ICYMI Multiple Sclerosis

NEW ORLEANS—Most patients with relapsing-remitting multiple sclerosis (MS) with highly active disease remain free of new MRI activity for six years after receiving alemtuzumab, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. The durable effects may result from the distinct pattern of lymphocyte repopulation following treatment with alemtuzumab, which may lead to a rebalancing of the immune system, said Anthony Traboulsee, MD, Associate Professor of Neurology at the University of British Columbia in Vancouver. Additional mechanistic studies are needed to establish this hypothesis, the authors said.

To evaluate six-year MRI and brain volume loss outcomes in a subset of patient with highly active disease at baseline who were treated with alemtuzumab, Dr. Traboulsee and colleagues analyzed data from the CARE-MS I trial. In that trial, researchers randomized patients with active relapsing-remitting MS who were drug-naïve at baseline to alemtuzumab or interferon beta-1a. After two years, patients who received alemtuzumab had improved clinical and MRI outcomes, including brain loss volume, compared with patients who received interferon beta-1a. In addition, significantly more of these patients had no evidence of disease activity, compared with patients treated with interferon beta1-a.

In an extension study, patients could receive additional treatment with alemtuzumab (12 mg/day on three consecutive days one year or more after the most recent course) as needed for relapse or radiologic activity. During the extension, patients also could receive treatment with other licensed disease-modifying therapies at an investigator’s discretion. Retreatment criteria included one or more relapse, two or more new or enlarging T2 hyperintense lesions, or new gadolinium-enhancing T1 brain or spinal cord lesions on MRI. Researchers defined highly active disease as two or more relapses a year prior to randomization and one or more gadolinium-enhancing T1 lesion at core study baseline.

The researchers obtained MRI scans at baseline and yearly thereafter. Experts masked to patients’ original treatment group assignment analyzed the MRI scans. Investigators assessed the proportion of patients free of MRI disease activity (ie, no new or enlarging T2 hyperintense lesions or new gadolinium-enhancing T1 lesions) and the proportion of patients free of new non-enhancing T1 lesions. Brain volume loss was derived by brain parenchymal fraction change.

Of 376 patients who received alemtuzumab in the CARE-MS I trial, 105 met the criteria for highly active disease at core study baseline. Of these 105 patients, 99 remained in the study through Year 6. Through six years, 63% of patients did not receive additional treatment with alemtuzumab or another disease-modifying therapy. In each year through Year 6, a majority of patients were free of MRI disease activity (61 % at Year 6), free of new gadolinium-enhancing T1 lesions (83% at Year 6), and free of new or enlarging T2 hyperintense lesions (62% at Year 6). The investigators also observed that annually in Years 2 through 6, high proportions of patients had no new non-enhancing T1 hypointense lesions.

“These findings, along with long-term clinical efficacy, suggest that alemtuzumab may provide a unique treatment approach for relapsing-remitting MS patients with highly active disease, offering durable efficacy in the absence of continuous treatment,” said Dr. Traboulsee and colleagues.

NEW ORLEANS—Most patients with relapsing-remitting multiple sclerosis (MS) with highly active disease remain free of new MRI activity for six years after receiving alemtuzumab, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. The durable effects may result from the distinct pattern of lymphocyte repopulation following treatment with alemtuzumab, which may lead to a rebalancing of the immune system, said Anthony Traboulsee, MD, Associate Professor of Neurology at the University of British Columbia in Vancouver. Additional mechanistic studies are needed to establish this hypothesis, the authors said.

To evaluate six-year MRI and brain volume loss outcomes in a subset of patient with highly active disease at baseline who were treated with alemtuzumab, Dr. Traboulsee and colleagues analyzed data from the CARE-MS I trial. In that trial, researchers randomized patients with active relapsing-remitting MS who were drug-naïve at baseline to alemtuzumab or interferon beta-1a. After two years, patients who received alemtuzumab had improved clinical and MRI outcomes, including brain loss volume, compared with patients who received interferon beta-1a. In addition, significantly more of these patients had no evidence of disease activity, compared with patients treated with interferon beta1-a.

In an extension study, patients could receive additional treatment with alemtuzumab (12 mg/day on three consecutive days one year or more after the most recent course) as needed for relapse or radiologic activity. During the extension, patients also could receive treatment with other licensed disease-modifying therapies at an investigator’s discretion. Retreatment criteria included one or more relapse, two or more new or enlarging T2 hyperintense lesions, or new gadolinium-enhancing T1 brain or spinal cord lesions on MRI. Researchers defined highly active disease as two or more relapses a year prior to randomization and one or more gadolinium-enhancing T1 lesion at core study baseline.

The researchers obtained MRI scans at baseline and yearly thereafter. Experts masked to patients’ original treatment group assignment analyzed the MRI scans. Investigators assessed the proportion of patients free of MRI disease activity (ie, no new or enlarging T2 hyperintense lesions or new gadolinium-enhancing T1 lesions) and the proportion of patients free of new non-enhancing T1 lesions. Brain volume loss was derived by brain parenchymal fraction change.

Of 376 patients who received alemtuzumab in the CARE-MS I trial, 105 met the criteria for highly active disease at core study baseline. Of these 105 patients, 99 remained in the study through Year 6. Through six years, 63% of patients did not receive additional treatment with alemtuzumab or another disease-modifying therapy. In each year through Year 6, a majority of patients were free of MRI disease activity (61 % at Year 6), free of new gadolinium-enhancing T1 lesions (83% at Year 6), and free of new or enlarging T2 hyperintense lesions (62% at Year 6). The investigators also observed that annually in Years 2 through 6, high proportions of patients had no new non-enhancing T1 hypointense lesions.

“These findings, along with long-term clinical efficacy, suggest that alemtuzumab may provide a unique treatment approach for relapsing-remitting MS patients with highly active disease, offering durable efficacy in the absence of continuous treatment,” said Dr. Traboulsee and colleagues.

NEW ORLEANS—Most patients with relapsing-remitting multiple sclerosis (MS) with highly active disease remain free of new MRI activity for six years after receiving alemtuzumab, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. The durable effects may result from the distinct pattern of lymphocyte repopulation following treatment with alemtuzumab, which may lead to a rebalancing of the immune system, said Anthony Traboulsee, MD, Associate Professor of Neurology at the University of British Columbia in Vancouver. Additional mechanistic studies are needed to establish this hypothesis, the authors said.

To evaluate six-year MRI and brain volume loss outcomes in a subset of patient with highly active disease at baseline who were treated with alemtuzumab, Dr. Traboulsee and colleagues analyzed data from the CARE-MS I trial. In that trial, researchers randomized patients with active relapsing-remitting MS who were drug-naïve at baseline to alemtuzumab or interferon beta-1a. After two years, patients who received alemtuzumab had improved clinical and MRI outcomes, including brain loss volume, compared with patients who received interferon beta-1a. In addition, significantly more of these patients had no evidence of disease activity, compared with patients treated with interferon beta1-a.

In an extension study, patients could receive additional treatment with alemtuzumab (12 mg/day on three consecutive days one year or more after the most recent course) as needed for relapse or radiologic activity. During the extension, patients also could receive treatment with other licensed disease-modifying therapies at an investigator’s discretion. Retreatment criteria included one or more relapse, two or more new or enlarging T2 hyperintense lesions, or new gadolinium-enhancing T1 brain or spinal cord lesions on MRI. Researchers defined highly active disease as two or more relapses a year prior to randomization and one or more gadolinium-enhancing T1 lesion at core study baseline.

The researchers obtained MRI scans at baseline and yearly thereafter. Experts masked to patients’ original treatment group assignment analyzed the MRI scans. Investigators assessed the proportion of patients free of MRI disease activity (ie, no new or enlarging T2 hyperintense lesions or new gadolinium-enhancing T1 lesions) and the proportion of patients free of new non-enhancing T1 lesions. Brain volume loss was derived by brain parenchymal fraction change.

Of 376 patients who received alemtuzumab in the CARE-MS I trial, 105 met the criteria for highly active disease at core study baseline. Of these 105 patients, 99 remained in the study through Year 6. Through six years, 63% of patients did not receive additional treatment with alemtuzumab or another disease-modifying therapy. In each year through Year 6, a majority of patients were free of MRI disease activity (61 % at Year 6), free of new gadolinium-enhancing T1 lesions (83% at Year 6), and free of new or enlarging T2 hyperintense lesions (62% at Year 6). The investigators also observed that annually in Years 2 through 6, high proportions of patients had no new non-enhancing T1 hypointense lesions.

“These findings, along with long-term clinical efficacy, suggest that alemtuzumab may provide a unique treatment approach for relapsing-remitting MS patients with highly active disease, offering durable efficacy in the absence of continuous treatment,” said Dr. Traboulsee and colleagues.

NEW ORLEANS—Two studies presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis (MS) Centers examined the impact of MS and treatment among patients who are members of an online social network. Researchers found that, among patients who were taking oral disease-modifying treatments (DMTs), how the drug was taken was the most important factor in selecting the therapy (36% of patients) almost as often as the doctor’s recommendation (40% of patients), according to the results of a patient survey. In a separate study that analyzed comments made on the social network, researchers found that adverse events were the most commonly stated reason for stopping a treatment (56%).

In one study, Terrie Livingston, PharmD, an employee of Biogen in Weston, Massachusetts, and colleagues conducted a patient survey to assess the impact of MS on day-to-day life, self-reported symptoms, patient descriptions of disability progression, trade-offs when deciding which DMT to take, and what health care providers should know to better manage MS.

In November 2014, researchers sent an email invitation to the entire MyMSTeam community, a social network of approximately 25,000 people (currently more than 75,000 people) diagnosed with MS. In all, 1,107 members responded to the survey.

Overall, the most commonly reported symptoms were fatigue (82% of patients), problems with mobility (64%), and poor balance (64%). In addition, weakness, cognitive issues, and depression were common. The respondents defined disability progression as increased limitations on their ability to get around, having to sacrifice normal daily activities, and losing their ability to be independent. Patients measured the efficacy of DMTs by evaluating the treatments’ ability to slow progression, prevent further physical disability, prevent new lesions, and improve quality of life.

In a separate study, Dr. Livingston and colleagues conducted an analysis of organic discussions within MyMSTeam from January 2015 to April 2016. Researchers anonymized, coded, categorized, and analyzed 3,300 verbatim comments by key themes. The analysis focused on 12 DMTs. Discussions were overlaid with patient self-reported data on gender, age, date of diagnosis, MS type, current DMT, and effectiveness ratings.

Common discussion topics included side effects experienced; reasons for stopping treatment; perceived efficacy; questions, hopes, and concerns about starting a new DMT; rituals to mitigate side effects; and insurance or financial hurdles to getting on or staying on treatment.

Discussions about infusion therapies tended to focus on receiving treatment and issues related to progressive multifocal leukoencephalopathy.

When discussing Tysabri (natalizumab), patients most commonly discussed elevated energy levels post infusion around day 14. Patients also reported increased fatigue in the days prior to the next infusion and extreme fatigue on the day of treatment. In addition, patients shared their experiences with managing tolerability issues, most commonly flu-like symptoms with interferons and gastrointestinal effects with Tecfidera (dimethyl fumarate).

Dr. Livingston and colleagues said that their research “will better allow medical professionals to treat the individual holistically, and not just the disease itself. Additionally, helping patients understand MS progression will allow specialists to set realistic expectations for treating the disease and to help their patients better prepare for the future.”

NEW ORLEANS—Two studies presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis (MS) Centers examined the impact of MS and treatment among patients who are members of an online social network. Researchers found that, among patients who were taking oral disease-modifying treatments (DMTs), how the drug was taken was the most important factor in selecting the therapy (36% of patients) almost as often as the doctor’s recommendation (40% of patients), according to the results of a patient survey. In a separate study that analyzed comments made on the social network, researchers found that adverse events were the most commonly stated reason for stopping a treatment (56%).

In one study, Terrie Livingston, PharmD, an employee of Biogen in Weston, Massachusetts, and colleagues conducted a patient survey to assess the impact of MS on day-to-day life, self-reported symptoms, patient descriptions of disability progression, trade-offs when deciding which DMT to take, and what health care providers should know to better manage MS.

In November 2014, researchers sent an email invitation to the entire MyMSTeam community, a social network of approximately 25,000 people (currently more than 75,000 people) diagnosed with MS. In all, 1,107 members responded to the survey.

Overall, the most commonly reported symptoms were fatigue (82% of patients), problems with mobility (64%), and poor balance (64%). In addition, weakness, cognitive issues, and depression were common. The respondents defined disability progression as increased limitations on their ability to get around, having to sacrifice normal daily activities, and losing their ability to be independent. Patients measured the efficacy of DMTs by evaluating the treatments’ ability to slow progression, prevent further physical disability, prevent new lesions, and improve quality of life.

In a separate study, Dr. Livingston and colleagues conducted an analysis of organic discussions within MyMSTeam from January 2015 to April 2016. Researchers anonymized, coded, categorized, and analyzed 3,300 verbatim comments by key themes. The analysis focused on 12 DMTs. Discussions were overlaid with patient self-reported data on gender, age, date of diagnosis, MS type, current DMT, and effectiveness ratings.

Common discussion topics included side effects experienced; reasons for stopping treatment; perceived efficacy; questions, hopes, and concerns about starting a new DMT; rituals to mitigate side effects; and insurance or financial hurdles to getting on or staying on treatment.

Discussions about infusion therapies tended to focus on receiving treatment and issues related to progressive multifocal leukoencephalopathy.

When discussing Tysabri (natalizumab), patients most commonly discussed elevated energy levels post infusion around day 14. Patients also reported increased fatigue in the days prior to the next infusion and extreme fatigue on the day of treatment. In addition, patients shared their experiences with managing tolerability issues, most commonly flu-like symptoms with interferons and gastrointestinal effects with Tecfidera (dimethyl fumarate).

Dr. Livingston and colleagues said that their research “will better allow medical professionals to treat the individual holistically, and not just the disease itself. Additionally, helping patients understand MS progression will allow specialists to set realistic expectations for treating the disease and to help their patients better prepare for the future.”

NEW ORLEANS—Two studies presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis (MS) Centers examined the impact of MS and treatment among patients who are members of an online social network. Researchers found that, among patients who were taking oral disease-modifying treatments (DMTs), how the drug was taken was the most important factor in selecting the therapy (36% of patients) almost as often as the doctor’s recommendation (40% of patients), according to the results of a patient survey. In a separate study that analyzed comments made on the social network, researchers found that adverse events were the most commonly stated reason for stopping a treatment (56%).

In one study, Terrie Livingston, PharmD, an employee of Biogen in Weston, Massachusetts, and colleagues conducted a patient survey to assess the impact of MS on day-to-day life, self-reported symptoms, patient descriptions of disability progression, trade-offs when deciding which DMT to take, and what health care providers should know to better manage MS.

In November 2014, researchers sent an email invitation to the entire MyMSTeam community, a social network of approximately 25,000 people (currently more than 75,000 people) diagnosed with MS. In all, 1,107 members responded to the survey.

Overall, the most commonly reported symptoms were fatigue (82% of patients), problems with mobility (64%), and poor balance (64%). In addition, weakness, cognitive issues, and depression were common. The respondents defined disability progression as increased limitations on their ability to get around, having to sacrifice normal daily activities, and losing their ability to be independent. Patients measured the efficacy of DMTs by evaluating the treatments’ ability to slow progression, prevent further physical disability, prevent new lesions, and improve quality of life.

In a separate study, Dr. Livingston and colleagues conducted an analysis of organic discussions within MyMSTeam from January 2015 to April 2016. Researchers anonymized, coded, categorized, and analyzed 3,300 verbatim comments by key themes. The analysis focused on 12 DMTs. Discussions were overlaid with patient self-reported data on gender, age, date of diagnosis, MS type, current DMT, and effectiveness ratings.

Common discussion topics included side effects experienced; reasons for stopping treatment; perceived efficacy; questions, hopes, and concerns about starting a new DMT; rituals to mitigate side effects; and insurance or financial hurdles to getting on or staying on treatment.

Discussions about infusion therapies tended to focus on receiving treatment and issues related to progressive multifocal leukoencephalopathy.

When discussing Tysabri (natalizumab), patients most commonly discussed elevated energy levels post infusion around day 14. Patients also reported increased fatigue in the days prior to the next infusion and extreme fatigue on the day of treatment. In addition, patients shared their experiences with managing tolerability issues, most commonly flu-like symptoms with interferons and gastrointestinal effects with Tecfidera (dimethyl fumarate).

Dr. Livingston and colleagues said that their research “will better allow medical professionals to treat the individual holistically, and not just the disease itself. Additionally, helping patients understand MS progression will allow specialists to set realistic expectations for treating the disease and to help their patients better prepare for the future.”

BOSTON—Siponimod reduces the risk of three-month and six-month confirmed disability progression in patients with secondary progressive multiple sclerosis (MS), according to research described at the 69th Annual Meeting of the American Academy of Neurology. The treatment also appears to reduce relapse rate and the number of new lesions. The study is “the largest controlled double-blind study in secondary progressive MS,” according to Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland.

Siponimod is a selective sphingosine 1-phosphate receptor-1 and -5 modulator with effects on the CNS and the peripheral nervous system. The treatment may have effects related to remyelination and neuroprotection, according to Dr. Kappos. He and his colleagues conducted a randomized, double-blind, placebo-controlled, phase III study to compare the effects of siponimod and placebo in patients with secondary progressive MS. The investigators randomized patients 2:1 to once-daily siponimod (2 mg) or placebo. Patients were treated for as long as three years in the double-blind phase of the study. In a subsequent extension study, participants were treated for as long as seven years.

The event- and exposure-driven study's primary end point was time to three-month confirmed disability progression, as assessed by the Expanded Disability Status Scale (EDSS). Key secondary end points included time to confirmed worsening of 20% or more from baseline in the Timed 25-Foot Walk test (T25FW) and T2 lesion volume change from baseline. Other secondary end points included six-month confirmed disability progression, annualized relapse rate, 12-item MS Walking Scale (MSWS-12), number of T1 gadolinium-enhancing and T2 lesions, and percent brain volume change.

The investigators randomized 1,651 patients. The population's mean age was 50, and mean EDSS score was 5.5. The sample was typical of the population of patients with secondary progressive MS.

Siponimod reduced the risk of three-month confirmed disability progression by 21% versus placebo. Dr. Kappos and colleagues consistently observed point estimates in favor of siponimod across predefined subgroups, including patients with no relapses in the two years before study initiation and patients without gadolinium-enhancing lesions at baseline.

The risk reduction observed for the T25FW was 6.2%, but was not statistically significant. Siponimod reduced the risk of six-month confirmed disability progression by 26%. In addition, siponimod reduced the annualized relapse rate by 55.5%, the number of T1 gadolinium-enhancing lesions by 86.6%, and the number of new T2 lesions by 81%. The relative differences in change from baseline in T2 lesion volume, MSWS-12, and percent brain volume change were 79.1%, 39.7%, and 23.4%, respectively, versus placebo. Siponimod's effects were more pronounced in patients with relapses at baseline, compared with those without, said Dr. Kappos.

—Erik Greb

BOSTON—Siponimod reduces the risk of three-month and six-month confirmed disability progression in patients with secondary progressive multiple sclerosis (MS), according to research described at the 69th Annual Meeting of the American Academy of Neurology. The treatment also appears to reduce relapse rate and the number of new lesions. The study is “the largest controlled double-blind study in secondary progressive MS,” according to Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland.

Siponimod is a selective sphingosine 1-phosphate receptor-1 and -5 modulator with effects on the CNS and the peripheral nervous system. The treatment may have effects related to remyelination and neuroprotection, according to Dr. Kappos. He and his colleagues conducted a randomized, double-blind, placebo-controlled, phase III study to compare the effects of siponimod and placebo in patients with secondary progressive MS. The investigators randomized patients 2:1 to once-daily siponimod (2 mg) or placebo. Patients were treated for as long as three years in the double-blind phase of the study. In a subsequent extension study, participants were treated for as long as seven years.

The event- and exposure-driven study's primary end point was time to three-month confirmed disability progression, as assessed by the Expanded Disability Status Scale (EDSS). Key secondary end points included time to confirmed worsening of 20% or more from baseline in the Timed 25-Foot Walk test (T25FW) and T2 lesion volume change from baseline. Other secondary end points included six-month confirmed disability progression, annualized relapse rate, 12-item MS Walking Scale (MSWS-12), number of T1 gadolinium-enhancing and T2 lesions, and percent brain volume change.

The investigators randomized 1,651 patients. The population's mean age was 50, and mean EDSS score was 5.5. The sample was typical of the population of patients with secondary progressive MS.

Siponimod reduced the risk of three-month confirmed disability progression by 21% versus placebo. Dr. Kappos and colleagues consistently observed point estimates in favor of siponimod across predefined subgroups, including patients with no relapses in the two years before study initiation and patients without gadolinium-enhancing lesions at baseline.

The risk reduction observed for the T25FW was 6.2%, but was not statistically significant. Siponimod reduced the risk of six-month confirmed disability progression by 26%. In addition, siponimod reduced the annualized relapse rate by 55.5%, the number of T1 gadolinium-enhancing lesions by 86.6%, and the number of new T2 lesions by 81%. The relative differences in change from baseline in T2 lesion volume, MSWS-12, and percent brain volume change were 79.1%, 39.7%, and 23.4%, respectively, versus placebo. Siponimod's effects were more pronounced in patients with relapses at baseline, compared with those without, said Dr. Kappos.

—Erik Greb

BOSTON—Siponimod reduces the risk of three-month and six-month confirmed disability progression in patients with secondary progressive multiple sclerosis (MS), according to research described at the 69th Annual Meeting of the American Academy of Neurology. The treatment also appears to reduce relapse rate and the number of new lesions. The study is “the largest controlled double-blind study in secondary progressive MS,” according to Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland.

Siponimod is a selective sphingosine 1-phosphate receptor-1 and -5 modulator with effects on the CNS and the peripheral nervous system. The treatment may have effects related to remyelination and neuroprotection, according to Dr. Kappos. He and his colleagues conducted a randomized, double-blind, placebo-controlled, phase III study to compare the effects of siponimod and placebo in patients with secondary progressive MS. The investigators randomized patients 2:1 to once-daily siponimod (2 mg) or placebo. Patients were treated for as long as three years in the double-blind phase of the study. In a subsequent extension study, participants were treated for as long as seven years.

The event- and exposure-driven study's primary end point was time to three-month confirmed disability progression, as assessed by the Expanded Disability Status Scale (EDSS). Key secondary end points included time to confirmed worsening of 20% or more from baseline in the Timed 25-Foot Walk test (T25FW) and T2 lesion volume change from baseline. Other secondary end points included six-month confirmed disability progression, annualized relapse rate, 12-item MS Walking Scale (MSWS-12), number of T1 gadolinium-enhancing and T2 lesions, and percent brain volume change.

The investigators randomized 1,651 patients. The population's mean age was 50, and mean EDSS score was 5.5. The sample was typical of the population of patients with secondary progressive MS.

Siponimod reduced the risk of three-month confirmed disability progression by 21% versus placebo. Dr. Kappos and colleagues consistently observed point estimates in favor of siponimod across predefined subgroups, including patients with no relapses in the two years before study initiation and patients without gadolinium-enhancing lesions at baseline.

The risk reduction observed for the T25FW was 6.2%, but was not statistically significant. Siponimod reduced the risk of six-month confirmed disability progression by 26%. In addition, siponimod reduced the annualized relapse rate by 55.5%, the number of T1 gadolinium-enhancing lesions by 86.6%, and the number of new T2 lesions by 81%. The relative differences in change from baseline in T2 lesion volume, MSWS-12, and percent brain volume change were 79.1%, 39.7%, and 23.4%, respectively, versus placebo. Siponimod's effects were more pronounced in patients with relapses at baseline, compared with those without, said Dr. Kappos.

—Erik Greb

BOSTON—In older people with multiple sclerosis (MS), fatigue and limited lower leg function are more common in people with MS progression than in those without, according to a preliminary study presented at the 69th Annual Meeting of the American Academy of Neurology.

“Study participants with those symptoms were more likely to progress from relapsing-remitting MS to secondary progressive MS within five years,” said study author Bianca Weinstock-Guttman, MD, a Professor in the Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo in New York. “Better understanding of who is at high risk of getting worse may eventually allow us to tailor more specific treatments to these people.”

Older age at disease onset, high frequency of relapses, and male sex have been found to be predictive of higher risk of conversion to secondary progressive MS. To further define predictors of disease progression, Dr. Weinstock-Guttman and colleagues investigated patient-reported outcomes in an aging cohort of patients with MS.

For the study, 155 people age 50 or older who had had relapsing-remitting MS for at least 15 years were evaluated for symptoms and level of disability at the beginning of the study and five years later, at which point they had been living with MS for an average of 22 years. The study subjects were part of the New York State MS Consortium.

In all, 30.3% of people in the study had progressed to secondary progressive MS by the five-year mark. Those who progressed to secondary progressive MS were older at study enrollment (54.8 vs 52.1) and had a higher Expanded Disability Status Scale score at baseline (3.5 vs 2.6) and at year 5 (5.6 vs 3.0). Those who progressed at year 5 were more likely to report lower limb problems at baseline (53.2% vs 21.5%; odds ratio, 3.0) and were more likely to report fatigue (91.5% vs 68.2%; odds ratio, 4.2), compared with those whose disease did not progress. The results were the same after researchers adjusted for other factors that could affect disease progression, such as age, disease duration, and disability severity.

“While more research needs to be done, this study brings us closer to understanding which older adults with MS may be at higher risk of getting worse,” said Dr. Weinstock-Guttman. “With the aging population, this information will be vital as people with MS, their families, and policy makers make decisions about their care.” The investigation was supported by the National MS Society.

—Glenn S. Williams

BOSTON—In older people with multiple sclerosis (MS), fatigue and limited lower leg function are more common in people with MS progression than in those without, according to a preliminary study presented at the 69th Annual Meeting of the American Academy of Neurology.

“Study participants with those symptoms were more likely to progress from relapsing-remitting MS to secondary progressive MS within five years,” said study author Bianca Weinstock-Guttman, MD, a Professor in the Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo in New York. “Better understanding of who is at high risk of getting worse may eventually allow us to tailor more specific treatments to these people.”

Older age at disease onset, high frequency of relapses, and male sex have been found to be predictive of higher risk of conversion to secondary progressive MS. To further define predictors of disease progression, Dr. Weinstock-Guttman and colleagues investigated patient-reported outcomes in an aging cohort of patients with MS.

For the study, 155 people age 50 or older who had had relapsing-remitting MS for at least 15 years were evaluated for symptoms and level of disability at the beginning of the study and five years later, at which point they had been living with MS for an average of 22 years. The study subjects were part of the New York State MS Consortium.

In all, 30.3% of people in the study had progressed to secondary progressive MS by the five-year mark. Those who progressed to secondary progressive MS were older at study enrollment (54.8 vs 52.1) and had a higher Expanded Disability Status Scale score at baseline (3.5 vs 2.6) and at year 5 (5.6 vs 3.0). Those who progressed at year 5 were more likely to report lower limb problems at baseline (53.2% vs 21.5%; odds ratio, 3.0) and were more likely to report fatigue (91.5% vs 68.2%; odds ratio, 4.2), compared with those whose disease did not progress. The results were the same after researchers adjusted for other factors that could affect disease progression, such as age, disease duration, and disability severity.

“While more research needs to be done, this study brings us closer to understanding which older adults with MS may be at higher risk of getting worse,” said Dr. Weinstock-Guttman. “With the aging population, this information will be vital as people with MS, their families, and policy makers make decisions about their care.” The investigation was supported by the National MS Society.

—Glenn S. Williams

BOSTON—In older people with multiple sclerosis (MS), fatigue and limited lower leg function are more common in people with MS progression than in those without, according to a preliminary study presented at the 69th Annual Meeting of the American Academy of Neurology.

“Study participants with those symptoms were more likely to progress from relapsing-remitting MS to secondary progressive MS within five years,” said study author Bianca Weinstock-Guttman, MD, a Professor in the Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo in New York. “Better understanding of who is at high risk of getting worse may eventually allow us to tailor more specific treatments to these people.”

Older age at disease onset, high frequency of relapses, and male sex have been found to be predictive of higher risk of conversion to secondary progressive MS. To further define predictors of disease progression, Dr. Weinstock-Guttman and colleagues investigated patient-reported outcomes in an aging cohort of patients with MS.

For the study, 155 people age 50 or older who had had relapsing-remitting MS for at least 15 years were evaluated for symptoms and level of disability at the beginning of the study and five years later, at which point they had been living with MS for an average of 22 years. The study subjects were part of the New York State MS Consortium.

In all, 30.3% of people in the study had progressed to secondary progressive MS by the five-year mark. Those who progressed to secondary progressive MS were older at study enrollment (54.8 vs 52.1) and had a higher Expanded Disability Status Scale score at baseline (3.5 vs 2.6) and at year 5 (5.6 vs 3.0). Those who progressed at year 5 were more likely to report lower limb problems at baseline (53.2% vs 21.5%; odds ratio, 3.0) and were more likely to report fatigue (91.5% vs 68.2%; odds ratio, 4.2), compared with those whose disease did not progress. The results were the same after researchers adjusted for other factors that could affect disease progression, such as age, disease duration, and disability severity.

“While more research needs to be done, this study brings us closer to understanding which older adults with MS may be at higher risk of getting worse,” said Dr. Weinstock-Guttman. “With the aging population, this information will be vital as people with MS, their families, and policy makers make decisions about their care.” The investigation was supported by the National MS Society.

—Glenn S. Williams

BOSTON—Interim results from a small, preliminary study support a new type of treatment for progressive multiple sclerosis (MS). Results from the first six people enrolled in the phase I study, which was designed to enroll 10 people, were presented at the 69th Annual Meeting of the American Academy of Neurology. “While these results are very preliminary, and much more research is needed, we are excited there were no serious side effects,” said study author Michael P. Pender, MD, PhD, a Professor and Director of the Multiple Sclerosis Research Group at the University of Queensland in Brisbane, Australia.

The study investigated the relationship between MS and the Epstein-Barr virus (EBV). Previous research has suggested a role for EBV in MS pathogenesis. The study involved six people with progressive MS who had moderate to severe disability (ie, Expanded Disability Status Scale scores between 5.0 and 8.0).

In some people with MS, EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T-cell immunity. Elimination of EBV-infected B cells may reduce the destruction of myelin in MS.

For the study, researchers removed the participants' own T cells and stimulated them to boost their ability to recognize and destroy cells infected with EBV. They then injected participants with infusions of escalating doses of T cells every two weeks for six weeks. They followed the patients for 26 weeks to look for evidence of side effects and possible improvement of symptoms.

Three participants showed symptomatic and objective clinical improvement, starting two to eight weeks after the first infusion.

“One person with secondary progressive MS showed striking improvement,” Professor Pender said. This participant had normalization of lower extremity tone and plantar responses for the first time in 16 years. “This participant had a significant increase in ambulation from 100 yards with a walker at the start of the study, and over the previous five years, to three quarters of a mile, and was now also able to walk shorter distances with only one-sided assistance. Lower leg spasms that had persisted for years resolved.”

Professor Pender said another participant with primary progressive MS had reduced fatigue, increased productivity, and improved balance. Another responder had improved color vision, visual acuity, and manual dexterity; reduced fatigue; fewer lower extremity spasms; and less urinary urgency. All three responding participants had improvements in fatigue and ability to perform daily activities.  

“The best responses were seen in the two people who received T cells with the highest amount of reactivity to the EBV,” Professor Pender said. None of the six participants had serious side effects.

“Much more research needs to be done with larger numbers of participants to confirm and further evaluate these findings,” Professor Pender said. “But the results add to the mounting evidence for a role of the Epstein-Barr virus infection in MS and set the stage for further clinical trials.”

The study was a collaboration between the QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, and the University of Queensland. The study was supported by MS Queensland, MS Research Australia, QIMR Berghofer Medical Research Institute, and Perpetual Trustee Company Limited.    

—Glenn S. Williams

Suggested Reading

Pender MP, Csurhes PA, Smith C, et al. Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis. Mult Scler. 2014;20(11):1541-1544.

BOSTON—Interim results from a small, preliminary study support a new type of treatment for progressive multiple sclerosis (MS). Results from the first six people enrolled in the phase I study, which was designed to enroll 10 people, were presented at the 69th Annual Meeting of the American Academy of Neurology. “While these results are very preliminary, and much more research is needed, we are excited there were no serious side effects,” said study author Michael P. Pender, MD, PhD, a Professor and Director of the Multiple Sclerosis Research Group at the University of Queensland in Brisbane, Australia.

The study investigated the relationship between MS and the Epstein-Barr virus (EBV). Previous research has suggested a role for EBV in MS pathogenesis. The study involved six people with progressive MS who had moderate to severe disability (ie, Expanded Disability Status Scale scores between 5.0 and 8.0).

In some people with MS, EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T-cell immunity. Elimination of EBV-infected B cells may reduce the destruction of myelin in MS.

For the study, researchers removed the participants' own T cells and stimulated them to boost their ability to recognize and destroy cells infected with EBV. They then injected participants with infusions of escalating doses of T cells every two weeks for six weeks. They followed the patients for 26 weeks to look for evidence of side effects and possible improvement of symptoms.

Three participants showed symptomatic and objective clinical improvement, starting two to eight weeks after the first infusion.

“One person with secondary progressive MS showed striking improvement,” Professor Pender said. This participant had normalization of lower extremity tone and plantar responses for the first time in 16 years. “This participant had a significant increase in ambulation from 100 yards with a walker at the start of the study, and over the previous five years, to three quarters of a mile, and was now also able to walk shorter distances with only one-sided assistance. Lower leg spasms that had persisted for years resolved.”

Professor Pender said another participant with primary progressive MS had reduced fatigue, increased productivity, and improved balance. Another responder had improved color vision, visual acuity, and manual dexterity; reduced fatigue; fewer lower extremity spasms; and less urinary urgency. All three responding participants had improvements in fatigue and ability to perform daily activities.  

“The best responses were seen in the two people who received T cells with the highest amount of reactivity to the EBV,” Professor Pender said. None of the six participants had serious side effects.

“Much more research needs to be done with larger numbers of participants to confirm and further evaluate these findings,” Professor Pender said. “But the results add to the mounting evidence for a role of the Epstein-Barr virus infection in MS and set the stage for further clinical trials.”

The study was a collaboration between the QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, and the University of Queensland. The study was supported by MS Queensland, MS Research Australia, QIMR Berghofer Medical Research Institute, and Perpetual Trustee Company Limited.    

—Glenn S. Williams

Suggested Reading

Pender MP, Csurhes PA, Smith C, et al. Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis. Mult Scler. 2014;20(11):1541-1544.

BOSTON—Interim results from a small, preliminary study support a new type of treatment for progressive multiple sclerosis (MS). Results from the first six people enrolled in the phase I study, which was designed to enroll 10 people, were presented at the 69th Annual Meeting of the American Academy of Neurology. “While these results are very preliminary, and much more research is needed, we are excited there were no serious side effects,” said study author Michael P. Pender, MD, PhD, a Professor and Director of the Multiple Sclerosis Research Group at the University of Queensland in Brisbane, Australia.

The study investigated the relationship between MS and the Epstein-Barr virus (EBV). Previous research has suggested a role for EBV in MS pathogenesis. The study involved six people with progressive MS who had moderate to severe disability (ie, Expanded Disability Status Scale scores between 5.0 and 8.0).

In some people with MS, EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T-cell immunity. Elimination of EBV-infected B cells may reduce the destruction of myelin in MS.

For the study, researchers removed the participants' own T cells and stimulated them to boost their ability to recognize and destroy cells infected with EBV. They then injected participants with infusions of escalating doses of T cells every two weeks for six weeks. They followed the patients for 26 weeks to look for evidence of side effects and possible improvement of symptoms.

Three participants showed symptomatic and objective clinical improvement, starting two to eight weeks after the first infusion.

“One person with secondary progressive MS showed striking improvement,” Professor Pender said. This participant had normalization of lower extremity tone and plantar responses for the first time in 16 years. “This participant had a significant increase in ambulation from 100 yards with a walker at the start of the study, and over the previous five years, to three quarters of a mile, and was now also able to walk shorter distances with only one-sided assistance. Lower leg spasms that had persisted for years resolved.”

Professor Pender said another participant with primary progressive MS had reduced fatigue, increased productivity, and improved balance. Another responder had improved color vision, visual acuity, and manual dexterity; reduced fatigue; fewer lower extremity spasms; and less urinary urgency. All three responding participants had improvements in fatigue and ability to perform daily activities.  

“The best responses were seen in the two people who received T cells with the highest amount of reactivity to the EBV,” Professor Pender said. None of the six participants had serious side effects.

“Much more research needs to be done with larger numbers of participants to confirm and further evaluate these findings,” Professor Pender said. “But the results add to the mounting evidence for a role of the Epstein-Barr virus infection in MS and set the stage for further clinical trials.”

The study was a collaboration between the QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, and the University of Queensland. The study was supported by MS Queensland, MS Research Australia, QIMR Berghofer Medical Research Institute, and Perpetual Trustee Company Limited.    

—Glenn S. Williams

Suggested Reading

Pender MP, Csurhes PA, Smith C, et al. Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis. Mult Scler. 2014;20(11):1541-1544.

NEW ORLEANS—Immunizing patients on B cell–depleting therapies against influenza using the inactivated virus vaccine may be beneficial, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Creating virus-specific T cell immunity and boosting highly cross-reactive memory T cells from prior exposures to influenza are valuable in reducing the severity of the infection,” said Elena Grebenciucova, MD, and Eric Williamson, MD, of the Multiple Sclerosis Division of the Perelman Center for Advanced Medicine at the University of Pennsylvania in Philadelphia.

The use of B cell–depleting therapies in patients with multiple sclerosis, neuromyelitis optica, and other inflammatory disorders raises a clinical dilemma. Given that the ability to generate an adequate protective antibody response is severely impaired due to B-cell depletion, is it still beneficial to immunize patients using the inactivated influenza vaccine? The practice of vaccinating patients on B cell–depleting therapies is not universal among neurologists. Many assume that the practice has no benefit and choose not to vaccinate their patients. However, antibody-mediated immune responses are not the only part of the immune system that helps control influenza infection. T cell–mediated immunity, although affected by the absence of B cells in many complex ways, is not abolished, and may offer protection, limit severity of the disease, and reduce influenza-associated morbidity.

Drs. Grebenciucova and Williamson conducted a literature review and analysis to provide a mechanistic rationale for immunizing against influenza in patients on B cell–depleting therapies.

In 2008, Stambas et al reported that virus-specific CD8+ T effector cells are important in clearing influenza infection. They also found that CD4+ T memory cells are critical in maintaining virus-specific CD8+ memory responses. Influenza vaccine helps prime naïve T cells and generates virus-specific T cells. Vaccinating also can boost pre-existent influenza-specific memory T cells, which, unlike the specific antibodies, are effective against various strains of the virus.

Dolphi et al. showed that memory T cell CD8+ and CD4+ epitopes cross-react with internal viral protein sequences (matrix [M] and nucleoprotein [NP]) that are highly conserved among various influenza strains, and thus may offer protection even when the antibody response is either inadequate or directed against the wrong strain of the virus.

A study by Sridhar et al conducted in the setting of the 2009 H1N1 pandemic highlighted the importance of cross-reactive cellular immunity by evaluating CD8+ T cell responses prior to, during, and after the influenza infection and showed that those with pre-existent CD8+ T cells specific for highly conserved internal viral proteins experienced a less severe illness, despite the absence of neutralizing antibodies.

Wilkinson et al and McElhaney et al also showed that even in the setting of inadequate antibody responses, virus-specific T cell–mediated immunity against influenza virus offers protection and may reduce morbidity.

Suggested Reading

McElhaney JE, Kuchel GA, Zhou X, et al. T-cell immunity to influenza in older adults: a pathophysiological framework for development of more effective vaccines. Front Immunol. 2016;7:41.

Sridhar S, Begom S, Bermingham A, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013;19(10):1305-1312.

Stambas J, Guillonneau C, Kedzierska K, et al. Killer T cells in influenza. Pharmacol Ther. 2008;120(2):186-196.

Wilkinson TM, Li CK, Chui CS, et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med. 2012;18(2):274-280.

NEW ORLEANS—Immunizing patients on B cell–depleting therapies against influenza using the inactivated virus vaccine may be beneficial, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Creating virus-specific T cell immunity and boosting highly cross-reactive memory T cells from prior exposures to influenza are valuable in reducing the severity of the infection,” said Elena Grebenciucova, MD, and Eric Williamson, MD, of the Multiple Sclerosis Division of the Perelman Center for Advanced Medicine at the University of Pennsylvania in Philadelphia.

The use of B cell–depleting therapies in patients with multiple sclerosis, neuromyelitis optica, and other inflammatory disorders raises a clinical dilemma. Given that the ability to generate an adequate protective antibody response is severely impaired due to B-cell depletion, is it still beneficial to immunize patients using the inactivated influenza vaccine? The practice of vaccinating patients on B cell–depleting therapies is not universal among neurologists. Many assume that the practice has no benefit and choose not to vaccinate their patients. However, antibody-mediated immune responses are not the only part of the immune system that helps control influenza infection. T cell–mediated immunity, although affected by the absence of B cells in many complex ways, is not abolished, and may offer protection, limit severity of the disease, and reduce influenza-associated morbidity.

Drs. Grebenciucova and Williamson conducted a literature review and analysis to provide a mechanistic rationale for immunizing against influenza in patients on B cell–depleting therapies.

In 2008, Stambas et al reported that virus-specific CD8+ T effector cells are important in clearing influenza infection. They also found that CD4+ T memory cells are critical in maintaining virus-specific CD8+ memory responses. Influenza vaccine helps prime naïve T cells and generates virus-specific T cells. Vaccinating also can boost pre-existent influenza-specific memory T cells, which, unlike the specific antibodies, are effective against various strains of the virus.

Dolphi et al. showed that memory T cell CD8+ and CD4+ epitopes cross-react with internal viral protein sequences (matrix [M] and nucleoprotein [NP]) that are highly conserved among various influenza strains, and thus may offer protection even when the antibody response is either inadequate or directed against the wrong strain of the virus.

A study by Sridhar et al conducted in the setting of the 2009 H1N1 pandemic highlighted the importance of cross-reactive cellular immunity by evaluating CD8+ T cell responses prior to, during, and after the influenza infection and showed that those with pre-existent CD8+ T cells specific for highly conserved internal viral proteins experienced a less severe illness, despite the absence of neutralizing antibodies.

Wilkinson et al and McElhaney et al also showed that even in the setting of inadequate antibody responses, virus-specific T cell–mediated immunity against influenza virus offers protection and may reduce morbidity.

Suggested Reading

McElhaney JE, Kuchel GA, Zhou X, et al. T-cell immunity to influenza in older adults: a pathophysiological framework for development of more effective vaccines. Front Immunol. 2016;7:41.

Sridhar S, Begom S, Bermingham A, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013;19(10):1305-1312.

Stambas J, Guillonneau C, Kedzierska K, et al. Killer T cells in influenza. Pharmacol Ther. 2008;120(2):186-196.

Wilkinson TM, Li CK, Chui CS, et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med. 2012;18(2):274-280.

NEW ORLEANS—Immunizing patients on B cell–depleting therapies against influenza using the inactivated virus vaccine may be beneficial, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Creating virus-specific T cell immunity and boosting highly cross-reactive memory T cells from prior exposures to influenza are valuable in reducing the severity of the infection,” said Elena Grebenciucova, MD, and Eric Williamson, MD, of the Multiple Sclerosis Division of the Perelman Center for Advanced Medicine at the University of Pennsylvania in Philadelphia.

The use of B cell–depleting therapies in patients with multiple sclerosis, neuromyelitis optica, and other inflammatory disorders raises a clinical dilemma. Given that the ability to generate an adequate protective antibody response is severely impaired due to B-cell depletion, is it still beneficial to immunize patients using the inactivated influenza vaccine? The practice of vaccinating patients on B cell–depleting therapies is not universal among neurologists. Many assume that the practice has no benefit and choose not to vaccinate their patients. However, antibody-mediated immune responses are not the only part of the immune system that helps control influenza infection. T cell–mediated immunity, although affected by the absence of B cells in many complex ways, is not abolished, and may offer protection, limit severity of the disease, and reduce influenza-associated morbidity.

Drs. Grebenciucova and Williamson conducted a literature review and analysis to provide a mechanistic rationale for immunizing against influenza in patients on B cell–depleting therapies.

In 2008, Stambas et al reported that virus-specific CD8+ T effector cells are important in clearing influenza infection. They also found that CD4+ T memory cells are critical in maintaining virus-specific CD8+ memory responses. Influenza vaccine helps prime naïve T cells and generates virus-specific T cells. Vaccinating also can boost pre-existent influenza-specific memory T cells, which, unlike the specific antibodies, are effective against various strains of the virus.

Dolphi et al. showed that memory T cell CD8+ and CD4+ epitopes cross-react with internal viral protein sequences (matrix [M] and nucleoprotein [NP]) that are highly conserved among various influenza strains, and thus may offer protection even when the antibody response is either inadequate or directed against the wrong strain of the virus.

A study by Sridhar et al conducted in the setting of the 2009 H1N1 pandemic highlighted the importance of cross-reactive cellular immunity by evaluating CD8+ T cell responses prior to, during, and after the influenza infection and showed that those with pre-existent CD8+ T cells specific for highly conserved internal viral proteins experienced a less severe illness, despite the absence of neutralizing antibodies.

Wilkinson et al and McElhaney et al also showed that even in the setting of inadequate antibody responses, virus-specific T cell–mediated immunity against influenza virus offers protection and may reduce morbidity.

Suggested Reading

McElhaney JE, Kuchel GA, Zhou X, et al. T-cell immunity to influenza in older adults: a pathophysiological framework for development of more effective vaccines. Front Immunol. 2016;7:41.

Sridhar S, Begom S, Bermingham A, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013;19(10):1305-1312.

Stambas J, Guillonneau C, Kedzierska K, et al. Killer T cells in influenza. Pharmacol Ther. 2008;120(2):186-196.

Wilkinson TM, Li CK, Chui CS, et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med. 2012;18(2):274-280.

NEW ORLEANS—A diet high in fruits, vegetables, legumes, and whole grains and low in sugar and red meat is associated with less disability and fewer depressive symptoms in patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Our findings suggest that people with MS who have a healthier diet have less disability, and that a generally healthy lifestyle is associated with a lower burden of severe depression, pain, fatigue, and cognitive problems. Therefore, modifying diet may offer a way of improving symptoms,” said Ruth Ann Marrie, MD, PhD, Associate Professor of Neurology and Director of the MS Clinic at the University of Manitoba in Winnipeg, Canada.

Many patients with MS ask whether their diet could influence their disease status. To address this question, Dr. Marrie and colleagues assessed the association between overall diet quality and disability and physical and mental functioning in a large cohort of people with MS. They conducted a cross-sectional study of North American Research Committee on MS (NARCOMS) registry participants who had completed a dietary screener questionnaire. The questionnaire, created by the National Health and Nutrition Examination Survey, provides an assessment of diet composition when full information on diet is unavailable. The survey estimates intake of fruits, vegetables and legumes, whole grains, added sugars, and red and processed meats.

The researchers constructed an overall diet-quality score based on responses to the questionnaire and assigned participants to sex-specific quintiles of each of the questionnaire’s five food groups. They then assigned scores for fruits, vegetables, legumes, and whole grains based on the patient’s quintile ranking. The investigators inverted scores for red and processed meats and added sugar. The researchers summed individual food-group scores to obtain an overall diet score, ranging from 4 (poor quality) to 20 (high quality).

Dr. Marrie and colleagues assessed the association between diet quality and disability status (using the Patient-Determined Disease Steps) and mental and physical functioning (ie, depression, fatigue, cognition, mobility, vision, pain, spasticity, tremor, and sensory function) using proportional odds models adjusting for age, gender, income, BMI, smoking status, and disease duration.

In all, 7,418 responders had an average quality-diet score of 11.9. Patients with higher scores tended to be older, leaner, and nonsmokers. People with diet-quality scores in the top quintile had lower levels of disability and lower depression scores. Diet-quality scores were not associated with other physical or mental functioning scores, however.

A lack of details about potentially important dietary factors, such as types of fat, is one limitation of the study, said Dr. Marrie.

“While our study does not prove that diet change will improve symptoms, a high-quality diet that emphasizes intake of fruits, vegetables, and whole grains, and lower intake of red meat, can be encouraged, given the known benefits for general health,” said Dr. Marrie. “Future studies should look at the relationship between diet and disability, as well as symptoms over time, so that we can establish whether changing diet will improve outcomes in MS. These studies should also look at diet in more detail.”

The National MS Society supported this study.

—Erica Tricarico

NEW ORLEANS—A diet high in fruits, vegetables, legumes, and whole grains and low in sugar and red meat is associated with less disability and fewer depressive symptoms in patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Our findings suggest that people with MS who have a healthier diet have less disability, and that a generally healthy lifestyle is associated with a lower burden of severe depression, pain, fatigue, and cognitive problems. Therefore, modifying diet may offer a way of improving symptoms,” said Ruth Ann Marrie, MD, PhD, Associate Professor of Neurology and Director of the MS Clinic at the University of Manitoba in Winnipeg, Canada.

Many patients with MS ask whether their diet could influence their disease status. To address this question, Dr. Marrie and colleagues assessed the association between overall diet quality and disability and physical and mental functioning in a large cohort of people with MS. They conducted a cross-sectional study of North American Research Committee on MS (NARCOMS) registry participants who had completed a dietary screener questionnaire. The questionnaire, created by the National Health and Nutrition Examination Survey, provides an assessment of diet composition when full information on diet is unavailable. The survey estimates intake of fruits, vegetables and legumes, whole grains, added sugars, and red and processed meats.

The researchers constructed an overall diet-quality score based on responses to the questionnaire and assigned participants to sex-specific quintiles of each of the questionnaire’s five food groups. They then assigned scores for fruits, vegetables, legumes, and whole grains based on the patient’s quintile ranking. The investigators inverted scores for red and processed meats and added sugar. The researchers summed individual food-group scores to obtain an overall diet score, ranging from 4 (poor quality) to 20 (high quality).

Dr. Marrie and colleagues assessed the association between diet quality and disability status (using the Patient-Determined Disease Steps) and mental and physical functioning (ie, depression, fatigue, cognition, mobility, vision, pain, spasticity, tremor, and sensory function) using proportional odds models adjusting for age, gender, income, BMI, smoking status, and disease duration.

In all, 7,418 responders had an average quality-diet score of 11.9. Patients with higher scores tended to be older, leaner, and nonsmokers. People with diet-quality scores in the top quintile had lower levels of disability and lower depression scores. Diet-quality scores were not associated with other physical or mental functioning scores, however.

A lack of details about potentially important dietary factors, such as types of fat, is one limitation of the study, said Dr. Marrie.

“While our study does not prove that diet change will improve symptoms, a high-quality diet that emphasizes intake of fruits, vegetables, and whole grains, and lower intake of red meat, can be encouraged, given the known benefits for general health,” said Dr. Marrie. “Future studies should look at the relationship between diet and disability, as well as symptoms over time, so that we can establish whether changing diet will improve outcomes in MS. These studies should also look at diet in more detail.”

The National MS Society supported this study.

—Erica Tricarico

NEW ORLEANS—A diet high in fruits, vegetables, legumes, and whole grains and low in sugar and red meat is associated with less disability and fewer depressive symptoms in patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Our findings suggest that people with MS who have a healthier diet have less disability, and that a generally healthy lifestyle is associated with a lower burden of severe depression, pain, fatigue, and cognitive problems. Therefore, modifying diet may offer a way of improving symptoms,” said Ruth Ann Marrie, MD, PhD, Associate Professor of Neurology and Director of the MS Clinic at the University of Manitoba in Winnipeg, Canada.

Many patients with MS ask whether their diet could influence their disease status. To address this question, Dr. Marrie and colleagues assessed the association between overall diet quality and disability and physical and mental functioning in a large cohort of people with MS. They conducted a cross-sectional study of North American Research Committee on MS (NARCOMS) registry participants who had completed a dietary screener questionnaire. The questionnaire, created by the National Health and Nutrition Examination Survey, provides an assessment of diet composition when full information on diet is unavailable. The survey estimates intake of fruits, vegetables and legumes, whole grains, added sugars, and red and processed meats.

The researchers constructed an overall diet-quality score based on responses to the questionnaire and assigned participants to sex-specific quintiles of each of the questionnaire’s five food groups. They then assigned scores for fruits, vegetables, legumes, and whole grains based on the patient’s quintile ranking. The investigators inverted scores for red and processed meats and added sugar. The researchers summed individual food-group scores to obtain an overall diet score, ranging from 4 (poor quality) to 20 (high quality).

Dr. Marrie and colleagues assessed the association between diet quality and disability status (using the Patient-Determined Disease Steps) and mental and physical functioning (ie, depression, fatigue, cognition, mobility, vision, pain, spasticity, tremor, and sensory function) using proportional odds models adjusting for age, gender, income, BMI, smoking status, and disease duration.

In all, 7,418 responders had an average quality-diet score of 11.9. Patients with higher scores tended to be older, leaner, and nonsmokers. People with diet-quality scores in the top quintile had lower levels of disability and lower depression scores. Diet-quality scores were not associated with other physical or mental functioning scores, however.

A lack of details about potentially important dietary factors, such as types of fat, is one limitation of the study, said Dr. Marrie.

“While our study does not prove that diet change will improve symptoms, a high-quality diet that emphasizes intake of fruits, vegetables, and whole grains, and lower intake of red meat, can be encouraged, given the known benefits for general health,” said Dr. Marrie. “Future studies should look at the relationship between diet and disability, as well as symptoms over time, so that we can establish whether changing diet will improve outcomes in MS. These studies should also look at diet in more detail.”

The National MS Society supported this study.

—Erica Tricarico

NEW ORLEANS—Older adults with multiple sclerosis (MS) who engaged more in light physical activity demonstrated better physical function independent of sedentary behavior and moderate-to-vigorous activity, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Such results might underscore light physical activity as a suitable target of future rehabilitative interventions for improving physical function in older adults with MS,” said Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham.

Rate and pattern of participation in physical activity and sedentary behavior might be associated with a reduction of physical function among older adults with MS. Ms. Cederberg conducted a study that examined the associations among levels of light and moderate-to-vigorous physical activity, sedentary behavior, and physical function in older adults with MS.

Ms. Cederberg’s study sample included 40 older adults with MS with a median age of 60. Participants wore an accelerometer during the waking hours of a seven-day period. In addition, Ms. Cederberg used cut-points for MS to process data for time spent in moderate-to-vigorous physical activity, light physical activity, and sedentary behavior. Finally, patients completed the Short Physical Performance Battery (SPPB), the Six-Minute Walk Test, and the Timed 25-Foot Walk.

The median scores for time spent in moderate-to-vigorous physical activity and light physical activity were lower, and sedentary behavior was significantly greater, than those reported for older adults in the general population.

In addition, bivariate correlation analyses suggested that light physical activity and moderate to vigorous physical activity were associated with SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores, but the association was stronger for light physical activity. Regression analyses yielded significant associations between light physical activity, but not moderate-to-vigorous physical activity or sedentary behavior, and SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores.

NEW ORLEANS—Older adults with multiple sclerosis (MS) who engaged more in light physical activity demonstrated better physical function independent of sedentary behavior and moderate-to-vigorous activity, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Such results might underscore light physical activity as a suitable target of future rehabilitative interventions for improving physical function in older adults with MS,” said Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham.

Rate and pattern of participation in physical activity and sedentary behavior might be associated with a reduction of physical function among older adults with MS. Ms. Cederberg conducted a study that examined the associations among levels of light and moderate-to-vigorous physical activity, sedentary behavior, and physical function in older adults with MS.

Ms. Cederberg’s study sample included 40 older adults with MS with a median age of 60. Participants wore an accelerometer during the waking hours of a seven-day period. In addition, Ms. Cederberg used cut-points for MS to process data for time spent in moderate-to-vigorous physical activity, light physical activity, and sedentary behavior. Finally, patients completed the Short Physical Performance Battery (SPPB), the Six-Minute Walk Test, and the Timed 25-Foot Walk.

The median scores for time spent in moderate-to-vigorous physical activity and light physical activity were lower, and sedentary behavior was significantly greater, than those reported for older adults in the general population.

In addition, bivariate correlation analyses suggested that light physical activity and moderate to vigorous physical activity were associated with SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores, but the association was stronger for light physical activity. Regression analyses yielded significant associations between light physical activity, but not moderate-to-vigorous physical activity or sedentary behavior, and SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores.

NEW ORLEANS—Older adults with multiple sclerosis (MS) who engaged more in light physical activity demonstrated better physical function independent of sedentary behavior and moderate-to-vigorous activity, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Such results might underscore light physical activity as a suitable target of future rehabilitative interventions for improving physical function in older adults with MS,” said Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham.

Rate and pattern of participation in physical activity and sedentary behavior might be associated with a reduction of physical function among older adults with MS. Ms. Cederberg conducted a study that examined the associations among levels of light and moderate-to-vigorous physical activity, sedentary behavior, and physical function in older adults with MS.

Ms. Cederberg’s study sample included 40 older adults with MS with a median age of 60. Participants wore an accelerometer during the waking hours of a seven-day period. In addition, Ms. Cederberg used cut-points for MS to process data for time spent in moderate-to-vigorous physical activity, light physical activity, and sedentary behavior. Finally, patients completed the Short Physical Performance Battery (SPPB), the Six-Minute Walk Test, and the Timed 25-Foot Walk.

The median scores for time spent in moderate-to-vigorous physical activity and light physical activity were lower, and sedentary behavior was significantly greater, than those reported for older adults in the general population.

In addition, bivariate correlation analyses suggested that light physical activity and moderate to vigorous physical activity were associated with SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores, but the association was stronger for light physical activity. Regression analyses yielded significant associations between light physical activity, but not moderate-to-vigorous physical activity or sedentary behavior, and SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores.

NEW ORLEANS—Two-year analyses show that fewer patients required treatment with alemtuzumab than ocrelizumab to prevent one relapse, to prevent relapse in one patient, and to prevent six-month confirmed disability worsening in one patient versus subcutaneous interferon beta-1a, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers.

In the absence of head-to-head trials, researchers can use the number needed to treat to indirectly assess the comparative efficacy of disease-modifying therapies. Aaron L. Boster, MD, and colleagues analyzed the number needed to treat to prevent clinical disease events in studies of alemtuzumab and ocrelizumab in relapsing-remitting multiple sclerosis (MS). Dr. Boster is a clinical neuroimmunologist at the OhioHealth MS Clinic in Columbus.

Number needed to treat values were derived from post hoc analyses of two-year data from studies of alemtuzumab (12 mg) and ocrelizumab (600 mg). Alemtuzumab data were of pooled treatment-naive patients from the CAMMS223 and CARE-MS I studies (n = 786), and separately, patients with inadequate response to prior therapy from CARE-MS II (n = 628). Ocrelizumab data were derived from the OPERA I and II studies (n = 821 and n = 835, respectively). Alemtuzumab was administered as two annual courses; ocrelizumab was administered at baseline and weeks 24, 48, and 72. Number needed to treat was based on inverse of absolute risk differences versus subcutaneous interferon beta-1a 44 μg three times per week (common comparator) for annualized relapse rate and proportion of patients experiencing relapse, and the Altman method for six-month confirmed disability worsening. Lower number needed to treat values reflect greater efficacy.

Baseline mean Expanded Disability Status Scale (EDSS) scores were 2.0 for CAMMS223 and CARE-MS I, 2.7 for CARE-MS II, 2.9 for OPERA I, and 2.8 for OPERA II. Mean MS duration was 1.9 years in CAMMS223 and CARE-MS I, 4.5 years in CARE-MS II, and 6.7 years in OPERA I and II. Mean number of relapses in the previous two years was 2.5 for CAMMS223 and CARE-MS I, 2.8 for CARE-MS II, and 1.8 in OPERA I and II.

Alemtuzumab and ocrelizumab significantly reduced annualized relapse rates and confirmed disability worsening versus subcutaneous interferon beta-1a. Number needed to treat values to prevent one relapse versus subcutaneous interferon beta-1a were lower with alemtuzumab (CAMMS223/CARE-MS I: five; CARE-MS II: four) than with ocrelizumab (OPERA I/II: eight in each study), as were number needed to treat values to prevent one patient from experiencing relapse (CAMMS223/CARE-MS I and CARE-MS II: six in each study; OPERA I and II: eight in each study), and to prevent one patient from experiencing six-month confirmed disability worsening (CAMMS223/CARE-MS I: 15; CARE-MS II: 13; OPERA I: 23; OPERA II: 21).

Although the populations in the available datasets differ, these findings suggest a benefit of alemtuzumab over ocrelizumab.

This study was supported by Sanofi Genzyme.

NEW ORLEANS—Two-year analyses show that fewer patients required treatment with alemtuzumab than ocrelizumab to prevent one relapse, to prevent relapse in one patient, and to prevent six-month confirmed disability worsening in one patient versus subcutaneous interferon beta-1a, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers.

In the absence of head-to-head trials, researchers can use the number needed to treat to indirectly assess the comparative efficacy of disease-modifying therapies. Aaron L. Boster, MD, and colleagues analyzed the number needed to treat to prevent clinical disease events in studies of alemtuzumab and ocrelizumab in relapsing-remitting multiple sclerosis (MS). Dr. Boster is a clinical neuroimmunologist at the OhioHealth MS Clinic in Columbus.

Number needed to treat values were derived from post hoc analyses of two-year data from studies of alemtuzumab (12 mg) and ocrelizumab (600 mg). Alemtuzumab data were of pooled treatment-naive patients from the CAMMS223 and CARE-MS I studies (n = 786), and separately, patients with inadequate response to prior therapy from CARE-MS II (n = 628). Ocrelizumab data were derived from the OPERA I and II studies (n = 821 and n = 835, respectively). Alemtuzumab was administered as two annual courses; ocrelizumab was administered at baseline and weeks 24, 48, and 72. Number needed to treat was based on inverse of absolute risk differences versus subcutaneous interferon beta-1a 44 μg three times per week (common comparator) for annualized relapse rate and proportion of patients experiencing relapse, and the Altman method for six-month confirmed disability worsening. Lower number needed to treat values reflect greater efficacy.

Baseline mean Expanded Disability Status Scale (EDSS) scores were 2.0 for CAMMS223 and CARE-MS I, 2.7 for CARE-MS II, 2.9 for OPERA I, and 2.8 for OPERA II. Mean MS duration was 1.9 years in CAMMS223 and CARE-MS I, 4.5 years in CARE-MS II, and 6.7 years in OPERA I and II. Mean number of relapses in the previous two years was 2.5 for CAMMS223 and CARE-MS I, 2.8 for CARE-MS II, and 1.8 in OPERA I and II.

Alemtuzumab and ocrelizumab significantly reduced annualized relapse rates and confirmed disability worsening versus subcutaneous interferon beta-1a. Number needed to treat values to prevent one relapse versus subcutaneous interferon beta-1a were lower with alemtuzumab (CAMMS223/CARE-MS I: five; CARE-MS II: four) than with ocrelizumab (OPERA I/II: eight in each study), as were number needed to treat values to prevent one patient from experiencing relapse (CAMMS223/CARE-MS I and CARE-MS II: six in each study; OPERA I and II: eight in each study), and to prevent one patient from experiencing six-month confirmed disability worsening (CAMMS223/CARE-MS I: 15; CARE-MS II: 13; OPERA I: 23; OPERA II: 21).

Although the populations in the available datasets differ, these findings suggest a benefit of alemtuzumab over ocrelizumab.

This study was supported by Sanofi Genzyme.

NEW ORLEANS—Two-year analyses show that fewer patients required treatment with alemtuzumab than ocrelizumab to prevent one relapse, to prevent relapse in one patient, and to prevent six-month confirmed disability worsening in one patient versus subcutaneous interferon beta-1a, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers.

In the absence of head-to-head trials, researchers can use the number needed to treat to indirectly assess the comparative efficacy of disease-modifying therapies. Aaron L. Boster, MD, and colleagues analyzed the number needed to treat to prevent clinical disease events in studies of alemtuzumab and ocrelizumab in relapsing-remitting multiple sclerosis (MS). Dr. Boster is a clinical neuroimmunologist at the OhioHealth MS Clinic in Columbus.

Number needed to treat values were derived from post hoc analyses of two-year data from studies of alemtuzumab (12 mg) and ocrelizumab (600 mg). Alemtuzumab data were of pooled treatment-naive patients from the CAMMS223 and CARE-MS I studies (n = 786), and separately, patients with inadequate response to prior therapy from CARE-MS II (n = 628). Ocrelizumab data were derived from the OPERA I and II studies (n = 821 and n = 835, respectively). Alemtuzumab was administered as two annual courses; ocrelizumab was administered at baseline and weeks 24, 48, and 72. Number needed to treat was based on inverse of absolute risk differences versus subcutaneous interferon beta-1a 44 μg three times per week (common comparator) for annualized relapse rate and proportion of patients experiencing relapse, and the Altman method for six-month confirmed disability worsening. Lower number needed to treat values reflect greater efficacy.

Baseline mean Expanded Disability Status Scale (EDSS) scores were 2.0 for CAMMS223 and CARE-MS I, 2.7 for CARE-MS II, 2.9 for OPERA I, and 2.8 for OPERA II. Mean MS duration was 1.9 years in CAMMS223 and CARE-MS I, 4.5 years in CARE-MS II, and 6.7 years in OPERA I and II. Mean number of relapses in the previous two years was 2.5 for CAMMS223 and CARE-MS I, 2.8 for CARE-MS II, and 1.8 in OPERA I and II.

Alemtuzumab and ocrelizumab significantly reduced annualized relapse rates and confirmed disability worsening versus subcutaneous interferon beta-1a. Number needed to treat values to prevent one relapse versus subcutaneous interferon beta-1a were lower with alemtuzumab (CAMMS223/CARE-MS I: five; CARE-MS II: four) than with ocrelizumab (OPERA I/II: eight in each study), as were number needed to treat values to prevent one patient from experiencing relapse (CAMMS223/CARE-MS I and CARE-MS II: six in each study; OPERA I and II: eight in each study), and to prevent one patient from experiencing six-month confirmed disability worsening (CAMMS223/CARE-MS I: 15; CARE-MS II: 13; OPERA I: 23; OPERA II: 21).

Although the populations in the available datasets differ, these findings suggest a benefit of alemtuzumab over ocrelizumab.

This study was supported by Sanofi Genzyme.

A Large Case–Control Analysis

Previous studies have provided evidence for an MS prodrome that occurs years before a demyelinating event or the onset of clinical symptoms. Many of these studies, however, have been limited by a retrospective design or by the absence of a control group.

To analyze the question further, Dr. Tremlett and colleagues examined data from linked health administrative and clinical databases in the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia, which were chosen for their geographic diversity and comprehensive data. The researchers created a health administrative cohort, which was based on administrative data, and an MS clinic-derived cohort, which used administrative and clinical data. The study’s primary outcome was all-cause use of health care during each of the five years before the health administrative index date (ie, the first demyelinating disease-related claim) or clinical index date (ie, the date of MS symptom onset).

Health Care Use Increased in Prodromal MS

The health administrative cohort included 14,428 people with MS and 72,059 matched controls. In all, 10,525 (73%) of the patients with MS were women, and their mean age at the health administrative index date was 43. Compared with controls, annual health care use increased steadily between five years and one year before the first demyelinating disease claim in these patients.

The mean number of hospital admissions was 26% higher in people with MS than in controls in the fifth year before the index date, and 78% higher in the year before the index date. The mean number of physician claims was 24% higher in people with MS than in controls in the fifth year before the index date, and 88% higher in people with MS than in controls in the year before the index date. Also, the mean number of prescribed drug classes was 23% higher in people with MS than in matched controls in the fifth year before the index date, and 49% higher in people with MS than in controls in the year before the index date.

The MS clinic cohort included 3,202 people with MS and 16,006 matched controls. In all, 2,368 (74%) of people with MS were women, and the mean age at the clinical index date was approximately 37. Compared with the health administrative cohort, this cohort had similar patterns for physician claims and prescriptions, although the differences in use in each of the five years mostly did not reach statistical significance.

“To gain a better insight into the MS prodrome, the complex reasons for increased health care use will need to be established, for example, through access of additional administrative data such as the specific diagnostic codes related to a hospital admission or physician visit, or the therapeutic drug class for a prescription,” Dr. Tremlett concluded.

—Erik Greb

Suggested Reading

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017 Apr 20 [Epub ahead of print].

A Large Case–Control Analysis

Previous studies have provided evidence for an MS prodrome that occurs years before a demyelinating event or the onset of clinical symptoms. Many of these studies, however, have been limited by a retrospective design or by the absence of a control group.

To analyze the question further, Dr. Tremlett and colleagues examined data from linked health administrative and clinical databases in the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia, which were chosen for their geographic diversity and comprehensive data. The researchers created a health administrative cohort, which was based on administrative data, and an MS clinic-derived cohort, which used administrative and clinical data. The study’s primary outcome was all-cause use of health care during each of the five years before the health administrative index date (ie, the first demyelinating disease-related claim) or clinical index date (ie, the date of MS symptom onset).

Health Care Use Increased in Prodromal MS

The health administrative cohort included 14,428 people with MS and 72,059 matched controls. In all, 10,525 (73%) of the patients with MS were women, and their mean age at the health administrative index date was 43. Compared with controls, annual health care use increased steadily between five years and one year before the first demyelinating disease claim in these patients.

The mean number of hospital admissions was 26% higher in people with MS than in controls in the fifth year before the index date, and 78% higher in the year before the index date. The mean number of physician claims was 24% higher in people with MS than in controls in the fifth year before the index date, and 88% higher in people with MS than in controls in the year before the index date. Also, the mean number of prescribed drug classes was 23% higher in people with MS than in matched controls in the fifth year before the index date, and 49% higher in people with MS than in controls in the year before the index date.

The MS clinic cohort included 3,202 people with MS and 16,006 matched controls. In all, 2,368 (74%) of people with MS were women, and the mean age at the clinical index date was approximately 37. Compared with the health administrative cohort, this cohort had similar patterns for physician claims and prescriptions, although the differences in use in each of the five years mostly did not reach statistical significance.

“To gain a better insight into the MS prodrome, the complex reasons for increased health care use will need to be established, for example, through access of additional administrative data such as the specific diagnostic codes related to a hospital admission or physician visit, or the therapeutic drug class for a prescription,” Dr. Tremlett concluded.

—Erik Greb

Suggested Reading

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017 Apr 20 [Epub ahead of print].

A Large Case–Control Analysis

Previous studies have provided evidence for an MS prodrome that occurs years before a demyelinating event or the onset of clinical symptoms. Many of these studies, however, have been limited by a retrospective design or by the absence of a control group.

To analyze the question further, Dr. Tremlett and colleagues examined data from linked health administrative and clinical databases in the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia, which were chosen for their geographic diversity and comprehensive data. The researchers created a health administrative cohort, which was based on administrative data, and an MS clinic-derived cohort, which used administrative and clinical data. The study’s primary outcome was all-cause use of health care during each of the five years before the health administrative index date (ie, the first demyelinating disease-related claim) or clinical index date (ie, the date of MS symptom onset).

Health Care Use Increased in Prodromal MS

The health administrative cohort included 14,428 people with MS and 72,059 matched controls. In all, 10,525 (73%) of the patients with MS were women, and their mean age at the health administrative index date was 43. Compared with controls, annual health care use increased steadily between five years and one year before the first demyelinating disease claim in these patients.

The mean number of hospital admissions was 26% higher in people with MS than in controls in the fifth year before the index date, and 78% higher in the year before the index date. The mean number of physician claims was 24% higher in people with MS than in controls in the fifth year before the index date, and 88% higher in people with MS than in controls in the year before the index date. Also, the mean number of prescribed drug classes was 23% higher in people with MS than in matched controls in the fifth year before the index date, and 49% higher in people with MS than in controls in the year before the index date.

The MS clinic cohort included 3,202 people with MS and 16,006 matched controls. In all, 2,368 (74%) of people with MS were women, and the mean age at the clinical index date was approximately 37. Compared with the health administrative cohort, this cohort had similar patterns for physician claims and prescriptions, although the differences in use in each of the five years mostly did not reach statistical significance.

“To gain a better insight into the MS prodrome, the complex reasons for increased health care use will need to be established, for example, through access of additional administrative data such as the specific diagnostic codes related to a hospital admission or physician visit, or the therapeutic drug class for a prescription,” Dr. Tremlett concluded.

—Erik Greb

Suggested Reading

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017 Apr 20 [Epub ahead of print].