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Herpes zoster infection with MS treatment higher in women?
a new study of adverse event reports on a variety of DMTs suggests.
DMTs are known to be associated with a potentially increased risk of opportunistic infections, including HZV. However, data are lacking on issues such as the relative frequency of HZV and the distribution of cases among age and gender groups, said senior author Ahmed Zayed Obeidat, MD, PhD, assistant professor at the Medical College of Wisconsin, Milwaukee.
“In my practice, we noticed patients being treated with DMTs were developing shingles at much younger ages than would be typical, so we were interested in looking at the distribution of cases among people treated with DMTs,” he said.
For the study, which was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers, Dr. Obeidat, first author Nicola Carlisle, MD, also of the Medical College of Wisconsin, and their colleagues turned to data from the Food and Drug Administration’s Adverse Event Reporting System.
They analyzed reports on adverse events involving HZV and varicella among patients with MS received between January 1999 and June 2019. The reports involved a range of MS DMTs, including interferon-beta, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, or ocrelizumab. Recently approved DMTs including cladribine and siponimod were excluded because of an insufficient number of reports.
Among 3,335 reports that were identified, they found highest mean annual report rates of HZV were for natalizumab, at 115.4, and lowest for glatiramer acetate, with just 5.3 reports. The mean annual report rates for HZV among the other DMTs were ocrelizumab, 88.3; dimethyl fumarate, 73.4; fingolimod, 72.9; interferon beta, 32.9; alemtuzumab, 21.7; and teriflunomide, 13.9.
Overall, the reports of HZV were 4.5 times more common among females, ranging from 2.1 times greater with alemtuzumab to 11.4 times greater for females with interferon-beta. The highest percentages of reports involved people in their 50s, with the exceptions of fingolimod, which had the highest rate of reports among patients in their 40s, and alemtuzumab, in which the highest percentage of reports involved patients in their 30s.
Meanwhile, as many as 25.7% of cases occurred in people under the age of 40 years, while 77.6% of total reports of HZV were in age groups between 31 years and 60 years.
“These rates are different than what is expected in the shingles population, which usually involves people over 60,” Dr. Obeidat said. He noted that, while MS is known to affect more women than men, the fivefold increase in HZV well exceeds the female-male ratio in MS, which is about 2.5:1.
Dr. Obeidat speculated that one factor explaining the higher reports of younger patients could be that fewer older patients are taking DMTs. “Many of our patients with MS may not be treated with DMTs when they are older or they may be on older DMTs that don’t have as much of a risk of opportunistic infections or activation, or some older patients may not be on medications anymore, so this may be why we are seeing this,” he said.
In commenting on the study, Joshua Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, Mass., speculated that numerous factors could explain the higher rates of women developing HZV.
“One wonders, for instance, did pregnancy play a role, were some of the women on prior medications?”
The statistical difference is interesting, he said, “but it’s hard to see what the explanation could be.”
While DMTs typically can be effective in suppressing an MS flare even if a patient develops shingles, the risks of the shingles, itself, is a concern, Dr. Katz added. “Just about any infection that stimulates an inflammatory response has some risk of worsening symptoms with MS; however, the bigger risk is probably the shingles itself and getting postherpetic neuralgia,” he explained.
“Sometimes there can be independent neurological problems just from MS, and that’s probably a bigger risk than worsening the MS,” he said. Clinicians should therefore keep shingles on their radar before starting patients on DMTs, Dr. Katz added.
“For many of the medications that are immunosuppressive, you want to check patients’ baseline levels of antibodies for zoster and if they don’t have antibodies, then you do want to vaccinate them.”
He noted that the new HZV vaccine is not a live vaccine and has a high efficacy rate, “so we think we can safely administer it in most cases.
“A concern is whether some DMTs may render the vaccine less effective, and we are looking at studying that with ocrelizumab and maybe some other B-cell depleting treatments.”
Dr. Obeidat disclosed relationships with Alexion, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Genentech, Sanofi and Novartis. Dr. Katz has been a speaker for Biogen, Genetech, Sanofi, and EMD Serono.
This article first appeared on Medscape.com.
a new study of adverse event reports on a variety of DMTs suggests.
DMTs are known to be associated with a potentially increased risk of opportunistic infections, including HZV. However, data are lacking on issues such as the relative frequency of HZV and the distribution of cases among age and gender groups, said senior author Ahmed Zayed Obeidat, MD, PhD, assistant professor at the Medical College of Wisconsin, Milwaukee.
“In my practice, we noticed patients being treated with DMTs were developing shingles at much younger ages than would be typical, so we were interested in looking at the distribution of cases among people treated with DMTs,” he said.
For the study, which was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers, Dr. Obeidat, first author Nicola Carlisle, MD, also of the Medical College of Wisconsin, and their colleagues turned to data from the Food and Drug Administration’s Adverse Event Reporting System.
They analyzed reports on adverse events involving HZV and varicella among patients with MS received between January 1999 and June 2019. The reports involved a range of MS DMTs, including interferon-beta, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, or ocrelizumab. Recently approved DMTs including cladribine and siponimod were excluded because of an insufficient number of reports.
Among 3,335 reports that were identified, they found highest mean annual report rates of HZV were for natalizumab, at 115.4, and lowest for glatiramer acetate, with just 5.3 reports. The mean annual report rates for HZV among the other DMTs were ocrelizumab, 88.3; dimethyl fumarate, 73.4; fingolimod, 72.9; interferon beta, 32.9; alemtuzumab, 21.7; and teriflunomide, 13.9.
Overall, the reports of HZV were 4.5 times more common among females, ranging from 2.1 times greater with alemtuzumab to 11.4 times greater for females with interferon-beta. The highest percentages of reports involved people in their 50s, with the exceptions of fingolimod, which had the highest rate of reports among patients in their 40s, and alemtuzumab, in which the highest percentage of reports involved patients in their 30s.
Meanwhile, as many as 25.7% of cases occurred in people under the age of 40 years, while 77.6% of total reports of HZV were in age groups between 31 years and 60 years.
“These rates are different than what is expected in the shingles population, which usually involves people over 60,” Dr. Obeidat said. He noted that, while MS is known to affect more women than men, the fivefold increase in HZV well exceeds the female-male ratio in MS, which is about 2.5:1.
Dr. Obeidat speculated that one factor explaining the higher reports of younger patients could be that fewer older patients are taking DMTs. “Many of our patients with MS may not be treated with DMTs when they are older or they may be on older DMTs that don’t have as much of a risk of opportunistic infections or activation, or some older patients may not be on medications anymore, so this may be why we are seeing this,” he said.
In commenting on the study, Joshua Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, Mass., speculated that numerous factors could explain the higher rates of women developing HZV.
“One wonders, for instance, did pregnancy play a role, were some of the women on prior medications?”
The statistical difference is interesting, he said, “but it’s hard to see what the explanation could be.”
While DMTs typically can be effective in suppressing an MS flare even if a patient develops shingles, the risks of the shingles, itself, is a concern, Dr. Katz added. “Just about any infection that stimulates an inflammatory response has some risk of worsening symptoms with MS; however, the bigger risk is probably the shingles itself and getting postherpetic neuralgia,” he explained.
“Sometimes there can be independent neurological problems just from MS, and that’s probably a bigger risk than worsening the MS,” he said. Clinicians should therefore keep shingles on their radar before starting patients on DMTs, Dr. Katz added.
“For many of the medications that are immunosuppressive, you want to check patients’ baseline levels of antibodies for zoster and if they don’t have antibodies, then you do want to vaccinate them.”
He noted that the new HZV vaccine is not a live vaccine and has a high efficacy rate, “so we think we can safely administer it in most cases.
“A concern is whether some DMTs may render the vaccine less effective, and we are looking at studying that with ocrelizumab and maybe some other B-cell depleting treatments.”
Dr. Obeidat disclosed relationships with Alexion, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Genentech, Sanofi and Novartis. Dr. Katz has been a speaker for Biogen, Genetech, Sanofi, and EMD Serono.
This article first appeared on Medscape.com.
a new study of adverse event reports on a variety of DMTs suggests.
DMTs are known to be associated with a potentially increased risk of opportunistic infections, including HZV. However, data are lacking on issues such as the relative frequency of HZV and the distribution of cases among age and gender groups, said senior author Ahmed Zayed Obeidat, MD, PhD, assistant professor at the Medical College of Wisconsin, Milwaukee.
“In my practice, we noticed patients being treated with DMTs were developing shingles at much younger ages than would be typical, so we were interested in looking at the distribution of cases among people treated with DMTs,” he said.
For the study, which was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers, Dr. Obeidat, first author Nicola Carlisle, MD, also of the Medical College of Wisconsin, and their colleagues turned to data from the Food and Drug Administration’s Adverse Event Reporting System.
They analyzed reports on adverse events involving HZV and varicella among patients with MS received between January 1999 and June 2019. The reports involved a range of MS DMTs, including interferon-beta, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, or ocrelizumab. Recently approved DMTs including cladribine and siponimod were excluded because of an insufficient number of reports.
Among 3,335 reports that were identified, they found highest mean annual report rates of HZV were for natalizumab, at 115.4, and lowest for glatiramer acetate, with just 5.3 reports. The mean annual report rates for HZV among the other DMTs were ocrelizumab, 88.3; dimethyl fumarate, 73.4; fingolimod, 72.9; interferon beta, 32.9; alemtuzumab, 21.7; and teriflunomide, 13.9.
Overall, the reports of HZV were 4.5 times more common among females, ranging from 2.1 times greater with alemtuzumab to 11.4 times greater for females with interferon-beta. The highest percentages of reports involved people in their 50s, with the exceptions of fingolimod, which had the highest rate of reports among patients in their 40s, and alemtuzumab, in which the highest percentage of reports involved patients in their 30s.
Meanwhile, as many as 25.7% of cases occurred in people under the age of 40 years, while 77.6% of total reports of HZV were in age groups between 31 years and 60 years.
“These rates are different than what is expected in the shingles population, which usually involves people over 60,” Dr. Obeidat said. He noted that, while MS is known to affect more women than men, the fivefold increase in HZV well exceeds the female-male ratio in MS, which is about 2.5:1.
Dr. Obeidat speculated that one factor explaining the higher reports of younger patients could be that fewer older patients are taking DMTs. “Many of our patients with MS may not be treated with DMTs when they are older or they may be on older DMTs that don’t have as much of a risk of opportunistic infections or activation, or some older patients may not be on medications anymore, so this may be why we are seeing this,” he said.
In commenting on the study, Joshua Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, Mass., speculated that numerous factors could explain the higher rates of women developing HZV.
“One wonders, for instance, did pregnancy play a role, were some of the women on prior medications?”
The statistical difference is interesting, he said, “but it’s hard to see what the explanation could be.”
While DMTs typically can be effective in suppressing an MS flare even if a patient develops shingles, the risks of the shingles, itself, is a concern, Dr. Katz added. “Just about any infection that stimulates an inflammatory response has some risk of worsening symptoms with MS; however, the bigger risk is probably the shingles itself and getting postherpetic neuralgia,” he explained.
“Sometimes there can be independent neurological problems just from MS, and that’s probably a bigger risk than worsening the MS,” he said. Clinicians should therefore keep shingles on their radar before starting patients on DMTs, Dr. Katz added.
“For many of the medications that are immunosuppressive, you want to check patients’ baseline levels of antibodies for zoster and if they don’t have antibodies, then you do want to vaccinate them.”
He noted that the new HZV vaccine is not a live vaccine and has a high efficacy rate, “so we think we can safely administer it in most cases.
“A concern is whether some DMTs may render the vaccine less effective, and we are looking at studying that with ocrelizumab and maybe some other B-cell depleting treatments.”
Dr. Obeidat disclosed relationships with Alexion, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Genentech, Sanofi and Novartis. Dr. Katz has been a speaker for Biogen, Genetech, Sanofi, and EMD Serono.
This article first appeared on Medscape.com.
Newest oral DMTs haven’t yet made a big impact in the MS world
So far, it’s more like a ripple, according to a study of neurologists’ prescribing patterns. “The recently approved therapies will initially be niched as later-line options,” predicted Virginia R. Schobel, MSc, nephrology franchise head at Spherix Global Insights, an independent market intelligence firm in Exton, Pa.
At the virtual annual meeting of the Consortium of Multiple Sclerosis Centers, Ms. Schobel presented the results of a retrospective chart audit Spherix conducted in February 2020 of 1,006 patients with MS who were switched to a new DMT by 199 U.S. participating neurologists within the previous 3 months. About 72% of the switchers had relapsing remitting MS (RRMS).
Assessing the three new oral DMTs
The purpose of the study was to gain an understanding of the early adoption patterns for the three recently approved oral DMTs: siponimod (Mayzent), cladribine (Mavenclad), and diroximel fumarate (Vumerity).
The first surprise was that only 41% of medication switches to a new DMT among the RRMS group were to oral DMTs; that’s a substantially lower proportion than in prior Spherix chart audits. Instead, the most popular switch was to ocrelizumab (Ocrevus), a monoclonal antibody.
“Things to keep in mind when we see the switch shares for the newer products are just how crowded this market has become and how much Ocrevus has really changed the market,” Ms. Schobel explained in an interview. “Ocrevus has become increasingly dominant in the RRMS segment, so that now there are six oral DMTs competing among themselves for a relatively limited pool of patients.”
Because of grandfathering by the Food and Drug Administration, most of the oral DMTs now share identical indications for clinically isolated syndrome, RRMS, and active secondary progressive MS. Ocrevus, she noted, has the same indications.
Only 1% of MS patients who switched to a different DMT in late 2019 or early 2020 moved to diroximel fumarate. Three percent switched to siponimod, and another 3% switched to cladribine. Switches to the three older, established oral DMTs were collectively five times more common, with 15% of patients moving to dimethyl fumarate (Tecfidera), 11% to fingolimod (Gilenya), and 9% to teriflunomide (Aubagio).
Ms. Schobel said that the three latest oral DMTs offer advantages over the older ones in terms of various combinations of efficacy, dosing schedule, and/or tolerability, which may make them attractive options as first-line therapy. She predicted that, over time as neurologists gain increasing familiarity with these drugs as first line, they will also gradually become more comfortable in turning to them as switch options.
First-time switches to an oral DMT among patients with RRMS were most often made in search of improved efficacy. Neurologists cited this as their main reason for 73% of switches to cladribine and 36% of switches to teriflunomide, with the other oral agents falling at various points in between. A switch to fingolimod was most often driven by a wish for a high-efficacy DMT with once-daily oral dosing. Improved tolerability figured prominently in switches to teriflunomide, and even more so in the relatively few changes to diroximel fumarate.
Drug switching in the pandemic era
Ms. Schobel said Spherix has been serially tracking neurologists’ prescribing for MS during the COVID-19 pandemic, which has clearly had an enormous dampening effect on medication switching. In mid-April, neurologists’ switching volume was down by 70%, compared with prepandemic figures. A slow recovery began in May, but by the end of the month prescription-switching volume was still down by 52%.
Of the neurologist prescriptions that are being run for switching thus far during the pandemic, 82% are being done via telemedicine. Therein hangs a tale, since neurology doesn’t readily lend itself to practice by telemedicine. Indeed, neurologists are using telemedicine to a lesser extent than physicians in the other specialties that Spherix monitors, according to Ms. Schobel. “COVID is definitely changing the MS world. Within MS, drug switching is now much more likely to involve a switch to a DMT that doesn’t impact the immune response and is not immunosuppressant, such as an injectable interferon or glatiramer acetate,” she said. “In this COVID world, safety and conservatism may end up trumping the move toward ‘time is brain’ which we’ve been talking so much about in recent years: the importance of getting patients on high-efficacy DMTs from the start in order to give them the best chance for positive outcomes.”
Ms. Schobel noted that Spherix received no industry funding to conduct these studies.
So far, it’s more like a ripple, according to a study of neurologists’ prescribing patterns. “The recently approved therapies will initially be niched as later-line options,” predicted Virginia R. Schobel, MSc, nephrology franchise head at Spherix Global Insights, an independent market intelligence firm in Exton, Pa.
At the virtual annual meeting of the Consortium of Multiple Sclerosis Centers, Ms. Schobel presented the results of a retrospective chart audit Spherix conducted in February 2020 of 1,006 patients with MS who were switched to a new DMT by 199 U.S. participating neurologists within the previous 3 months. About 72% of the switchers had relapsing remitting MS (RRMS).
Assessing the three new oral DMTs
The purpose of the study was to gain an understanding of the early adoption patterns for the three recently approved oral DMTs: siponimod (Mayzent), cladribine (Mavenclad), and diroximel fumarate (Vumerity).
The first surprise was that only 41% of medication switches to a new DMT among the RRMS group were to oral DMTs; that’s a substantially lower proportion than in prior Spherix chart audits. Instead, the most popular switch was to ocrelizumab (Ocrevus), a monoclonal antibody.
“Things to keep in mind when we see the switch shares for the newer products are just how crowded this market has become and how much Ocrevus has really changed the market,” Ms. Schobel explained in an interview. “Ocrevus has become increasingly dominant in the RRMS segment, so that now there are six oral DMTs competing among themselves for a relatively limited pool of patients.”
Because of grandfathering by the Food and Drug Administration, most of the oral DMTs now share identical indications for clinically isolated syndrome, RRMS, and active secondary progressive MS. Ocrevus, she noted, has the same indications.
Only 1% of MS patients who switched to a different DMT in late 2019 or early 2020 moved to diroximel fumarate. Three percent switched to siponimod, and another 3% switched to cladribine. Switches to the three older, established oral DMTs were collectively five times more common, with 15% of patients moving to dimethyl fumarate (Tecfidera), 11% to fingolimod (Gilenya), and 9% to teriflunomide (Aubagio).
Ms. Schobel said that the three latest oral DMTs offer advantages over the older ones in terms of various combinations of efficacy, dosing schedule, and/or tolerability, which may make them attractive options as first-line therapy. She predicted that, over time as neurologists gain increasing familiarity with these drugs as first line, they will also gradually become more comfortable in turning to them as switch options.
First-time switches to an oral DMT among patients with RRMS were most often made in search of improved efficacy. Neurologists cited this as their main reason for 73% of switches to cladribine and 36% of switches to teriflunomide, with the other oral agents falling at various points in between. A switch to fingolimod was most often driven by a wish for a high-efficacy DMT with once-daily oral dosing. Improved tolerability figured prominently in switches to teriflunomide, and even more so in the relatively few changes to diroximel fumarate.
Drug switching in the pandemic era
Ms. Schobel said Spherix has been serially tracking neurologists’ prescribing for MS during the COVID-19 pandemic, which has clearly had an enormous dampening effect on medication switching. In mid-April, neurologists’ switching volume was down by 70%, compared with prepandemic figures. A slow recovery began in May, but by the end of the month prescription-switching volume was still down by 52%.
Of the neurologist prescriptions that are being run for switching thus far during the pandemic, 82% are being done via telemedicine. Therein hangs a tale, since neurology doesn’t readily lend itself to practice by telemedicine. Indeed, neurologists are using telemedicine to a lesser extent than physicians in the other specialties that Spherix monitors, according to Ms. Schobel. “COVID is definitely changing the MS world. Within MS, drug switching is now much more likely to involve a switch to a DMT that doesn’t impact the immune response and is not immunosuppressant, such as an injectable interferon or glatiramer acetate,” she said. “In this COVID world, safety and conservatism may end up trumping the move toward ‘time is brain’ which we’ve been talking so much about in recent years: the importance of getting patients on high-efficacy DMTs from the start in order to give them the best chance for positive outcomes.”
Ms. Schobel noted that Spherix received no industry funding to conduct these studies.
So far, it’s more like a ripple, according to a study of neurologists’ prescribing patterns. “The recently approved therapies will initially be niched as later-line options,” predicted Virginia R. Schobel, MSc, nephrology franchise head at Spherix Global Insights, an independent market intelligence firm in Exton, Pa.
At the virtual annual meeting of the Consortium of Multiple Sclerosis Centers, Ms. Schobel presented the results of a retrospective chart audit Spherix conducted in February 2020 of 1,006 patients with MS who were switched to a new DMT by 199 U.S. participating neurologists within the previous 3 months. About 72% of the switchers had relapsing remitting MS (RRMS).
Assessing the three new oral DMTs
The purpose of the study was to gain an understanding of the early adoption patterns for the three recently approved oral DMTs: siponimod (Mayzent), cladribine (Mavenclad), and diroximel fumarate (Vumerity).
The first surprise was that only 41% of medication switches to a new DMT among the RRMS group were to oral DMTs; that’s a substantially lower proportion than in prior Spherix chart audits. Instead, the most popular switch was to ocrelizumab (Ocrevus), a monoclonal antibody.
“Things to keep in mind when we see the switch shares for the newer products are just how crowded this market has become and how much Ocrevus has really changed the market,” Ms. Schobel explained in an interview. “Ocrevus has become increasingly dominant in the RRMS segment, so that now there are six oral DMTs competing among themselves for a relatively limited pool of patients.”
Because of grandfathering by the Food and Drug Administration, most of the oral DMTs now share identical indications for clinically isolated syndrome, RRMS, and active secondary progressive MS. Ocrevus, she noted, has the same indications.
Only 1% of MS patients who switched to a different DMT in late 2019 or early 2020 moved to diroximel fumarate. Three percent switched to siponimod, and another 3% switched to cladribine. Switches to the three older, established oral DMTs were collectively five times more common, with 15% of patients moving to dimethyl fumarate (Tecfidera), 11% to fingolimod (Gilenya), and 9% to teriflunomide (Aubagio).
Ms. Schobel said that the three latest oral DMTs offer advantages over the older ones in terms of various combinations of efficacy, dosing schedule, and/or tolerability, which may make them attractive options as first-line therapy. She predicted that, over time as neurologists gain increasing familiarity with these drugs as first line, they will also gradually become more comfortable in turning to them as switch options.
First-time switches to an oral DMT among patients with RRMS were most often made in search of improved efficacy. Neurologists cited this as their main reason for 73% of switches to cladribine and 36% of switches to teriflunomide, with the other oral agents falling at various points in between. A switch to fingolimod was most often driven by a wish for a high-efficacy DMT with once-daily oral dosing. Improved tolerability figured prominently in switches to teriflunomide, and even more so in the relatively few changes to diroximel fumarate.
Drug switching in the pandemic era
Ms. Schobel said Spherix has been serially tracking neurologists’ prescribing for MS during the COVID-19 pandemic, which has clearly had an enormous dampening effect on medication switching. In mid-April, neurologists’ switching volume was down by 70%, compared with prepandemic figures. A slow recovery began in May, but by the end of the month prescription-switching volume was still down by 52%.
Of the neurologist prescriptions that are being run for switching thus far during the pandemic, 82% are being done via telemedicine. Therein hangs a tale, since neurology doesn’t readily lend itself to practice by telemedicine. Indeed, neurologists are using telemedicine to a lesser extent than physicians in the other specialties that Spherix monitors, according to Ms. Schobel. “COVID is definitely changing the MS world. Within MS, drug switching is now much more likely to involve a switch to a DMT that doesn’t impact the immune response and is not immunosuppressant, such as an injectable interferon or glatiramer acetate,” she said. “In this COVID world, safety and conservatism may end up trumping the move toward ‘time is brain’ which we’ve been talking so much about in recent years: the importance of getting patients on high-efficacy DMTs from the start in order to give them the best chance for positive outcomes.”
Ms. Schobel noted that Spherix received no industry funding to conduct these studies.
FROM CMSC 2020
Constraint-induced movement therapy may boost neuroplasticity in MS
, compared with alternative interventions with medicines. “The findings suggest for the first time that physical behavioral change therapy can significantly stimulate cortical neuroplasticity in a degenerative central nervous system disorder,” said the authors of research presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
CIMT, an intervention involving 3.5 hours/day of therapist-supervised treatment over 10 consecutive weekdays, has been shown to significantly improve paretic limb use for patients with progressive MS, and the effects are long lasting.
For patients with asymmetric upper limb nonuse, the treatment “is highly successful for promoting increased use by the more-affected arm for everyday activities,” said lead author Victor W. Mark, MD, an associate professor and medical director of the Constraint-Induced Movement Therapy Research Programs at the University of Alabama at Birmingham. “The improvements after CIMT can be found to remain as much as 1 year after the completion of the treatment, and even later. That by itself is novel for MS,” he said.
The team’s previous research in Neurorehabilitation and Neural Repair showed that the CIMT intervention is associated with statistically significant changes in white matter integrity in the brain. In this new study, Dr. Mark and colleagues sought to determine whether the effects would also translate to improvements in cortical gray matter.
Promoting neuroplasticity, improving motor function
For their study, they enrolled 20 adults with chronic MS who were matched with respect to unilateral arm disability. The participants were randomly assigned to receive 35 hours of either CIMT or a holistic complementary alternative medicine program, which included yoga, aquatic therapy, massage, and/or relaxation techniques, over the course of 2 weeks.
Both groups expressed the same degree of expectancy of benefits from the intervention. Those who received CIMT showed a significantly larger effect size on the Motor Activity Log, a measure that has been validated against real-world upper-limb accelerometry, compared with the control group (d = 3.2, vs. d = 0.7).
Imaging with tensor-based morphometry showed an increase in the thickness of the primary motor cortex in patients who underwent CIMT but not those who received the alternative medicine treatment. Furthermore, a change in the primary motor cortex was observed in the CIMT group on voxel-based morphometry, suggesting an increase in cortical density or volume, or both. Similar changes were not seen in the alternative medicine group.
“We evaluated the density of the brain cortical gray area before and after treatment, and we found increased gray matter in the area of the brain that is concentrated with voluntary limb movement (the motor cortex),” Dr. Mark said. “As in (previous) studies, we did not find such changes, or any changes, after the other form of treatment,” he said.
The results are important, Dr. Mark noted, “because CIMT seems to specifically promote neuroplasticity changes that appear to be healthy, for what is otherwise a chronically progressive degenerative neurological disorder.”
In addition to the improvements in MS, CIMT has led to improvement in motor function for patients who have experienced other central nervous system injuries, including stroke, traumatic brain injury, cerebral palsy, and, in musicians, focal hand dystonia.
The new findings offer intriguing insights into the effects in progressive MS, commented rehabilitation specialist Patricia Bobryk, MHS, a physical therapist with the UCHealth Yampa Valley Medical Center, in Colorado Springs.
“There is more evidence for CIMT in the area of stroke, which is more acute onset and with more potential recovery, especially early on, so this is exciting initial work in terms of MS,” she said.
“If we’re trying to find new avenues in the brain for better pathways, rather than using something that’s damaged in MS, it makes perfect sense that CIMT really forces and drives those connections, because you’re doing a repetitive, high-intensity patterning throughout the day, so you set up that environment for things to progress, especially in motor functioning,” she said.
Repetition, ‘prevention of compensation’
CIMT was developed at the University of Alabama, Birmingham, 30 years ago and involves four components. The first, described as “massed practice,” involves intensive, repetitive arm movements of the affected arm. The second component involves “shaping,” in which the patient is encouraged to perform his or her best attempts at the movements.
For the third component, described as “prevention of compensation,” the patient’s more-functional arm is inhibited from being used in everyday activities by wearing a padded mitt.
“This permits the patient to brace him- or herself whenever needed, but the better hand nonetheless lacks the dexterity to take over the activities that should be performed by the worse arm,” Dr. Mark explained.
“The patient wears the padded mitt after hours, too, except when using water or when sleeping,” he said.
The fourth component is a set of behavioral enforcement techniques involving goal-setting; daily interviews and discussion of progress and challenges; nightly homework; diary keeping; and telephone follow-up.
Dr. Mark noted that the intervention could have benefits that are secondary to motor and movement function. “We consider that the improvement of limb activity in a motor-challenged person with MS could afford a way to offset the deleterious effects of inactivity that can occur, such as weight gain, diabetes, osteoporosis, cardiac disease, and other conditions associated with prolonged inactivity,” he said.
Although it was developed at the University of Alabama, CIMT is currently more widely practiced in Europe than the United States, likely because of differences in care support, which in Europe is provided through socialized medicine, Dr. Mark pointed out.
Although the detailed methods for conducting CIMT are published in peer-reviewed journals, Dr. Mark recommends hands-on and interactive teaching. Such training is offered to clinicians and affiliated physical therapists and occupational therapists through Mark’s program at the University of Alabama in a semiannual, week-long training course, which includes hands-on treatment practice with actual patients.
Proof of principle
In further commenting on the study, Kathy M. Zackowski, PhD, of the National MS Society, said the findings provide an intriguing proof of concept that should be tested in a larger cohort. “The question of how much a behavioral (therapy) can impact true brain structural change or change in the pathologic mechanism is intriguing and of high importance,” she said.
“It is important to take this information as ‘proof of principle’ of the importance of CIMT for improving upper limb activity,” according to Dr. Zackowski, senior director, patient management, care and rehabilitation research at the society.
“Importantly, this team needs to move forward testing their hypothesis in a larger randomized, clinical trial with a full control group in order to show causal evidence that one intervention caused the structural brain changes seen,” she said in an interview.
Dr. Zackowski added that a caveat of CIMT is that the approach assumes one limb is more impaired than the other, which is always the case in stroke but is true only in some cases of MS. “Therefore, this method may not be effective for everyone with MS, but offers another option for tailoring an intervention to a person’s abilities and interests,” she said.
“Another important detail is that CIMT is also being explored for lower extremity use,” she added. “This is exciting, as lower extremity dysfunction is a very common problem in MS, and may be useful in treating walking disability.”
The authors, Ms. Bobryk, and Dr. Zackowski have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, compared with alternative interventions with medicines. “The findings suggest for the first time that physical behavioral change therapy can significantly stimulate cortical neuroplasticity in a degenerative central nervous system disorder,” said the authors of research presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
CIMT, an intervention involving 3.5 hours/day of therapist-supervised treatment over 10 consecutive weekdays, has been shown to significantly improve paretic limb use for patients with progressive MS, and the effects are long lasting.
For patients with asymmetric upper limb nonuse, the treatment “is highly successful for promoting increased use by the more-affected arm for everyday activities,” said lead author Victor W. Mark, MD, an associate professor and medical director of the Constraint-Induced Movement Therapy Research Programs at the University of Alabama at Birmingham. “The improvements after CIMT can be found to remain as much as 1 year after the completion of the treatment, and even later. That by itself is novel for MS,” he said.
The team’s previous research in Neurorehabilitation and Neural Repair showed that the CIMT intervention is associated with statistically significant changes in white matter integrity in the brain. In this new study, Dr. Mark and colleagues sought to determine whether the effects would also translate to improvements in cortical gray matter.
Promoting neuroplasticity, improving motor function
For their study, they enrolled 20 adults with chronic MS who were matched with respect to unilateral arm disability. The participants were randomly assigned to receive 35 hours of either CIMT or a holistic complementary alternative medicine program, which included yoga, aquatic therapy, massage, and/or relaxation techniques, over the course of 2 weeks.
Both groups expressed the same degree of expectancy of benefits from the intervention. Those who received CIMT showed a significantly larger effect size on the Motor Activity Log, a measure that has been validated against real-world upper-limb accelerometry, compared with the control group (d = 3.2, vs. d = 0.7).
Imaging with tensor-based morphometry showed an increase in the thickness of the primary motor cortex in patients who underwent CIMT but not those who received the alternative medicine treatment. Furthermore, a change in the primary motor cortex was observed in the CIMT group on voxel-based morphometry, suggesting an increase in cortical density or volume, or both. Similar changes were not seen in the alternative medicine group.
“We evaluated the density of the brain cortical gray area before and after treatment, and we found increased gray matter in the area of the brain that is concentrated with voluntary limb movement (the motor cortex),” Dr. Mark said. “As in (previous) studies, we did not find such changes, or any changes, after the other form of treatment,” he said.
The results are important, Dr. Mark noted, “because CIMT seems to specifically promote neuroplasticity changes that appear to be healthy, for what is otherwise a chronically progressive degenerative neurological disorder.”
In addition to the improvements in MS, CIMT has led to improvement in motor function for patients who have experienced other central nervous system injuries, including stroke, traumatic brain injury, cerebral palsy, and, in musicians, focal hand dystonia.
The new findings offer intriguing insights into the effects in progressive MS, commented rehabilitation specialist Patricia Bobryk, MHS, a physical therapist with the UCHealth Yampa Valley Medical Center, in Colorado Springs.
“There is more evidence for CIMT in the area of stroke, which is more acute onset and with more potential recovery, especially early on, so this is exciting initial work in terms of MS,” she said.
“If we’re trying to find new avenues in the brain for better pathways, rather than using something that’s damaged in MS, it makes perfect sense that CIMT really forces and drives those connections, because you’re doing a repetitive, high-intensity patterning throughout the day, so you set up that environment for things to progress, especially in motor functioning,” she said.
Repetition, ‘prevention of compensation’
CIMT was developed at the University of Alabama, Birmingham, 30 years ago and involves four components. The first, described as “massed practice,” involves intensive, repetitive arm movements of the affected arm. The second component involves “shaping,” in which the patient is encouraged to perform his or her best attempts at the movements.
For the third component, described as “prevention of compensation,” the patient’s more-functional arm is inhibited from being used in everyday activities by wearing a padded mitt.
“This permits the patient to brace him- or herself whenever needed, but the better hand nonetheless lacks the dexterity to take over the activities that should be performed by the worse arm,” Dr. Mark explained.
“The patient wears the padded mitt after hours, too, except when using water or when sleeping,” he said.
The fourth component is a set of behavioral enforcement techniques involving goal-setting; daily interviews and discussion of progress and challenges; nightly homework; diary keeping; and telephone follow-up.
Dr. Mark noted that the intervention could have benefits that are secondary to motor and movement function. “We consider that the improvement of limb activity in a motor-challenged person with MS could afford a way to offset the deleterious effects of inactivity that can occur, such as weight gain, diabetes, osteoporosis, cardiac disease, and other conditions associated with prolonged inactivity,” he said.
Although it was developed at the University of Alabama, CIMT is currently more widely practiced in Europe than the United States, likely because of differences in care support, which in Europe is provided through socialized medicine, Dr. Mark pointed out.
Although the detailed methods for conducting CIMT are published in peer-reviewed journals, Dr. Mark recommends hands-on and interactive teaching. Such training is offered to clinicians and affiliated physical therapists and occupational therapists through Mark’s program at the University of Alabama in a semiannual, week-long training course, which includes hands-on treatment practice with actual patients.
Proof of principle
In further commenting on the study, Kathy M. Zackowski, PhD, of the National MS Society, said the findings provide an intriguing proof of concept that should be tested in a larger cohort. “The question of how much a behavioral (therapy) can impact true brain structural change or change in the pathologic mechanism is intriguing and of high importance,” she said.
“It is important to take this information as ‘proof of principle’ of the importance of CIMT for improving upper limb activity,” according to Dr. Zackowski, senior director, patient management, care and rehabilitation research at the society.
“Importantly, this team needs to move forward testing their hypothesis in a larger randomized, clinical trial with a full control group in order to show causal evidence that one intervention caused the structural brain changes seen,” she said in an interview.
Dr. Zackowski added that a caveat of CIMT is that the approach assumes one limb is more impaired than the other, which is always the case in stroke but is true only in some cases of MS. “Therefore, this method may not be effective for everyone with MS, but offers another option for tailoring an intervention to a person’s abilities and interests,” she said.
“Another important detail is that CIMT is also being explored for lower extremity use,” she added. “This is exciting, as lower extremity dysfunction is a very common problem in MS, and may be useful in treating walking disability.”
The authors, Ms. Bobryk, and Dr. Zackowski have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, compared with alternative interventions with medicines. “The findings suggest for the first time that physical behavioral change therapy can significantly stimulate cortical neuroplasticity in a degenerative central nervous system disorder,” said the authors of research presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
CIMT, an intervention involving 3.5 hours/day of therapist-supervised treatment over 10 consecutive weekdays, has been shown to significantly improve paretic limb use for patients with progressive MS, and the effects are long lasting.
For patients with asymmetric upper limb nonuse, the treatment “is highly successful for promoting increased use by the more-affected arm for everyday activities,” said lead author Victor W. Mark, MD, an associate professor and medical director of the Constraint-Induced Movement Therapy Research Programs at the University of Alabama at Birmingham. “The improvements after CIMT can be found to remain as much as 1 year after the completion of the treatment, and even later. That by itself is novel for MS,” he said.
The team’s previous research in Neurorehabilitation and Neural Repair showed that the CIMT intervention is associated with statistically significant changes in white matter integrity in the brain. In this new study, Dr. Mark and colleagues sought to determine whether the effects would also translate to improvements in cortical gray matter.
Promoting neuroplasticity, improving motor function
For their study, they enrolled 20 adults with chronic MS who were matched with respect to unilateral arm disability. The participants were randomly assigned to receive 35 hours of either CIMT or a holistic complementary alternative medicine program, which included yoga, aquatic therapy, massage, and/or relaxation techniques, over the course of 2 weeks.
Both groups expressed the same degree of expectancy of benefits from the intervention. Those who received CIMT showed a significantly larger effect size on the Motor Activity Log, a measure that has been validated against real-world upper-limb accelerometry, compared with the control group (d = 3.2, vs. d = 0.7).
Imaging with tensor-based morphometry showed an increase in the thickness of the primary motor cortex in patients who underwent CIMT but not those who received the alternative medicine treatment. Furthermore, a change in the primary motor cortex was observed in the CIMT group on voxel-based morphometry, suggesting an increase in cortical density or volume, or both. Similar changes were not seen in the alternative medicine group.
“We evaluated the density of the brain cortical gray area before and after treatment, and we found increased gray matter in the area of the brain that is concentrated with voluntary limb movement (the motor cortex),” Dr. Mark said. “As in (previous) studies, we did not find such changes, or any changes, after the other form of treatment,” he said.
The results are important, Dr. Mark noted, “because CIMT seems to specifically promote neuroplasticity changes that appear to be healthy, for what is otherwise a chronically progressive degenerative neurological disorder.”
In addition to the improvements in MS, CIMT has led to improvement in motor function for patients who have experienced other central nervous system injuries, including stroke, traumatic brain injury, cerebral palsy, and, in musicians, focal hand dystonia.
The new findings offer intriguing insights into the effects in progressive MS, commented rehabilitation specialist Patricia Bobryk, MHS, a physical therapist with the UCHealth Yampa Valley Medical Center, in Colorado Springs.
“There is more evidence for CIMT in the area of stroke, which is more acute onset and with more potential recovery, especially early on, so this is exciting initial work in terms of MS,” she said.
“If we’re trying to find new avenues in the brain for better pathways, rather than using something that’s damaged in MS, it makes perfect sense that CIMT really forces and drives those connections, because you’re doing a repetitive, high-intensity patterning throughout the day, so you set up that environment for things to progress, especially in motor functioning,” she said.
Repetition, ‘prevention of compensation’
CIMT was developed at the University of Alabama, Birmingham, 30 years ago and involves four components. The first, described as “massed practice,” involves intensive, repetitive arm movements of the affected arm. The second component involves “shaping,” in which the patient is encouraged to perform his or her best attempts at the movements.
For the third component, described as “prevention of compensation,” the patient’s more-functional arm is inhibited from being used in everyday activities by wearing a padded mitt.
“This permits the patient to brace him- or herself whenever needed, but the better hand nonetheless lacks the dexterity to take over the activities that should be performed by the worse arm,” Dr. Mark explained.
“The patient wears the padded mitt after hours, too, except when using water or when sleeping,” he said.
The fourth component is a set of behavioral enforcement techniques involving goal-setting; daily interviews and discussion of progress and challenges; nightly homework; diary keeping; and telephone follow-up.
Dr. Mark noted that the intervention could have benefits that are secondary to motor and movement function. “We consider that the improvement of limb activity in a motor-challenged person with MS could afford a way to offset the deleterious effects of inactivity that can occur, such as weight gain, diabetes, osteoporosis, cardiac disease, and other conditions associated with prolonged inactivity,” he said.
Although it was developed at the University of Alabama, CIMT is currently more widely practiced in Europe than the United States, likely because of differences in care support, which in Europe is provided through socialized medicine, Dr. Mark pointed out.
Although the detailed methods for conducting CIMT are published in peer-reviewed journals, Dr. Mark recommends hands-on and interactive teaching. Such training is offered to clinicians and affiliated physical therapists and occupational therapists through Mark’s program at the University of Alabama in a semiannual, week-long training course, which includes hands-on treatment practice with actual patients.
Proof of principle
In further commenting on the study, Kathy M. Zackowski, PhD, of the National MS Society, said the findings provide an intriguing proof of concept that should be tested in a larger cohort. “The question of how much a behavioral (therapy) can impact true brain structural change or change in the pathologic mechanism is intriguing and of high importance,” she said.
“It is important to take this information as ‘proof of principle’ of the importance of CIMT for improving upper limb activity,” according to Dr. Zackowski, senior director, patient management, care and rehabilitation research at the society.
“Importantly, this team needs to move forward testing their hypothesis in a larger randomized, clinical trial with a full control group in order to show causal evidence that one intervention caused the structural brain changes seen,” she said in an interview.
Dr. Zackowski added that a caveat of CIMT is that the approach assumes one limb is more impaired than the other, which is always the case in stroke but is true only in some cases of MS. “Therefore, this method may not be effective for everyone with MS, but offers another option for tailoring an intervention to a person’s abilities and interests,” she said.
“Another important detail is that CIMT is also being explored for lower extremity use,” she added. “This is exciting, as lower extremity dysfunction is a very common problem in MS, and may be useful in treating walking disability.”
The authors, Ms. Bobryk, and Dr. Zackowski have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM CMSC 2020
Telerehabilitation may be effective in MS
Telerehabilitation also saves time and travel cost, compared with outpatient rehabilitation.
“This model of home-based telerehabilitation offers a safe and cost-effective method for improving function and quality of life for MS patients with mobility deficits,” said Heather Barksdale, DPT, a neurological clinical specialist at UF Health Jacksonville (Florida).
The study was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
The Centers for Medicare & Medicaid Services do not reimburse for telerehabilitation services. Patients with MS have difficulty accessing rehabilitation specialists because of impaired mobility and lack of access to transportation. “We are based in Jacksonville, Fla., and often have patients who have to travel from Tallahassee, Panama City, Daytona Beach, and Brunswick, Ga., to receive specialty services,” said Dr. Barksdale. “Telerehabilitation would allow these patients to get access to high-quality rehab services with clinicians that specialize in MS.”
Dr. Barksdale and colleagues conducted a pilot study to evaluate the feasibility of a physical therapy–guided telerehabilitation program for people with mobility impairments resulting from confirmed MS. The investigators enrolled patients at the MS Center of Excellence at University of Florida Health Jacksonville into a telerehabilitation group. A board-certified neurologist and a physical therapist specializing in MS examined participants in person at baseline. The latter underwent an 8-week program of physical therapy–guided telerehabilitation that used the Jintronix software platform and a kinetic tracking system.
By reviewing charts during January 2018–September 2019, Dr. Barksdale and colleagues selected patients with MS who were seen on an outpatient basis by the same physical therapists who were administering telerehabilitation. This outpatient comparison group was matched to the telerehabilitation group on duration of treatment and outcome measures completed. Dr. Barksdale and colleagues reviewed the data for the effects of the two interventions on mobility and travel.
Eight patients completed the telerehabilitation program, and all had improvements in fatigue, quality of life, or mobility measures. The investigators did not observe any adverse events during or after the intervention. The total savings in projected travel costs for all eight participants was $8,487.23, compared with the outpatient group. Participants in the telerehabilitation and outpatient groups achieved minimal detectable changes in the outcome measures examined at equivalent rates.
“The game-based model with virtual visits by a physical therapist can be modified to include exercises specific for other motor, coordination, spasticity, and movement dysfunctions and may be useful for other chronic and progressive dysfunction seen in Parkinson’s disease, stroke, and other movement and neuromuscular disorders,” said Dr. Barksdale.
“Future studies are needed to further establish guidelines for patient selection and mode of delivery, as well as design of future telerehabilitation programs,” she added. “Duration of treatment and types of exercises to be included should also be examined. Further research into use of telerehabilitation for the treatment of upper-extremity, cognitive, speech, and swallowing dysfunction should also be examined.”
The investigators conducted their study without outside funding and reported no disclosures.
SOURCE: Barksdale H et al. CMSC 2020. Abstract REH11.
Telerehabilitation also saves time and travel cost, compared with outpatient rehabilitation.
“This model of home-based telerehabilitation offers a safe and cost-effective method for improving function and quality of life for MS patients with mobility deficits,” said Heather Barksdale, DPT, a neurological clinical specialist at UF Health Jacksonville (Florida).
The study was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
The Centers for Medicare & Medicaid Services do not reimburse for telerehabilitation services. Patients with MS have difficulty accessing rehabilitation specialists because of impaired mobility and lack of access to transportation. “We are based in Jacksonville, Fla., and often have patients who have to travel from Tallahassee, Panama City, Daytona Beach, and Brunswick, Ga., to receive specialty services,” said Dr. Barksdale. “Telerehabilitation would allow these patients to get access to high-quality rehab services with clinicians that specialize in MS.”
Dr. Barksdale and colleagues conducted a pilot study to evaluate the feasibility of a physical therapy–guided telerehabilitation program for people with mobility impairments resulting from confirmed MS. The investigators enrolled patients at the MS Center of Excellence at University of Florida Health Jacksonville into a telerehabilitation group. A board-certified neurologist and a physical therapist specializing in MS examined participants in person at baseline. The latter underwent an 8-week program of physical therapy–guided telerehabilitation that used the Jintronix software platform and a kinetic tracking system.
By reviewing charts during January 2018–September 2019, Dr. Barksdale and colleagues selected patients with MS who were seen on an outpatient basis by the same physical therapists who were administering telerehabilitation. This outpatient comparison group was matched to the telerehabilitation group on duration of treatment and outcome measures completed. Dr. Barksdale and colleagues reviewed the data for the effects of the two interventions on mobility and travel.
Eight patients completed the telerehabilitation program, and all had improvements in fatigue, quality of life, or mobility measures. The investigators did not observe any adverse events during or after the intervention. The total savings in projected travel costs for all eight participants was $8,487.23, compared with the outpatient group. Participants in the telerehabilitation and outpatient groups achieved minimal detectable changes in the outcome measures examined at equivalent rates.
“The game-based model with virtual visits by a physical therapist can be modified to include exercises specific for other motor, coordination, spasticity, and movement dysfunctions and may be useful for other chronic and progressive dysfunction seen in Parkinson’s disease, stroke, and other movement and neuromuscular disorders,” said Dr. Barksdale.
“Future studies are needed to further establish guidelines for patient selection and mode of delivery, as well as design of future telerehabilitation programs,” she added. “Duration of treatment and types of exercises to be included should also be examined. Further research into use of telerehabilitation for the treatment of upper-extremity, cognitive, speech, and swallowing dysfunction should also be examined.”
The investigators conducted their study without outside funding and reported no disclosures.
SOURCE: Barksdale H et al. CMSC 2020. Abstract REH11.
Telerehabilitation also saves time and travel cost, compared with outpatient rehabilitation.
“This model of home-based telerehabilitation offers a safe and cost-effective method for improving function and quality of life for MS patients with mobility deficits,” said Heather Barksdale, DPT, a neurological clinical specialist at UF Health Jacksonville (Florida).
The study was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
The Centers for Medicare & Medicaid Services do not reimburse for telerehabilitation services. Patients with MS have difficulty accessing rehabilitation specialists because of impaired mobility and lack of access to transportation. “We are based in Jacksonville, Fla., and often have patients who have to travel from Tallahassee, Panama City, Daytona Beach, and Brunswick, Ga., to receive specialty services,” said Dr. Barksdale. “Telerehabilitation would allow these patients to get access to high-quality rehab services with clinicians that specialize in MS.”
Dr. Barksdale and colleagues conducted a pilot study to evaluate the feasibility of a physical therapy–guided telerehabilitation program for people with mobility impairments resulting from confirmed MS. The investigators enrolled patients at the MS Center of Excellence at University of Florida Health Jacksonville into a telerehabilitation group. A board-certified neurologist and a physical therapist specializing in MS examined participants in person at baseline. The latter underwent an 8-week program of physical therapy–guided telerehabilitation that used the Jintronix software platform and a kinetic tracking system.
By reviewing charts during January 2018–September 2019, Dr. Barksdale and colleagues selected patients with MS who were seen on an outpatient basis by the same physical therapists who were administering telerehabilitation. This outpatient comparison group was matched to the telerehabilitation group on duration of treatment and outcome measures completed. Dr. Barksdale and colleagues reviewed the data for the effects of the two interventions on mobility and travel.
Eight patients completed the telerehabilitation program, and all had improvements in fatigue, quality of life, or mobility measures. The investigators did not observe any adverse events during or after the intervention. The total savings in projected travel costs for all eight participants was $8,487.23, compared with the outpatient group. Participants in the telerehabilitation and outpatient groups achieved minimal detectable changes in the outcome measures examined at equivalent rates.
“The game-based model with virtual visits by a physical therapist can be modified to include exercises specific for other motor, coordination, spasticity, and movement dysfunctions and may be useful for other chronic and progressive dysfunction seen in Parkinson’s disease, stroke, and other movement and neuromuscular disorders,” said Dr. Barksdale.
“Future studies are needed to further establish guidelines for patient selection and mode of delivery, as well as design of future telerehabilitation programs,” she added. “Duration of treatment and types of exercises to be included should also be examined. Further research into use of telerehabilitation for the treatment of upper-extremity, cognitive, speech, and swallowing dysfunction should also be examined.”
The investigators conducted their study without outside funding and reported no disclosures.
SOURCE: Barksdale H et al. CMSC 2020. Abstract REH11.
REPORTING FROM CMSC 2020
No benefit of three commonly used medications for MS fatigue
The TRIUMPHANT study found no difference between the effects of amantadine, modafinil, methylphenidate, and placebo in the Modified Fatigue Impact Scale (MFIS) in a study involving 141 patients with MS.
There was also no difference between any of the drugs and placebo in any of the preplanned subgroups which included different Expanded Disability Status Scale scores, depressive scores, use of disease-modifying therapy, or type of MS (relapsing remitting or progressive).
The research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
“These three drugs are used very commonly used for MS fatigue by neurologists, psychiatrists, and primary care doctors, but they don’t seem to be any better than placebo. They were all associated with increased side effects compared with placebo even with short-term use,” said lead investigator Bardia Nourbakhsh, MD, assistant professor of neurology at Johns Hopkins University, Baltimore.
However, in a post hoc analysis there was an improvement in daytime sleepiness with two of the drugs – methylphenidate and modafinil. “These two agents reduced daytime sleepiness in patients with high daytime sleepiness scores at baseline, with about a 4-point difference versus placebo, which was significant. But as this was not a preplanned analysis, we have to be cautious in its interpretation,” Dr. Nourbakhsh said. “However, this finding may not be too surprising as both these drugs are licensed as stimulants for use in narcolepsy patients with excessive daytime sleepiness.”
“Our recommendations are that as amantadine was not better than placebo in any subgroup its use should be discouraged in MS fatigue,” Dr. Nourbakhsh commented. “Modafinil and methylphenidate may possibly be considered for MS patients with excessive daytime sleepiness, but this should really be confirmed in further studies.”
Fatigue is a common and debilitating symptom of MS, occurring in about 70%-80% of patients with MS. There is no approved drug treatment. However nonpharmacologic therapies have shown some success: studies of exercise and cognitive-behavioral therapy (CBT) have shown these may be effective without causing side effects, Dr. Nourbakhsh noted. “So we should be getting patients to try exercise and CBT before jumping to medication.”
Dr. Nourbakhsh said he was disappointed with the results of the study but not terribly surprised. “We use these three medications frequently in the clinic and we have not been seeing great benefits so we wondered whether they were actually effective.”
He said that the trial was adequately powered and the question has been answered. “These are valuable results – they will hopefully encourage doctors to think twice before prescribing these medications that could be harmful and have no clear benefit,” Dr. Nourbakhsh concluded.
For the randomized, double-blind, placebo-controlled, four-sequence, four-period crossover trial, 141 patients with MS and fatigue received twice-daily oral amantadine (maximum 200 mg/day), modafinil (maximum 200 mg/day), methylphenidate (maximum 20 mg/day), or placebo, each given for up to 6 weeks with a 2-week washout between each medication.
Patients had a mean baseline MFIS score of 51.3 and were randomly assigned to one of four medication administration sequences. Data from 136 participants were available for the analysis of the primary outcome (change in MFIS score), and 111 participants completed all four medication periods.
In the intent-to-treat analysis, the least-squares means of total MFIS scores at the maximally tolerated dose were as follows: 40.7 with placebo, 41.2 with amantadine, 39.0 with modafinil, and 38.7 with methylphenidate (P = .20 for the overall medication effect; P > .05 for all pairwise comparisons). “All medications and placebo reduced the MS fatigue score by 10-12 points from baseline, so there was quite a substantial placebo effect,” Dr. Nourbakhsh noted. There was no statistically significant difference in the physical and cognitive subscales of MFIS and quality of life measures between any of the study medications and placebo. All three drugs were associated with an increase in adverse effects versus placebo.
Dr. Nourbakhsh says he is hopeful that this negative study may stimulate further research into new targets and medications for MS fatigue.
His group has recently conducted a pilot study of intravenous ketamine in MS fatigue with some encouraging results, but he stressed it needs to be tested in a larger study before it can be recommended for use in clinical practice. “While an IV medication is not ideal, the effect did seem to be quite long-lived with a difference still evident at 28 days, so it could perhaps be dosed once a month, which could be feasible,” he said.
Commenting on the TRIUMPHANT study, Jeffrey Cohen, MD, of the Cleveland Clinic, said that “fatigue is a common, often disabling, symptom of MS. It is poorly understood and probably encompasses several mechanisms. There currently is no generally effective treatment for MS-related fatigue.”
“These results are not surprising and confirm previous studies,” Dr. Cohen said. “Despite no benefit from these medicines for patients as a group, they are occasionally helpful for individual patients, so they are frequently tried empirically.
“It also is important to address any factors besides MS that may be causing or contributing to fatigue, for example, sleep disruption, medication side effects, depression, other medical conditions such as anemia or hypothyroidism,” he added.
Dr. Nourbakhsh has reported receiving personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities for Jazz Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
The TRIUMPHANT study found no difference between the effects of amantadine, modafinil, methylphenidate, and placebo in the Modified Fatigue Impact Scale (MFIS) in a study involving 141 patients with MS.
There was also no difference between any of the drugs and placebo in any of the preplanned subgroups which included different Expanded Disability Status Scale scores, depressive scores, use of disease-modifying therapy, or type of MS (relapsing remitting or progressive).
The research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
“These three drugs are used very commonly used for MS fatigue by neurologists, psychiatrists, and primary care doctors, but they don’t seem to be any better than placebo. They were all associated with increased side effects compared with placebo even with short-term use,” said lead investigator Bardia Nourbakhsh, MD, assistant professor of neurology at Johns Hopkins University, Baltimore.
However, in a post hoc analysis there was an improvement in daytime sleepiness with two of the drugs – methylphenidate and modafinil. “These two agents reduced daytime sleepiness in patients with high daytime sleepiness scores at baseline, with about a 4-point difference versus placebo, which was significant. But as this was not a preplanned analysis, we have to be cautious in its interpretation,” Dr. Nourbakhsh said. “However, this finding may not be too surprising as both these drugs are licensed as stimulants for use in narcolepsy patients with excessive daytime sleepiness.”
“Our recommendations are that as amantadine was not better than placebo in any subgroup its use should be discouraged in MS fatigue,” Dr. Nourbakhsh commented. “Modafinil and methylphenidate may possibly be considered for MS patients with excessive daytime sleepiness, but this should really be confirmed in further studies.”
Fatigue is a common and debilitating symptom of MS, occurring in about 70%-80% of patients with MS. There is no approved drug treatment. However nonpharmacologic therapies have shown some success: studies of exercise and cognitive-behavioral therapy (CBT) have shown these may be effective without causing side effects, Dr. Nourbakhsh noted. “So we should be getting patients to try exercise and CBT before jumping to medication.”
Dr. Nourbakhsh said he was disappointed with the results of the study but not terribly surprised. “We use these three medications frequently in the clinic and we have not been seeing great benefits so we wondered whether they were actually effective.”
He said that the trial was adequately powered and the question has been answered. “These are valuable results – they will hopefully encourage doctors to think twice before prescribing these medications that could be harmful and have no clear benefit,” Dr. Nourbakhsh concluded.
For the randomized, double-blind, placebo-controlled, four-sequence, four-period crossover trial, 141 patients with MS and fatigue received twice-daily oral amantadine (maximum 200 mg/day), modafinil (maximum 200 mg/day), methylphenidate (maximum 20 mg/day), or placebo, each given for up to 6 weeks with a 2-week washout between each medication.
Patients had a mean baseline MFIS score of 51.3 and were randomly assigned to one of four medication administration sequences. Data from 136 participants were available for the analysis of the primary outcome (change in MFIS score), and 111 participants completed all four medication periods.
In the intent-to-treat analysis, the least-squares means of total MFIS scores at the maximally tolerated dose were as follows: 40.7 with placebo, 41.2 with amantadine, 39.0 with modafinil, and 38.7 with methylphenidate (P = .20 for the overall medication effect; P > .05 for all pairwise comparisons). “All medications and placebo reduced the MS fatigue score by 10-12 points from baseline, so there was quite a substantial placebo effect,” Dr. Nourbakhsh noted. There was no statistically significant difference in the physical and cognitive subscales of MFIS and quality of life measures between any of the study medications and placebo. All three drugs were associated with an increase in adverse effects versus placebo.
Dr. Nourbakhsh says he is hopeful that this negative study may stimulate further research into new targets and medications for MS fatigue.
His group has recently conducted a pilot study of intravenous ketamine in MS fatigue with some encouraging results, but he stressed it needs to be tested in a larger study before it can be recommended for use in clinical practice. “While an IV medication is not ideal, the effect did seem to be quite long-lived with a difference still evident at 28 days, so it could perhaps be dosed once a month, which could be feasible,” he said.
Commenting on the TRIUMPHANT study, Jeffrey Cohen, MD, of the Cleveland Clinic, said that “fatigue is a common, often disabling, symptom of MS. It is poorly understood and probably encompasses several mechanisms. There currently is no generally effective treatment for MS-related fatigue.”
“These results are not surprising and confirm previous studies,” Dr. Cohen said. “Despite no benefit from these medicines for patients as a group, they are occasionally helpful for individual patients, so they are frequently tried empirically.
“It also is important to address any factors besides MS that may be causing or contributing to fatigue, for example, sleep disruption, medication side effects, depression, other medical conditions such as anemia or hypothyroidism,” he added.
Dr. Nourbakhsh has reported receiving personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities for Jazz Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
The TRIUMPHANT study found no difference between the effects of amantadine, modafinil, methylphenidate, and placebo in the Modified Fatigue Impact Scale (MFIS) in a study involving 141 patients with MS.
There was also no difference between any of the drugs and placebo in any of the preplanned subgroups which included different Expanded Disability Status Scale scores, depressive scores, use of disease-modifying therapy, or type of MS (relapsing remitting or progressive).
The research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
“These three drugs are used very commonly used for MS fatigue by neurologists, psychiatrists, and primary care doctors, but they don’t seem to be any better than placebo. They were all associated with increased side effects compared with placebo even with short-term use,” said lead investigator Bardia Nourbakhsh, MD, assistant professor of neurology at Johns Hopkins University, Baltimore.
However, in a post hoc analysis there was an improvement in daytime sleepiness with two of the drugs – methylphenidate and modafinil. “These two agents reduced daytime sleepiness in patients with high daytime sleepiness scores at baseline, with about a 4-point difference versus placebo, which was significant. But as this was not a preplanned analysis, we have to be cautious in its interpretation,” Dr. Nourbakhsh said. “However, this finding may not be too surprising as both these drugs are licensed as stimulants for use in narcolepsy patients with excessive daytime sleepiness.”
“Our recommendations are that as amantadine was not better than placebo in any subgroup its use should be discouraged in MS fatigue,” Dr. Nourbakhsh commented. “Modafinil and methylphenidate may possibly be considered for MS patients with excessive daytime sleepiness, but this should really be confirmed in further studies.”
Fatigue is a common and debilitating symptom of MS, occurring in about 70%-80% of patients with MS. There is no approved drug treatment. However nonpharmacologic therapies have shown some success: studies of exercise and cognitive-behavioral therapy (CBT) have shown these may be effective without causing side effects, Dr. Nourbakhsh noted. “So we should be getting patients to try exercise and CBT before jumping to medication.”
Dr. Nourbakhsh said he was disappointed with the results of the study but not terribly surprised. “We use these three medications frequently in the clinic and we have not been seeing great benefits so we wondered whether they were actually effective.”
He said that the trial was adequately powered and the question has been answered. “These are valuable results – they will hopefully encourage doctors to think twice before prescribing these medications that could be harmful and have no clear benefit,” Dr. Nourbakhsh concluded.
For the randomized, double-blind, placebo-controlled, four-sequence, four-period crossover trial, 141 patients with MS and fatigue received twice-daily oral amantadine (maximum 200 mg/day), modafinil (maximum 200 mg/day), methylphenidate (maximum 20 mg/day), or placebo, each given for up to 6 weeks with a 2-week washout between each medication.
Patients had a mean baseline MFIS score of 51.3 and were randomly assigned to one of four medication administration sequences. Data from 136 participants were available for the analysis of the primary outcome (change in MFIS score), and 111 participants completed all four medication periods.
In the intent-to-treat analysis, the least-squares means of total MFIS scores at the maximally tolerated dose were as follows: 40.7 with placebo, 41.2 with amantadine, 39.0 with modafinil, and 38.7 with methylphenidate (P = .20 for the overall medication effect; P > .05 for all pairwise comparisons). “All medications and placebo reduced the MS fatigue score by 10-12 points from baseline, so there was quite a substantial placebo effect,” Dr. Nourbakhsh noted. There was no statistically significant difference in the physical and cognitive subscales of MFIS and quality of life measures between any of the study medications and placebo. All three drugs were associated with an increase in adverse effects versus placebo.
Dr. Nourbakhsh says he is hopeful that this negative study may stimulate further research into new targets and medications for MS fatigue.
His group has recently conducted a pilot study of intravenous ketamine in MS fatigue with some encouraging results, but he stressed it needs to be tested in a larger study before it can be recommended for use in clinical practice. “While an IV medication is not ideal, the effect did seem to be quite long-lived with a difference still evident at 28 days, so it could perhaps be dosed once a month, which could be feasible,” he said.
Commenting on the TRIUMPHANT study, Jeffrey Cohen, MD, of the Cleveland Clinic, said that “fatigue is a common, often disabling, symptom of MS. It is poorly understood and probably encompasses several mechanisms. There currently is no generally effective treatment for MS-related fatigue.”
“These results are not surprising and confirm previous studies,” Dr. Cohen said. “Despite no benefit from these medicines for patients as a group, they are occasionally helpful for individual patients, so they are frequently tried empirically.
“It also is important to address any factors besides MS that may be causing or contributing to fatigue, for example, sleep disruption, medication side effects, depression, other medical conditions such as anemia or hypothyroidism,” he added.
Dr. Nourbakhsh has reported receiving personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities for Jazz Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
Ofatumumab shows high elimination of disease activity in MS
, a new study shows.
The drug, which is already approved for the treatment of chronic lymphocytic leukemia, is currently under review for relapsing MS as a once-per-month self-injected therapy that could offer a convenient alternative to DMTs that require in-office infusion.
The new findings are from a pooled analysis from the phase 3 ASCLEPIOS I/II trials of the use of ofatumumab for patients with relapsing MS. There were 927 patients in the ASCLEPIOS I trial and 955 in the ASCLEPIOS II trial. The trials were conducted in 37 countries and involved patients aged 18-55 years.
The late-breaking research was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
The studies compared patients who were treated with subcutaneous ofatumumab 20 mg with patients treated with oral teriflunomide 14 mg once daily for up to 30 months. The average duration of follow-up was 18 months.
NEDA-3, commonly used to determine treatment outcomes for patients with relapsing MS, was defined as a composite of having no worsening of disability over a 6-month period (6mCDW), no confirmed MS relapse, no new/enlarging T2 lesions, and no gadolinium-enhancing T1 lesions.
The pooled results showed that the odds of achieving NEDA-3 during the first 12 months were three times greater with ofatumumab than with teriflunomide (47.0% vs. 24.5%; odds ratio [OR], 3.36; P < .001) and were more than eight times greater from months 12 to 24 (87.8% vs. 48.2%; OR, 8.09; P < .001).
In addition, compared with patients who received teriflunomide, a higher proportion of patients who received ofatumumab were free from 6mCDW over 2 years (91.9% vs. 88.9%), as well as from relapses (82.3% vs 69.2%) and lesion activity (54.1% vs. 27.5%).
There was a significantly greater reduction in annualized relapse rate with ofatumumab compared with teriflunomide at all cumulative time intervals, including months 0 to 3 (P = .011), and at all subsequent time intervals from month 0 to 27 (P < .001).
The pooled findings further showed that ofatumumab reduced the mean number of gadolinium-enhancing T1 lesions per scan by 95.9% compared with teriflunomide (P < .001).
“Ofatumumab increased the probability of achieving NEDA-3 and demonstrated superior efficacy vs teriflunomide in patients with relapsing MS,” said the authors, led by Stephen L. Hauser, MD, of the department of neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco.
Ofatumumab superior in primary, secondary outcomes
As previously reported, subcutaneous ofatumumab also demonstrated superior efficacy over oral teriflunomide in the primary and secondary endpoints in the ASCLEPIOS I/II trials. The annualized relapse rate was reduced by 0.22 in the teriflunomide group, vs 0.11 in the ofatumumab group (50.5% relative reduction; P < .001) in the ASCLEPIOS I trial, and by 0.25 vs. 0.10 (58.5% relative reduction P < .001) in ASCLEPIOS II.
Ofatumumab also reduced the number of gadolinium-enhancing T1 lesions and new or enlarging T2 lesions compared with teriflunomide (all P < .001). It reduced the risk for disability progression by 34.4% over 3 months and by 32.5% over 6 months.
In the studies, the rate of serious infection with ofatumumab was 2.5%, compared with 1.8% with teriflunomide. Rates of malignancies were 0.5% and 0.3%, respectively.
“Ofatumumab demonstrated superior efficacy versus teriflunomide, with an acceptable safety profile, in patients with relapsing MS,” the authors reported.
Adherence rates with self-injection encouraging
An additional analysis from the two trials presented virtually in a separate abstract at the CMSC showed greater adherence to the self-administered regimen.
The analysis shows that in the ASCLEPIOS I study, 86.0% patients who were randomly assigned to receive ofatumumab and 77.7% who received teriflunomide completed the study on the assigned study drug. The proportion of patients who received ofatumumab and who discontinued treatment was 14.0%, versus 21.2% for those in the teriflunomide group. The most common reasons for discontinuation were patient/guardian decision (ofatumumab, 4.9%; teriflunomide, 8.2%), adverse event (ofatumumab, 5.2%; teriflunomide, 5.0%), and physician decision (ofatumumab, 2.2%; teriflunomide, 6.5%).
In the ASCLEPIOS II study, the rates were similar in all measures.
“In ASCLEPIOS trials, compliance with home-administered subcutaneous ofatumumab was high, and fewer patients discontinued ofatumumab as compared to teriflunomide,” the authors concluded.
Comparator drug a weak choice?
In commenting on the research, Stephen Kamin, MD, professor, vice chair, and chief of service, department of neurology, New Jersey Medical School, in Newark, noted that a limitation of the ASCLEPIOS trials is the comparison with teriflunomide.
“The comparator drug, teriflunomide, is one of the least effective DMTs, and one that some clinicians, including myself, don’t use,” he said.
Previously, when asked in an interview about the choice of teriflunomide as the comparator, Dr. Hauser noted that considerable discussion had gone into the decision. “The rationale was that we wanted to have a comparator that would be present not only against focal disease activity but also potentially against progression, and we were also able to blind the study successfully,” he said at the time.
Dr. Kamin said that ofatumumab will nevertheless likely represent a welcome addition to the tool kit of treatment options for MS. “Any new drug is helpful in adding to our choices as a general rule,” he said. “Subcutaneous injection does have increased convenience.”
It is not likely that the drug will be a game changer, he added, although the treatment’s efficacy compared with other drugs remains to be seen. “It all depends upon the relative efficacy of ofatumumab versus ocrelizumab or siponimod,” Dr. Kamin said.
“There has been another subcutaneous monoclonal for MS, daclizumab, although this was withdrawn from the market due to severe adverse effects not related to route of administration,” he added.
Dr. Hauser has relationships with Alector, Annexon, Bionure, Molecular Stethoscope, Symbiotix, and F. Hoffmann-La Roche. Dr. Kamin has received research support from Biogen, Novartis and CMSC.
A version of this article originally appeared on Medscape.com.
, a new study shows.
The drug, which is already approved for the treatment of chronic lymphocytic leukemia, is currently under review for relapsing MS as a once-per-month self-injected therapy that could offer a convenient alternative to DMTs that require in-office infusion.
The new findings are from a pooled analysis from the phase 3 ASCLEPIOS I/II trials of the use of ofatumumab for patients with relapsing MS. There were 927 patients in the ASCLEPIOS I trial and 955 in the ASCLEPIOS II trial. The trials were conducted in 37 countries and involved patients aged 18-55 years.
The late-breaking research was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
The studies compared patients who were treated with subcutaneous ofatumumab 20 mg with patients treated with oral teriflunomide 14 mg once daily for up to 30 months. The average duration of follow-up was 18 months.
NEDA-3, commonly used to determine treatment outcomes for patients with relapsing MS, was defined as a composite of having no worsening of disability over a 6-month period (6mCDW), no confirmed MS relapse, no new/enlarging T2 lesions, and no gadolinium-enhancing T1 lesions.
The pooled results showed that the odds of achieving NEDA-3 during the first 12 months were three times greater with ofatumumab than with teriflunomide (47.0% vs. 24.5%; odds ratio [OR], 3.36; P < .001) and were more than eight times greater from months 12 to 24 (87.8% vs. 48.2%; OR, 8.09; P < .001).
In addition, compared with patients who received teriflunomide, a higher proportion of patients who received ofatumumab were free from 6mCDW over 2 years (91.9% vs. 88.9%), as well as from relapses (82.3% vs 69.2%) and lesion activity (54.1% vs. 27.5%).
There was a significantly greater reduction in annualized relapse rate with ofatumumab compared with teriflunomide at all cumulative time intervals, including months 0 to 3 (P = .011), and at all subsequent time intervals from month 0 to 27 (P < .001).
The pooled findings further showed that ofatumumab reduced the mean number of gadolinium-enhancing T1 lesions per scan by 95.9% compared with teriflunomide (P < .001).
“Ofatumumab increased the probability of achieving NEDA-3 and demonstrated superior efficacy vs teriflunomide in patients with relapsing MS,” said the authors, led by Stephen L. Hauser, MD, of the department of neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco.
Ofatumumab superior in primary, secondary outcomes
As previously reported, subcutaneous ofatumumab also demonstrated superior efficacy over oral teriflunomide in the primary and secondary endpoints in the ASCLEPIOS I/II trials. The annualized relapse rate was reduced by 0.22 in the teriflunomide group, vs 0.11 in the ofatumumab group (50.5% relative reduction; P < .001) in the ASCLEPIOS I trial, and by 0.25 vs. 0.10 (58.5% relative reduction P < .001) in ASCLEPIOS II.
Ofatumumab also reduced the number of gadolinium-enhancing T1 lesions and new or enlarging T2 lesions compared with teriflunomide (all P < .001). It reduced the risk for disability progression by 34.4% over 3 months and by 32.5% over 6 months.
In the studies, the rate of serious infection with ofatumumab was 2.5%, compared with 1.8% with teriflunomide. Rates of malignancies were 0.5% and 0.3%, respectively.
“Ofatumumab demonstrated superior efficacy versus teriflunomide, with an acceptable safety profile, in patients with relapsing MS,” the authors reported.
Adherence rates with self-injection encouraging
An additional analysis from the two trials presented virtually in a separate abstract at the CMSC showed greater adherence to the self-administered regimen.
The analysis shows that in the ASCLEPIOS I study, 86.0% patients who were randomly assigned to receive ofatumumab and 77.7% who received teriflunomide completed the study on the assigned study drug. The proportion of patients who received ofatumumab and who discontinued treatment was 14.0%, versus 21.2% for those in the teriflunomide group. The most common reasons for discontinuation were patient/guardian decision (ofatumumab, 4.9%; teriflunomide, 8.2%), adverse event (ofatumumab, 5.2%; teriflunomide, 5.0%), and physician decision (ofatumumab, 2.2%; teriflunomide, 6.5%).
In the ASCLEPIOS II study, the rates were similar in all measures.
“In ASCLEPIOS trials, compliance with home-administered subcutaneous ofatumumab was high, and fewer patients discontinued ofatumumab as compared to teriflunomide,” the authors concluded.
Comparator drug a weak choice?
In commenting on the research, Stephen Kamin, MD, professor, vice chair, and chief of service, department of neurology, New Jersey Medical School, in Newark, noted that a limitation of the ASCLEPIOS trials is the comparison with teriflunomide.
“The comparator drug, teriflunomide, is one of the least effective DMTs, and one that some clinicians, including myself, don’t use,” he said.
Previously, when asked in an interview about the choice of teriflunomide as the comparator, Dr. Hauser noted that considerable discussion had gone into the decision. “The rationale was that we wanted to have a comparator that would be present not only against focal disease activity but also potentially against progression, and we were also able to blind the study successfully,” he said at the time.
Dr. Kamin said that ofatumumab will nevertheless likely represent a welcome addition to the tool kit of treatment options for MS. “Any new drug is helpful in adding to our choices as a general rule,” he said. “Subcutaneous injection does have increased convenience.”
It is not likely that the drug will be a game changer, he added, although the treatment’s efficacy compared with other drugs remains to be seen. “It all depends upon the relative efficacy of ofatumumab versus ocrelizumab or siponimod,” Dr. Kamin said.
“There has been another subcutaneous monoclonal for MS, daclizumab, although this was withdrawn from the market due to severe adverse effects not related to route of administration,” he added.
Dr. Hauser has relationships with Alector, Annexon, Bionure, Molecular Stethoscope, Symbiotix, and F. Hoffmann-La Roche. Dr. Kamin has received research support from Biogen, Novartis and CMSC.
A version of this article originally appeared on Medscape.com.
, a new study shows.
The drug, which is already approved for the treatment of chronic lymphocytic leukemia, is currently under review for relapsing MS as a once-per-month self-injected therapy that could offer a convenient alternative to DMTs that require in-office infusion.
The new findings are from a pooled analysis from the phase 3 ASCLEPIOS I/II trials of the use of ofatumumab for patients with relapsing MS. There were 927 patients in the ASCLEPIOS I trial and 955 in the ASCLEPIOS II trial. The trials were conducted in 37 countries and involved patients aged 18-55 years.
The late-breaking research was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
The studies compared patients who were treated with subcutaneous ofatumumab 20 mg with patients treated with oral teriflunomide 14 mg once daily for up to 30 months. The average duration of follow-up was 18 months.
NEDA-3, commonly used to determine treatment outcomes for patients with relapsing MS, was defined as a composite of having no worsening of disability over a 6-month period (6mCDW), no confirmed MS relapse, no new/enlarging T2 lesions, and no gadolinium-enhancing T1 lesions.
The pooled results showed that the odds of achieving NEDA-3 during the first 12 months were three times greater with ofatumumab than with teriflunomide (47.0% vs. 24.5%; odds ratio [OR], 3.36; P < .001) and were more than eight times greater from months 12 to 24 (87.8% vs. 48.2%; OR, 8.09; P < .001).
In addition, compared with patients who received teriflunomide, a higher proportion of patients who received ofatumumab were free from 6mCDW over 2 years (91.9% vs. 88.9%), as well as from relapses (82.3% vs 69.2%) and lesion activity (54.1% vs. 27.5%).
There was a significantly greater reduction in annualized relapse rate with ofatumumab compared with teriflunomide at all cumulative time intervals, including months 0 to 3 (P = .011), and at all subsequent time intervals from month 0 to 27 (P < .001).
The pooled findings further showed that ofatumumab reduced the mean number of gadolinium-enhancing T1 lesions per scan by 95.9% compared with teriflunomide (P < .001).
“Ofatumumab increased the probability of achieving NEDA-3 and demonstrated superior efficacy vs teriflunomide in patients with relapsing MS,” said the authors, led by Stephen L. Hauser, MD, of the department of neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco.
Ofatumumab superior in primary, secondary outcomes
As previously reported, subcutaneous ofatumumab also demonstrated superior efficacy over oral teriflunomide in the primary and secondary endpoints in the ASCLEPIOS I/II trials. The annualized relapse rate was reduced by 0.22 in the teriflunomide group, vs 0.11 in the ofatumumab group (50.5% relative reduction; P < .001) in the ASCLEPIOS I trial, and by 0.25 vs. 0.10 (58.5% relative reduction P < .001) in ASCLEPIOS II.
Ofatumumab also reduced the number of gadolinium-enhancing T1 lesions and new or enlarging T2 lesions compared with teriflunomide (all P < .001). It reduced the risk for disability progression by 34.4% over 3 months and by 32.5% over 6 months.
In the studies, the rate of serious infection with ofatumumab was 2.5%, compared with 1.8% with teriflunomide. Rates of malignancies were 0.5% and 0.3%, respectively.
“Ofatumumab demonstrated superior efficacy versus teriflunomide, with an acceptable safety profile, in patients with relapsing MS,” the authors reported.
Adherence rates with self-injection encouraging
An additional analysis from the two trials presented virtually in a separate abstract at the CMSC showed greater adherence to the self-administered regimen.
The analysis shows that in the ASCLEPIOS I study, 86.0% patients who were randomly assigned to receive ofatumumab and 77.7% who received teriflunomide completed the study on the assigned study drug. The proportion of patients who received ofatumumab and who discontinued treatment was 14.0%, versus 21.2% for those in the teriflunomide group. The most common reasons for discontinuation were patient/guardian decision (ofatumumab, 4.9%; teriflunomide, 8.2%), adverse event (ofatumumab, 5.2%; teriflunomide, 5.0%), and physician decision (ofatumumab, 2.2%; teriflunomide, 6.5%).
In the ASCLEPIOS II study, the rates were similar in all measures.
“In ASCLEPIOS trials, compliance with home-administered subcutaneous ofatumumab was high, and fewer patients discontinued ofatumumab as compared to teriflunomide,” the authors concluded.
Comparator drug a weak choice?
In commenting on the research, Stephen Kamin, MD, professor, vice chair, and chief of service, department of neurology, New Jersey Medical School, in Newark, noted that a limitation of the ASCLEPIOS trials is the comparison with teriflunomide.
“The comparator drug, teriflunomide, is one of the least effective DMTs, and one that some clinicians, including myself, don’t use,” he said.
Previously, when asked in an interview about the choice of teriflunomide as the comparator, Dr. Hauser noted that considerable discussion had gone into the decision. “The rationale was that we wanted to have a comparator that would be present not only against focal disease activity but also potentially against progression, and we were also able to blind the study successfully,” he said at the time.
Dr. Kamin said that ofatumumab will nevertheless likely represent a welcome addition to the tool kit of treatment options for MS. “Any new drug is helpful in adding to our choices as a general rule,” he said. “Subcutaneous injection does have increased convenience.”
It is not likely that the drug will be a game changer, he added, although the treatment’s efficacy compared with other drugs remains to be seen. “It all depends upon the relative efficacy of ofatumumab versus ocrelizumab or siponimod,” Dr. Kamin said.
“There has been another subcutaneous monoclonal for MS, daclizumab, although this was withdrawn from the market due to severe adverse effects not related to route of administration,” he added.
Dr. Hauser has relationships with Alector, Annexon, Bionure, Molecular Stethoscope, Symbiotix, and F. Hoffmann-La Roche. Dr. Kamin has received research support from Biogen, Novartis and CMSC.
A version of this article originally appeared on Medscape.com.
From CMSC 2020
Natalizumab switch to moderate-efficacy DMT increases disability risk
, new research shows.
“Owing to the vast number of available DMTs, not only understanding DMT performance but answering the question of what can come next if a patient needs to discontinue treatment due to safety or breakthrough disease is important,” said lead author Carrie M. Hersh, DO, of the Lou Ruvo Center for Brain Health, Cleveland Clinic, Las Vegas.
The study shows that, “patients transitioning from natalizumab to another high-efficacy therapy have better inflammatory and disability outcomes compared with those who de-escalate their therapy to a moderate-efficacy DMT,” she said.
Natalizumab (Tysabri) offers significant benefits in the treatment of relapsing forms of MS, however, its long-term use is associated with safety concerns, notably an increased risk of progressive multifocal leukoencephalopathy (PML). Although the risk can be reduced with a switch to a different DMT, the transition can have risks of its own, including a rebound of disease activity that could prove to be worse than the pre-natalizumab treatment period, and there is a lack of consensus on the safest avenues for switching to another DMT following discontinuation of natalizumab.
In research presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers, Dr. Hersh and colleagues explored the issue in a real-world population of 556 patients discontinuing natalizumab at two MS centers. Of these, 270 switched to a moderate DMT (dimethyl fumarate, n = 130; or fingolimod, n = 140) and 130 switched to a highly effective DMT (ocrelizumab, n = 106; rituximab, n = 17; or alemtuzumab, n = 7).
Reasons for switching included a PML risk for 54.9%, breakthrough disease for 15.3%, and adverse effects for 17.3%.
At 24-month follow-up after the switch and after adjustment for propensity score matching, no differences were seen between the moderate and highly effective DMT groups in terms of the annualized relapse rate (ARR; P = 0.33) or the time to first relapse (P = 0.09).
However, significantly higher proportions of patients switching to moderate DMTs showed new T2 lesions (odds ratio, 2.15; P = .01), as well as new gadolinium-enhancing lesions (OR, 1.99; P = .02), and a 20% worsening of the timed 25-foot walk test (T25FW; OR, 1.83; P = .04) and 9-hole peg test (9-HPT; OR, 1.81; P = .04)
Those switching to moderate DMTs also had significantly lower rates of absence of disease activity over the 24 months (OR, 0.41, P = .004), and they had a higher risk of earlier time-to-first gadolinium-enhancing lesion (hazard ratio, 6.67, P = .002), compared with those switching to a high-efficacy DMT.
Other factors that have previously been shown to be associated with rebounds that are worse than pre-natalizumab treatment include washout periods that are longer than 3 months.
The authors noted that there were no significant differences between the groups in terms of mean washout duration, which were relatively short (moderate DMT, 1.4 months; highly effective treatment, 1.8 months; P = .34), In addition, there were no significant differences between the groups in terms of the average duration of natalizumab treatment.
Dr. Hersh speculated that the lack of ARR differences may reflect that the measure is not as objective as the more specific determinants of performance. “One could consider the comparable ARR as a little surprising, but relapse evaluation in a retrospective manner is limited,” she explained.
“Historically, radiographic markers of new inflammation via brain magnetic resonance imaging (MRI) and neuroperformance measures (T25FW and 9-HPT) are more objective compared to assessing clinical relapses, especially in a retrospective cohort where relapses cannot be validated by a central agency or the principal investigator. Therefore, one can surmise that patients transitioning from natalizumab to another high-efficacy DMT fare better than de-escalating treatment to a moderate-efficacy DMT.”
Dr. Hersh and team plan a larger, multicenter study to investigate the short- and long-term effects of post-natalizumab DMT sequencing to help validate the current findings.
Commenting on the research, Stephen Kamin, MD, professor, vice chair and chief of service, department of neurology, New Jersey Medical School, Newark, said the results are consistent with natalizumab’s general profile.
“In general, natalizumab has been used in patients with highly active disease, so I would expect fewer patients with no evidence of disease activity when switched to a moderately active drug rather than a highly active one,” he said in an interview.
Caveats of the findings include the trial’s observational nature, meaning potential confounding factors of baseline characteristics among patients who switched regimens are not known, noted Dr. Kamin, who was not involved with the study.
“Also, the patients were switched to a variety of drugs and even within a class there may be differences in outcome,” he explained.
Dr. Hersh reported consulting or research relationships with Biogen, Genentech, EMD Serono, Genzyme, Novartis, and PCORI. Dr. Kamin has received research support from Biogen, Novartis, and the Consortium of Multiple Sclerosis Centers.
This article first appeared on Medscape.com.
, new research shows.
“Owing to the vast number of available DMTs, not only understanding DMT performance but answering the question of what can come next if a patient needs to discontinue treatment due to safety or breakthrough disease is important,” said lead author Carrie M. Hersh, DO, of the Lou Ruvo Center for Brain Health, Cleveland Clinic, Las Vegas.
The study shows that, “patients transitioning from natalizumab to another high-efficacy therapy have better inflammatory and disability outcomes compared with those who de-escalate their therapy to a moderate-efficacy DMT,” she said.
Natalizumab (Tysabri) offers significant benefits in the treatment of relapsing forms of MS, however, its long-term use is associated with safety concerns, notably an increased risk of progressive multifocal leukoencephalopathy (PML). Although the risk can be reduced with a switch to a different DMT, the transition can have risks of its own, including a rebound of disease activity that could prove to be worse than the pre-natalizumab treatment period, and there is a lack of consensus on the safest avenues for switching to another DMT following discontinuation of natalizumab.
In research presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers, Dr. Hersh and colleagues explored the issue in a real-world population of 556 patients discontinuing natalizumab at two MS centers. Of these, 270 switched to a moderate DMT (dimethyl fumarate, n = 130; or fingolimod, n = 140) and 130 switched to a highly effective DMT (ocrelizumab, n = 106; rituximab, n = 17; or alemtuzumab, n = 7).
Reasons for switching included a PML risk for 54.9%, breakthrough disease for 15.3%, and adverse effects for 17.3%.
At 24-month follow-up after the switch and after adjustment for propensity score matching, no differences were seen between the moderate and highly effective DMT groups in terms of the annualized relapse rate (ARR; P = 0.33) or the time to first relapse (P = 0.09).
However, significantly higher proportions of patients switching to moderate DMTs showed new T2 lesions (odds ratio, 2.15; P = .01), as well as new gadolinium-enhancing lesions (OR, 1.99; P = .02), and a 20% worsening of the timed 25-foot walk test (T25FW; OR, 1.83; P = .04) and 9-hole peg test (9-HPT; OR, 1.81; P = .04)
Those switching to moderate DMTs also had significantly lower rates of absence of disease activity over the 24 months (OR, 0.41, P = .004), and they had a higher risk of earlier time-to-first gadolinium-enhancing lesion (hazard ratio, 6.67, P = .002), compared with those switching to a high-efficacy DMT.
Other factors that have previously been shown to be associated with rebounds that are worse than pre-natalizumab treatment include washout periods that are longer than 3 months.
The authors noted that there were no significant differences between the groups in terms of mean washout duration, which were relatively short (moderate DMT, 1.4 months; highly effective treatment, 1.8 months; P = .34), In addition, there were no significant differences between the groups in terms of the average duration of natalizumab treatment.
Dr. Hersh speculated that the lack of ARR differences may reflect that the measure is not as objective as the more specific determinants of performance. “One could consider the comparable ARR as a little surprising, but relapse evaluation in a retrospective manner is limited,” she explained.
“Historically, radiographic markers of new inflammation via brain magnetic resonance imaging (MRI) and neuroperformance measures (T25FW and 9-HPT) are more objective compared to assessing clinical relapses, especially in a retrospective cohort where relapses cannot be validated by a central agency or the principal investigator. Therefore, one can surmise that patients transitioning from natalizumab to another high-efficacy DMT fare better than de-escalating treatment to a moderate-efficacy DMT.”
Dr. Hersh and team plan a larger, multicenter study to investigate the short- and long-term effects of post-natalizumab DMT sequencing to help validate the current findings.
Commenting on the research, Stephen Kamin, MD, professor, vice chair and chief of service, department of neurology, New Jersey Medical School, Newark, said the results are consistent with natalizumab’s general profile.
“In general, natalizumab has been used in patients with highly active disease, so I would expect fewer patients with no evidence of disease activity when switched to a moderately active drug rather than a highly active one,” he said in an interview.
Caveats of the findings include the trial’s observational nature, meaning potential confounding factors of baseline characteristics among patients who switched regimens are not known, noted Dr. Kamin, who was not involved with the study.
“Also, the patients were switched to a variety of drugs and even within a class there may be differences in outcome,” he explained.
Dr. Hersh reported consulting or research relationships with Biogen, Genentech, EMD Serono, Genzyme, Novartis, and PCORI. Dr. Kamin has received research support from Biogen, Novartis, and the Consortium of Multiple Sclerosis Centers.
This article first appeared on Medscape.com.
, new research shows.
“Owing to the vast number of available DMTs, not only understanding DMT performance but answering the question of what can come next if a patient needs to discontinue treatment due to safety or breakthrough disease is important,” said lead author Carrie M. Hersh, DO, of the Lou Ruvo Center for Brain Health, Cleveland Clinic, Las Vegas.
The study shows that, “patients transitioning from natalizumab to another high-efficacy therapy have better inflammatory and disability outcomes compared with those who de-escalate their therapy to a moderate-efficacy DMT,” she said.
Natalizumab (Tysabri) offers significant benefits in the treatment of relapsing forms of MS, however, its long-term use is associated with safety concerns, notably an increased risk of progressive multifocal leukoencephalopathy (PML). Although the risk can be reduced with a switch to a different DMT, the transition can have risks of its own, including a rebound of disease activity that could prove to be worse than the pre-natalizumab treatment period, and there is a lack of consensus on the safest avenues for switching to another DMT following discontinuation of natalizumab.
In research presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers, Dr. Hersh and colleagues explored the issue in a real-world population of 556 patients discontinuing natalizumab at two MS centers. Of these, 270 switched to a moderate DMT (dimethyl fumarate, n = 130; or fingolimod, n = 140) and 130 switched to a highly effective DMT (ocrelizumab, n = 106; rituximab, n = 17; or alemtuzumab, n = 7).
Reasons for switching included a PML risk for 54.9%, breakthrough disease for 15.3%, and adverse effects for 17.3%.
At 24-month follow-up after the switch and after adjustment for propensity score matching, no differences were seen between the moderate and highly effective DMT groups in terms of the annualized relapse rate (ARR; P = 0.33) or the time to first relapse (P = 0.09).
However, significantly higher proportions of patients switching to moderate DMTs showed new T2 lesions (odds ratio, 2.15; P = .01), as well as new gadolinium-enhancing lesions (OR, 1.99; P = .02), and a 20% worsening of the timed 25-foot walk test (T25FW; OR, 1.83; P = .04) and 9-hole peg test (9-HPT; OR, 1.81; P = .04)
Those switching to moderate DMTs also had significantly lower rates of absence of disease activity over the 24 months (OR, 0.41, P = .004), and they had a higher risk of earlier time-to-first gadolinium-enhancing lesion (hazard ratio, 6.67, P = .002), compared with those switching to a high-efficacy DMT.
Other factors that have previously been shown to be associated with rebounds that are worse than pre-natalizumab treatment include washout periods that are longer than 3 months.
The authors noted that there were no significant differences between the groups in terms of mean washout duration, which were relatively short (moderate DMT, 1.4 months; highly effective treatment, 1.8 months; P = .34), In addition, there were no significant differences between the groups in terms of the average duration of natalizumab treatment.
Dr. Hersh speculated that the lack of ARR differences may reflect that the measure is not as objective as the more specific determinants of performance. “One could consider the comparable ARR as a little surprising, but relapse evaluation in a retrospective manner is limited,” she explained.
“Historically, radiographic markers of new inflammation via brain magnetic resonance imaging (MRI) and neuroperformance measures (T25FW and 9-HPT) are more objective compared to assessing clinical relapses, especially in a retrospective cohort where relapses cannot be validated by a central agency or the principal investigator. Therefore, one can surmise that patients transitioning from natalizumab to another high-efficacy DMT fare better than de-escalating treatment to a moderate-efficacy DMT.”
Dr. Hersh and team plan a larger, multicenter study to investigate the short- and long-term effects of post-natalizumab DMT sequencing to help validate the current findings.
Commenting on the research, Stephen Kamin, MD, professor, vice chair and chief of service, department of neurology, New Jersey Medical School, Newark, said the results are consistent with natalizumab’s general profile.
“In general, natalizumab has been used in patients with highly active disease, so I would expect fewer patients with no evidence of disease activity when switched to a moderately active drug rather than a highly active one,” he said in an interview.
Caveats of the findings include the trial’s observational nature, meaning potential confounding factors of baseline characteristics among patients who switched regimens are not known, noted Dr. Kamin, who was not involved with the study.
“Also, the patients were switched to a variety of drugs and even within a class there may be differences in outcome,” he explained.
Dr. Hersh reported consulting or research relationships with Biogen, Genentech, EMD Serono, Genzyme, Novartis, and PCORI. Dr. Kamin has received research support from Biogen, Novartis, and the Consortium of Multiple Sclerosis Centers.
This article first appeared on Medscape.com.
High levels of air pollution linked to increased MS risk
, new research suggests. A large cohort study of almost 550,000 individuals living in Italy showed that participants living in areas with high levels of pollutants had a significantly greater risk of developing MS than those who lived in areas with low levels of pollutants.
The findings further confirm a relationship between exposure to air pollutants and risk for MS that has been shown in previous research, said Roberto Bergamaschi, MD, PhD, director of the Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy.
“Countermeasures that cut air pollution can be important for public health, not only to reduce deaths related to cardiac and pulmonary diseases but also the risk of chronic autoimmune diseases such as MS,” Dr. Bergamaschi said.
The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.
Toxic pollutants
Several environmental factors may trigger an abnormal immune response that manifests in MS. The most studied of these are low vitamin D level, cigarette smoking, and an unhealthy diet, Dr. Bergamaschi said. However, “other environmental factors deserve to be studied—pollution included,” he added.
Among the most toxic air pollutants are particulate matter (PM), which is a mixture of fine solid and liquid particles suspended in the earth’s atmosphere. PM may range from 2.5 microns (PM2.5) to 10 microns (PM10) in diameter.
The main sources of such pollutants are household and commercial heating (53%) and industrial activities (17%), followed by road vehicle and non–road vehicle use, agriculture, and electricity production.
The World Health Organization estimates that more than 3.2 million individuals worldwide die prematurely every year because of lung cancer, cardiovascular disease, and other diseases related to air pollutants, said Dr. Bergamaschi.
Epidemiologic research has uncovered a relationship between air pollution and MS. A large American study published in 2008 in Science of the Total Environment showed a significant association between MS prevalence and PM10 levels (P < 0.001). Other studies have shown an increase in the number of clinical relapses of MS that were linked to air pollution.
The current investigators assessed the association between PM2.5 levels and MS prevalence in the northern province of Pavia, which has a population of 547,251 individuals in 188 municipalities.
Peculiar features
Pavia is situated in a flat territory that encompasses the highly industrialized regions of Piedmont, Lombardy, Emilia-Romagna, and Veneto. It has a high level of anthropogenic emissions, or environmental pollutants, originating from human activity, Dr. Bergamaschi reported. The region also has “peculiar” geographical features that “favor the accumulation of pollutants,” such as the natural barrier of the Alps in the north and low wind speed, he said.
The researchers identified 927 individuals with MS (315 male and 612 female) in the province. The overall MS prevalence rate was 169.4 per 100,000 population (95% confidence interval [CI], 158.8 – 180.6), which is 10-fold higher than 50 years ago, Dr. Bergamaschi said. In addition, this MS prevalence is higher than that in the United States, which is about 150 per 100,000 population.
Using sophisticated Bayesian disease mapping, the investigators looked for clusters of MS. They also gathered emission data for PM2.5 from 2010 to 2017 from the European Monitoring and Evaluation Programme database. They then divided the region on the basis of average winter concentrations of PM2.5.
Three distinct lateral areas of air pollution were identified. The more northern region, which includes the large urban center of Milan, had the highest level of air pollution. Concentrations decreased the further south the investigators looked.
After adjusting for age, urbanization (population density), and deprivation index, results showed that living in areas with high levels of pollutants was associated with increased MS risk. When controlling for PM2.5 pollution, participants in urban areas had an increased risk for MS compared with rural dwellers (relative risk [RR], 1.16; 95% CI, 1.04 – 1.30; P = 0.003)
Dr. Bergamaschi said it is unclear whether this risk is higher for certain types of MS. “To my knowledge, no study has analyzed possible relationships between MS phenotypes and air pollution,” he noted.
Vitamin D’s role?
Several mechanisms might help explain the relationship between air pollution and MS risk, he added. These include oxidative stress, which results in cell damage, inflammation, and proinflammatory cytokine release. Vitamin D also likely plays some role, Dr. Bergamaschi said. Upon penetrating the lower strata of the earth’s atmosphere, ultraviolet B radiation is absorbed and scattered by suspended pollutants.
Several studies have highlighted the correlation between living in a polluted area and vitamin D hypovitaminosis; “so air pollution can contribute to increasing the risk of MS by reducing vitamin D synthesis,” he said.
Recent research has also shown that air pollution is associated with a higher risk for other autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes mellitus.
However, pollution alone is only part of the picture. MS prevalence in highly populated and polluted countries such as China and India is low, with no more than 30 to 40 cases per 100,000 population, Dr. Bergamaschi noted. “This discrepancy is explained by different genetic backgrounds. While Caucasians are particularly susceptible to MS, Asians are not,” he said.
Study limitations cited included a possible bias because the analysis did not include other possible contributing risk factors, particularly other pollutants, Dr. Bergamaschi said.
Commenting on the research, Lily Jung Henson, MD, chief of neurology at Piedmont Healthcare in Stockbridge, Georgia, said the findings provide “a fascinating glimpse” into possible causative factors for MS and warrant further investigation.
“This research also suggests other opportunities to look at, such as progression of the degree of air pollution and the incidence of MS over time,” said Dr. Henson, who was not involved with the study.
Drs. Bergamaschi and Dr. Henson have reported no relevant financial relationships.
This article first appeared on Medscape.com.
, new research suggests. A large cohort study of almost 550,000 individuals living in Italy showed that participants living in areas with high levels of pollutants had a significantly greater risk of developing MS than those who lived in areas with low levels of pollutants.
The findings further confirm a relationship between exposure to air pollutants and risk for MS that has been shown in previous research, said Roberto Bergamaschi, MD, PhD, director of the Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy.
“Countermeasures that cut air pollution can be important for public health, not only to reduce deaths related to cardiac and pulmonary diseases but also the risk of chronic autoimmune diseases such as MS,” Dr. Bergamaschi said.
The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.
Toxic pollutants
Several environmental factors may trigger an abnormal immune response that manifests in MS. The most studied of these are low vitamin D level, cigarette smoking, and an unhealthy diet, Dr. Bergamaschi said. However, “other environmental factors deserve to be studied—pollution included,” he added.
Among the most toxic air pollutants are particulate matter (PM), which is a mixture of fine solid and liquid particles suspended in the earth’s atmosphere. PM may range from 2.5 microns (PM2.5) to 10 microns (PM10) in diameter.
The main sources of such pollutants are household and commercial heating (53%) and industrial activities (17%), followed by road vehicle and non–road vehicle use, agriculture, and electricity production.
The World Health Organization estimates that more than 3.2 million individuals worldwide die prematurely every year because of lung cancer, cardiovascular disease, and other diseases related to air pollutants, said Dr. Bergamaschi.
Epidemiologic research has uncovered a relationship between air pollution and MS. A large American study published in 2008 in Science of the Total Environment showed a significant association between MS prevalence and PM10 levels (P < 0.001). Other studies have shown an increase in the number of clinical relapses of MS that were linked to air pollution.
The current investigators assessed the association between PM2.5 levels and MS prevalence in the northern province of Pavia, which has a population of 547,251 individuals in 188 municipalities.
Peculiar features
Pavia is situated in a flat territory that encompasses the highly industrialized regions of Piedmont, Lombardy, Emilia-Romagna, and Veneto. It has a high level of anthropogenic emissions, or environmental pollutants, originating from human activity, Dr. Bergamaschi reported. The region also has “peculiar” geographical features that “favor the accumulation of pollutants,” such as the natural barrier of the Alps in the north and low wind speed, he said.
The researchers identified 927 individuals with MS (315 male and 612 female) in the province. The overall MS prevalence rate was 169.4 per 100,000 population (95% confidence interval [CI], 158.8 – 180.6), which is 10-fold higher than 50 years ago, Dr. Bergamaschi said. In addition, this MS prevalence is higher than that in the United States, which is about 150 per 100,000 population.
Using sophisticated Bayesian disease mapping, the investigators looked for clusters of MS. They also gathered emission data for PM2.5 from 2010 to 2017 from the European Monitoring and Evaluation Programme database. They then divided the region on the basis of average winter concentrations of PM2.5.
Three distinct lateral areas of air pollution were identified. The more northern region, which includes the large urban center of Milan, had the highest level of air pollution. Concentrations decreased the further south the investigators looked.
After adjusting for age, urbanization (population density), and deprivation index, results showed that living in areas with high levels of pollutants was associated with increased MS risk. When controlling for PM2.5 pollution, participants in urban areas had an increased risk for MS compared with rural dwellers (relative risk [RR], 1.16; 95% CI, 1.04 – 1.30; P = 0.003)
Dr. Bergamaschi said it is unclear whether this risk is higher for certain types of MS. “To my knowledge, no study has analyzed possible relationships between MS phenotypes and air pollution,” he noted.
Vitamin D’s role?
Several mechanisms might help explain the relationship between air pollution and MS risk, he added. These include oxidative stress, which results in cell damage, inflammation, and proinflammatory cytokine release. Vitamin D also likely plays some role, Dr. Bergamaschi said. Upon penetrating the lower strata of the earth’s atmosphere, ultraviolet B radiation is absorbed and scattered by suspended pollutants.
Several studies have highlighted the correlation between living in a polluted area and vitamin D hypovitaminosis; “so air pollution can contribute to increasing the risk of MS by reducing vitamin D synthesis,” he said.
Recent research has also shown that air pollution is associated with a higher risk for other autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes mellitus.
However, pollution alone is only part of the picture. MS prevalence in highly populated and polluted countries such as China and India is low, with no more than 30 to 40 cases per 100,000 population, Dr. Bergamaschi noted. “This discrepancy is explained by different genetic backgrounds. While Caucasians are particularly susceptible to MS, Asians are not,” he said.
Study limitations cited included a possible bias because the analysis did not include other possible contributing risk factors, particularly other pollutants, Dr. Bergamaschi said.
Commenting on the research, Lily Jung Henson, MD, chief of neurology at Piedmont Healthcare in Stockbridge, Georgia, said the findings provide “a fascinating glimpse” into possible causative factors for MS and warrant further investigation.
“This research also suggests other opportunities to look at, such as progression of the degree of air pollution and the incidence of MS over time,” said Dr. Henson, who was not involved with the study.
Drs. Bergamaschi and Dr. Henson have reported no relevant financial relationships.
This article first appeared on Medscape.com.
, new research suggests. A large cohort study of almost 550,000 individuals living in Italy showed that participants living in areas with high levels of pollutants had a significantly greater risk of developing MS than those who lived in areas with low levels of pollutants.
The findings further confirm a relationship between exposure to air pollutants and risk for MS that has been shown in previous research, said Roberto Bergamaschi, MD, PhD, director of the Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy.
“Countermeasures that cut air pollution can be important for public health, not only to reduce deaths related to cardiac and pulmonary diseases but also the risk of chronic autoimmune diseases such as MS,” Dr. Bergamaschi said.
The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.
Toxic pollutants
Several environmental factors may trigger an abnormal immune response that manifests in MS. The most studied of these are low vitamin D level, cigarette smoking, and an unhealthy diet, Dr. Bergamaschi said. However, “other environmental factors deserve to be studied—pollution included,” he added.
Among the most toxic air pollutants are particulate matter (PM), which is a mixture of fine solid and liquid particles suspended in the earth’s atmosphere. PM may range from 2.5 microns (PM2.5) to 10 microns (PM10) in diameter.
The main sources of such pollutants are household and commercial heating (53%) and industrial activities (17%), followed by road vehicle and non–road vehicle use, agriculture, and electricity production.
The World Health Organization estimates that more than 3.2 million individuals worldwide die prematurely every year because of lung cancer, cardiovascular disease, and other diseases related to air pollutants, said Dr. Bergamaschi.
Epidemiologic research has uncovered a relationship between air pollution and MS. A large American study published in 2008 in Science of the Total Environment showed a significant association between MS prevalence and PM10 levels (P < 0.001). Other studies have shown an increase in the number of clinical relapses of MS that were linked to air pollution.
The current investigators assessed the association between PM2.5 levels and MS prevalence in the northern province of Pavia, which has a population of 547,251 individuals in 188 municipalities.
Peculiar features
Pavia is situated in a flat territory that encompasses the highly industrialized regions of Piedmont, Lombardy, Emilia-Romagna, and Veneto. It has a high level of anthropogenic emissions, or environmental pollutants, originating from human activity, Dr. Bergamaschi reported. The region also has “peculiar” geographical features that “favor the accumulation of pollutants,” such as the natural barrier of the Alps in the north and low wind speed, he said.
The researchers identified 927 individuals with MS (315 male and 612 female) in the province. The overall MS prevalence rate was 169.4 per 100,000 population (95% confidence interval [CI], 158.8 – 180.6), which is 10-fold higher than 50 years ago, Dr. Bergamaschi said. In addition, this MS prevalence is higher than that in the United States, which is about 150 per 100,000 population.
Using sophisticated Bayesian disease mapping, the investigators looked for clusters of MS. They also gathered emission data for PM2.5 from 2010 to 2017 from the European Monitoring and Evaluation Programme database. They then divided the region on the basis of average winter concentrations of PM2.5.
Three distinct lateral areas of air pollution were identified. The more northern region, which includes the large urban center of Milan, had the highest level of air pollution. Concentrations decreased the further south the investigators looked.
After adjusting for age, urbanization (population density), and deprivation index, results showed that living in areas with high levels of pollutants was associated with increased MS risk. When controlling for PM2.5 pollution, participants in urban areas had an increased risk for MS compared with rural dwellers (relative risk [RR], 1.16; 95% CI, 1.04 – 1.30; P = 0.003)
Dr. Bergamaschi said it is unclear whether this risk is higher for certain types of MS. “To my knowledge, no study has analyzed possible relationships between MS phenotypes and air pollution,” he noted.
Vitamin D’s role?
Several mechanisms might help explain the relationship between air pollution and MS risk, he added. These include oxidative stress, which results in cell damage, inflammation, and proinflammatory cytokine release. Vitamin D also likely plays some role, Dr. Bergamaschi said. Upon penetrating the lower strata of the earth’s atmosphere, ultraviolet B radiation is absorbed and scattered by suspended pollutants.
Several studies have highlighted the correlation between living in a polluted area and vitamin D hypovitaminosis; “so air pollution can contribute to increasing the risk of MS by reducing vitamin D synthesis,” he said.
Recent research has also shown that air pollution is associated with a higher risk for other autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes mellitus.
However, pollution alone is only part of the picture. MS prevalence in highly populated and polluted countries such as China and India is low, with no more than 30 to 40 cases per 100,000 population, Dr. Bergamaschi noted. “This discrepancy is explained by different genetic backgrounds. While Caucasians are particularly susceptible to MS, Asians are not,” he said.
Study limitations cited included a possible bias because the analysis did not include other possible contributing risk factors, particularly other pollutants, Dr. Bergamaschi said.
Commenting on the research, Lily Jung Henson, MD, chief of neurology at Piedmont Healthcare in Stockbridge, Georgia, said the findings provide “a fascinating glimpse” into possible causative factors for MS and warrant further investigation.
“This research also suggests other opportunities to look at, such as progression of the degree of air pollution and the incidence of MS over time,” said Dr. Henson, who was not involved with the study.
Drs. Bergamaschi and Dr. Henson have reported no relevant financial relationships.
This article first appeared on Medscape.com.
FROM EAN 2020
Progressive multiple sclerosis linked to faster retinal layer thinning
Key clinical point: Inner nuclear layer (INL) and outer nuclear layer (ONL) measures may be novel biomarkers of neurodegeneration in patients with progressive multiple sclerosis (PMS).
Major finding: Independent of age, PMS vs. relapsing-remitting MS (RRMS) was associated with a faster thinning of peri-papillary retinal nerve fiber layer (β = −0.34%/year; P less than .001), ganglion cell+inner plexiform layer (β = −0.27%/year; P less than .001), INL (β = −0.10%/year; P = .01), and ONL (β = −0.13%/year; P = .01).
Study details: In all, 178 RRMS, 186 PMS, and 66 control participants were followed for a median of 3.7 years; retinal imaging was performed with spectral-domain optical coherence tomography.
Disclosures: This study was funded by the NIH/NINDS, National MS Society, Race to Erase MS, Walters Foundation, and ACTRIMS. The authors declared no conflict of interest.
Citation: Sotirchos ES et al. Ann Neurol. 2020 Apr 13. doi: 10.1002/ana.25738.
Key clinical point: Inner nuclear layer (INL) and outer nuclear layer (ONL) measures may be novel biomarkers of neurodegeneration in patients with progressive multiple sclerosis (PMS).
Major finding: Independent of age, PMS vs. relapsing-remitting MS (RRMS) was associated with a faster thinning of peri-papillary retinal nerve fiber layer (β = −0.34%/year; P less than .001), ganglion cell+inner plexiform layer (β = −0.27%/year; P less than .001), INL (β = −0.10%/year; P = .01), and ONL (β = −0.13%/year; P = .01).
Study details: In all, 178 RRMS, 186 PMS, and 66 control participants were followed for a median of 3.7 years; retinal imaging was performed with spectral-domain optical coherence tomography.
Disclosures: This study was funded by the NIH/NINDS, National MS Society, Race to Erase MS, Walters Foundation, and ACTRIMS. The authors declared no conflict of interest.
Citation: Sotirchos ES et al. Ann Neurol. 2020 Apr 13. doi: 10.1002/ana.25738.
Key clinical point: Inner nuclear layer (INL) and outer nuclear layer (ONL) measures may be novel biomarkers of neurodegeneration in patients with progressive multiple sclerosis (PMS).
Major finding: Independent of age, PMS vs. relapsing-remitting MS (RRMS) was associated with a faster thinning of peri-papillary retinal nerve fiber layer (β = −0.34%/year; P less than .001), ganglion cell+inner plexiform layer (β = −0.27%/year; P less than .001), INL (β = −0.10%/year; P = .01), and ONL (β = −0.13%/year; P = .01).
Study details: In all, 178 RRMS, 186 PMS, and 66 control participants were followed for a median of 3.7 years; retinal imaging was performed with spectral-domain optical coherence tomography.
Disclosures: This study was funded by the NIH/NINDS, National MS Society, Race to Erase MS, Walters Foundation, and ACTRIMS. The authors declared no conflict of interest.
Citation: Sotirchos ES et al. Ann Neurol. 2020 Apr 13. doi: 10.1002/ana.25738.
Newly diagnosed MS patients more likely to have impaired cognitive function
Key clinical point: Patients with newly diagnosed multiple sclerosis (MS) or clinically isolated syndrome (CIS) are more likely to have subtly impaired cognitive function irrespective of race/ethnicity.
Major finding: Mean oral Symbol Digit Modalities Test (SDMT) scores were lower in patients with MS/CIS vs. control participants (52.2 vs. 58.3; P less than .0001). Independent predictors of lower oral SDMT scores included being black (β = −5.97) or Hispanic (β = −3.06), having MS (β = −6.04), lower educational attainment (β = −5.02), and having a household income ≤$65,000 (β = −2.28). No significant interaction was found between race/ethnicity and having MS on SDMT scores (P = .41).
Study details: 1,174 adult patients (mean age, 40.7 years) from the MS Sunshine Study were included in this analysis (MS/CIS cases, n = 554; matched control participants, n = 620).
Disclosures: This study was supported in part by the National Institute of Neurologic Disorders and Stroke. The presenting author received personal compensation or funding from Genzyme, Biogen, Serrono, MedDay, and Novartis, and grant support from the NIH, the National MS Society, California Community Foundation, and the Charitable Guthy-Jackson Foundation.
Citation: Amezcua L et al. Neurology. 2020 Mar 9. doi: 10.1212/WNL.0000000000009210.
Key clinical point: Patients with newly diagnosed multiple sclerosis (MS) or clinically isolated syndrome (CIS) are more likely to have subtly impaired cognitive function irrespective of race/ethnicity.
Major finding: Mean oral Symbol Digit Modalities Test (SDMT) scores were lower in patients with MS/CIS vs. control participants (52.2 vs. 58.3; P less than .0001). Independent predictors of lower oral SDMT scores included being black (β = −5.97) or Hispanic (β = −3.06), having MS (β = −6.04), lower educational attainment (β = −5.02), and having a household income ≤$65,000 (β = −2.28). No significant interaction was found between race/ethnicity and having MS on SDMT scores (P = .41).
Study details: 1,174 adult patients (mean age, 40.7 years) from the MS Sunshine Study were included in this analysis (MS/CIS cases, n = 554; matched control participants, n = 620).
Disclosures: This study was supported in part by the National Institute of Neurologic Disorders and Stroke. The presenting author received personal compensation or funding from Genzyme, Biogen, Serrono, MedDay, and Novartis, and grant support from the NIH, the National MS Society, California Community Foundation, and the Charitable Guthy-Jackson Foundation.
Citation: Amezcua L et al. Neurology. 2020 Mar 9. doi: 10.1212/WNL.0000000000009210.
Key clinical point: Patients with newly diagnosed multiple sclerosis (MS) or clinically isolated syndrome (CIS) are more likely to have subtly impaired cognitive function irrespective of race/ethnicity.
Major finding: Mean oral Symbol Digit Modalities Test (SDMT) scores were lower in patients with MS/CIS vs. control participants (52.2 vs. 58.3; P less than .0001). Independent predictors of lower oral SDMT scores included being black (β = −5.97) or Hispanic (β = −3.06), having MS (β = −6.04), lower educational attainment (β = −5.02), and having a household income ≤$65,000 (β = −2.28). No significant interaction was found between race/ethnicity and having MS on SDMT scores (P = .41).
Study details: 1,174 adult patients (mean age, 40.7 years) from the MS Sunshine Study were included in this analysis (MS/CIS cases, n = 554; matched control participants, n = 620).
Disclosures: This study was supported in part by the National Institute of Neurologic Disorders and Stroke. The presenting author received personal compensation or funding from Genzyme, Biogen, Serrono, MedDay, and Novartis, and grant support from the NIH, the National MS Society, California Community Foundation, and the Charitable Guthy-Jackson Foundation.
Citation: Amezcua L et al. Neurology. 2020 Mar 9. doi: 10.1212/WNL.0000000000009210.