority of patients who experienced severe infusion reactions had detectable antibodies against natalizumab. Such antibodies are associated with a higher risk for infusion-related adverse events.

Patients who did not have any symptoms of a reaction during the infusion had no clinically relevant moderate or severe reactions.

“Thus, the need for postinfusion observation will depend on the patients’ clinical status during the infusion,” they wrote. “Consequently, our data suggest that patients who do not have an infusion-related adverse event while receiving natalizumab treatment do not need to stay in the hospital for an additional observation hour.”
 

Rapid infusion protocol

In another recent study published in Multiple Sclerosis and Related Disorders in January 2021, researchers in Australia reported on the use of a rapid infusion protocol of natalizumab and ocrelizumab. The protocol was implemented to reduce the amount of time patients are required to spend in clinical settings during the COVID-19 pandemic.

In their analysis of 269 rapid infusions of natalizumab and 100 rapid infusions of ocrelizumab, there were two infusion-related reactions in the natalizumab group and eight in the ocrelizumab group.

All the reactions were mild to moderate, and no discontinuations were required. None of the reactions occurred during the postinfusion observation period.

“In the setting of COVID-19 pandemic, rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis,” the authors wrote.

Under the rapid infusion protocol, patients receive three standard doses for 1 hour followed by 30 minutes of observation. In addition, infusions are reduced to 30 minutes, explained lead author Louise Rath, of clinical neurosciences, Alfred Health, in Melbourne.

“For our cohort of patients, the side effects were minimal,” she said.

“Rapid infusions allowed patients to have option of hospital in-home or office, ensuring work was not at risk by infusion,” she added. “Our governance has been very supportive, and we will be keeping rapid infusion post COVID.”

The authors have disclosed no relevant financial relationships.

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

Elevations in serum neurofilament light chain levels in people with multiple sclerosis (MS) are significantly linked to worse neurologic function, clinical disability, and lower brain volumes, according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.

“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”

The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Scrutinizing serum neurofilament light chain levels in a real-world cohort

Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.

To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.

Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).

Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.

A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).

Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.

Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m² increase in BMI).

Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).

Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”

The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.

The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”

Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.

“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
 

Applying the findings to individual patients

Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.

“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.

“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.

Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.

“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added. 
 

Future research

In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.

The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.

“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”

The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.

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

Elevations in serum neurofilament light chain levels in people with multiple sclerosis (MS) are significantly linked to worse neurologic function, clinical disability, and lower brain volumes, according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.

“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”

The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Scrutinizing serum neurofilament light chain levels in a real-world cohort

Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.

To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.

Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).

Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.

A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).

Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.

Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m² increase in BMI).

Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).

Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”

The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.

The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”

Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.

“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
 

Applying the findings to individual patients

Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.

“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.

“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.

Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.

“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added. 
 

Future research

In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.

The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.

“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”

The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.

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

Elevations in serum neurofilament light chain levels in people with multiple sclerosis (MS) are significantly linked to worse neurologic function, clinical disability, and lower brain volumes, according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.

“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”

The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Scrutinizing serum neurofilament light chain levels in a real-world cohort

Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.

To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.

Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).

Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.

A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).

Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.

Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m² increase in BMI).

Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).

Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”

The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.

The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”

Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.

“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
 

Applying the findings to individual patients

Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.

“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.

“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.

Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.

“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added. 
 

Future research

In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.

The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.

“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”

The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.

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