ICYMI Multiple Sclerosis

The prevalence of multiple sclerosis (MS) has increased substantially in many regions around the world since 1990, according to The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). These recent findings will be useful for resource allocation and planning in health services. Researchers assessed the epidemiology of MS from 1990 to 2016. Data on prevalence and deaths are summarized in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. They found:

• In 2016, there were 2,221,188 prevalent cases of MS globally, which corresponded to a 10.4% increase in the age-standardized prevalence since 1990.
• The highest age-standardized MS prevalence estimates per 100,000 persons were in high-income North America (164.6), western Europe (127.0), and Australasia (91.1), and the lowest were in eastern sub-Saharan Africa (3.3), central sub-Saharan African (2.8), and Oceania (2.0).
• There were 18,932 deaths due to MS and 1,151,478 DALYs due to MS in 2016.
• Globally, age-standardized death rates decreased significantly (change −11.5%), whereas the change in age-standardized DALYs was not significant (−4.2%,).

GBD 2016 Multiple Sclerosis Collaborators. Global, regional, and national burden of multiple sclerosis 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(3):269-285. doi:10.1016/S1474-4422(18)30443-5.

The prevalence of multiple sclerosis (MS) has increased substantially in many regions around the world since 1990, according to The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). These recent findings will be useful for resource allocation and planning in health services. Researchers assessed the epidemiology of MS from 1990 to 2016. Data on prevalence and deaths are summarized in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. They found:

• In 2016, there were 2,221,188 prevalent cases of MS globally, which corresponded to a 10.4% increase in the age-standardized prevalence since 1990.
• The highest age-standardized MS prevalence estimates per 100,000 persons were in high-income North America (164.6), western Europe (127.0), and Australasia (91.1), and the lowest were in eastern sub-Saharan Africa (3.3), central sub-Saharan African (2.8), and Oceania (2.0).
• There were 18,932 deaths due to MS and 1,151,478 DALYs due to MS in 2016.
• Globally, age-standardized death rates decreased significantly (change −11.5%), whereas the change in age-standardized DALYs was not significant (−4.2%,).

GBD 2016 Multiple Sclerosis Collaborators. Global, regional, and national burden of multiple sclerosis 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(3):269-285. doi:10.1016/S1474-4422(18)30443-5.

The prevalence of multiple sclerosis (MS) has increased substantially in many regions around the world since 1990, according to The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). These recent findings will be useful for resource allocation and planning in health services. Researchers assessed the epidemiology of MS from 1990 to 2016. Data on prevalence and deaths are summarized in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. They found:

• In 2016, there were 2,221,188 prevalent cases of MS globally, which corresponded to a 10.4% increase in the age-standardized prevalence since 1990.
• The highest age-standardized MS prevalence estimates per 100,000 persons were in high-income North America (164.6), western Europe (127.0), and Australasia (91.1), and the lowest were in eastern sub-Saharan Africa (3.3), central sub-Saharan African (2.8), and Oceania (2.0).
• There were 18,932 deaths due to MS and 1,151,478 DALYs due to MS in 2016.
• Globally, age-standardized death rates decreased significantly (change −11.5%), whereas the change in age-standardized DALYs was not significant (−4.2%,).

GBD 2016 Multiple Sclerosis Collaborators. Global, regional, and national burden of multiple sclerosis 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(3):269-285. doi:10.1016/S1474-4422(18)30443-5.

Dr. Joseph Berger’s article The Financial Contribution of the Multiple Sclerosis Specialist
(Neurol Clin Pract. 2017;7:246-255) is an eye-opening examination of how multiple sclerosis (MS) specialists fit into the economic framework of large academic institutions. We sat down with Dr. Berger to discuss his findings.

How would you describe the downstream revenue generated from MS specialists at large academic institutions?

The downstream revenue generated from MS is highly dependent on whether the drugs prescribed to patients are provided by the academic institution, and whether the infusions and imaging studies are done at the academic institution.

Another component is whether that institution operates under a Medicare 340B, a law that enables the institutions that are providing care to the underserved to acquire drugs at a steeply discounted price. And, as cited in the paper, the Office of the Inspector General of the Department of Health and Human Services estimated that the profit margin is 58% for all the drugs being provided under 340B. It’s important to note that that statistic accounts for all drugs, not a specific drug or a specific class of drugs. But, for the sake of argument let’s assume that it’s 50% for MS drugs.

The typical MS drug costs $60,000 a year if not more, and that means that 50% of that total goes to the contribution margin of the MS provider or the MS clinic. If there are 1000 patients for whom the specialty pharmacy within the institution is providing drugs, that means an enormous amount of money is returning to the institution as a result of the contribution by the MS practitioners.

In addition to the cost of the drugs, there’s also the cost of infusions associated with the drug that contributes substantially to the bottom line of the institution.

MS specialists tend to do more imaging studies than any other discipline. At the time of diagnosis, individuals with MS get MRIs of brain, cervical and thoracic spine, and frequently the orbits. The frequency with which these images are repeated depends on the nature of the patient’s illness, the activity of their disease, etc.

How do you make a case to administrators for more funding in MS centers?

Unfortunately, the downstream revenue does not always find its way back to the MS centers. Moreover, MS practitioners are forced to prove their value to the institution before they can receive the resources that they need.

There are only two things that administrators in medical institutions respond to. The first is need. The second is the financial impact of the activity.

Here is an example from my own personal experience. I prescribed a specific drug for a patient who did not live close to the institution. It took three months for the patient to receive the drug. This was due, in large measure, to problems with the insurance company and the outside specialty pharmacies that we were dealing with. In that course of time the patient suffered two relapses from which she never fully recovered.

I thought we could do a much better job treating our patients if our own specialty pharmacy was providing the drug. Eventually, after some negotiating with the administration, we were able to provide all those drugs through our specialty pharmacy. That change resulted in a significant increase in terms of contribution margin for the MS team, and it was a great benefit for our patients.

How does MS compare with other neurology disciplines?

If you look at the contribution margin from MS and compare it to in any other division in neurology, it exceeds all of them combined by a significant percentage.

For example, the current contribution margin in the MS division at the University of Pennsylvania exceeds that of virtually any other line within the Neuroscience Center Service, which includes neurosurgery. It is on par with, and may exceed, that of spine surgery, which in the past had always been the biggest driver of the contribution margin from the Neuroscience service line.

Often, MS specialists aren’t getting the resources needed despite the fact that their growing practice would enhance the contribution margin.

Since this has been brought to the attention of the administration at the University of Pennsylvania, there have been increased resources available for the division; we now have more nurses and nurse practitioners, and we have pharmacists within the division. All of this has made a big difference in helping to provide the best care for our patients.

How would you characterize the compensation of the MS specialist?

One of the things that I did address in the article, but only obliquely, is the compensation of the MS neurologist.

Historically, the MS neurologist was among the least compensated of all the neurology disciplines, in academics as well as in private practice. The reason for this was simple. Until the early 1990s, there were very few drugs to treat MS. It was more a matter of diagnosing people and treating the symptoms as they arose. When drugs for MS emerged, they were not particularly complex to manage.

However, as new drugs have become available, and the efficacy of these drugs increased, so did their side effect profiles. A need arose for specialists to manage the treatment of patients with MS.

I hope to address this further in a future publication, but the underlying assertion is that the compensation of the MS neurologist needs to be revisited at both academic institutions and in the community.

Final thoughts?

The article was an attempt to educate not just the MS community, but the broader neurologic community as to the value of an MS specialist to an institution.

The purpose of this article was to encourage people to think about their worth and the worth of what they do as it applies to the financial well-being of the institution with which they’re associated.

Dr. Joseph Berger’s article The Financial Contribution of the Multiple Sclerosis Specialist
(Neurol Clin Pract. 2017;7:246-255) is an eye-opening examination of how multiple sclerosis (MS) specialists fit into the economic framework of large academic institutions. We sat down with Dr. Berger to discuss his findings.

How would you describe the downstream revenue generated from MS specialists at large academic institutions?

The downstream revenue generated from MS is highly dependent on whether the drugs prescribed to patients are provided by the academic institution, and whether the infusions and imaging studies are done at the academic institution.

Another component is whether that institution operates under a Medicare 340B, a law that enables the institutions that are providing care to the underserved to acquire drugs at a steeply discounted price. And, as cited in the paper, the Office of the Inspector General of the Department of Health and Human Services estimated that the profit margin is 58% for all the drugs being provided under 340B. It’s important to note that that statistic accounts for all drugs, not a specific drug or a specific class of drugs. But, for the sake of argument let’s assume that it’s 50% for MS drugs.

The typical MS drug costs $60,000 a year if not more, and that means that 50% of that total goes to the contribution margin of the MS provider or the MS clinic. If there are 1000 patients for whom the specialty pharmacy within the institution is providing drugs, that means an enormous amount of money is returning to the institution as a result of the contribution by the MS practitioners.

In addition to the cost of the drugs, there’s also the cost of infusions associated with the drug that contributes substantially to the bottom line of the institution.

MS specialists tend to do more imaging studies than any other discipline. At the time of diagnosis, individuals with MS get MRIs of brain, cervical and thoracic spine, and frequently the orbits. The frequency with which these images are repeated depends on the nature of the patient’s illness, the activity of their disease, etc.

How do you make a case to administrators for more funding in MS centers?

Unfortunately, the downstream revenue does not always find its way back to the MS centers. Moreover, MS practitioners are forced to prove their value to the institution before they can receive the resources that they need.

There are only two things that administrators in medical institutions respond to. The first is need. The second is the financial impact of the activity.

Here is an example from my own personal experience. I prescribed a specific drug for a patient who did not live close to the institution. It took three months for the patient to receive the drug. This was due, in large measure, to problems with the insurance company and the outside specialty pharmacies that we were dealing with. In that course of time the patient suffered two relapses from which she never fully recovered.

I thought we could do a much better job treating our patients if our own specialty pharmacy was providing the drug. Eventually, after some negotiating with the administration, we were able to provide all those drugs through our specialty pharmacy. That change resulted in a significant increase in terms of contribution margin for the MS team, and it was a great benefit for our patients.

How does MS compare with other neurology disciplines?

If you look at the contribution margin from MS and compare it to in any other division in neurology, it exceeds all of them combined by a significant percentage.

For example, the current contribution margin in the MS division at the University of Pennsylvania exceeds that of virtually any other line within the Neuroscience Center Service, which includes neurosurgery. It is on par with, and may exceed, that of spine surgery, which in the past had always been the biggest driver of the contribution margin from the Neuroscience service line.

Often, MS specialists aren’t getting the resources needed despite the fact that their growing practice would enhance the contribution margin.

Since this has been brought to the attention of the administration at the University of Pennsylvania, there have been increased resources available for the division; we now have more nurses and nurse practitioners, and we have pharmacists within the division. All of this has made a big difference in helping to provide the best care for our patients.

How would you characterize the compensation of the MS specialist?

One of the things that I did address in the article, but only obliquely, is the compensation of the MS neurologist.

Historically, the MS neurologist was among the least compensated of all the neurology disciplines, in academics as well as in private practice. The reason for this was simple. Until the early 1990s, there were very few drugs to treat MS. It was more a matter of diagnosing people and treating the symptoms as they arose. When drugs for MS emerged, they were not particularly complex to manage.

However, as new drugs have become available, and the efficacy of these drugs increased, so did their side effect profiles. A need arose for specialists to manage the treatment of patients with MS.

I hope to address this further in a future publication, but the underlying assertion is that the compensation of the MS neurologist needs to be revisited at both academic institutions and in the community.

Final thoughts?

The article was an attempt to educate not just the MS community, but the broader neurologic community as to the value of an MS specialist to an institution.

The purpose of this article was to encourage people to think about their worth and the worth of what they do as it applies to the financial well-being of the institution with which they’re associated.

Dr. Joseph Berger’s article The Financial Contribution of the Multiple Sclerosis Specialist
(Neurol Clin Pract. 2017;7:246-255) is an eye-opening examination of how multiple sclerosis (MS) specialists fit into the economic framework of large academic institutions. We sat down with Dr. Berger to discuss his findings.

How would you describe the downstream revenue generated from MS specialists at large academic institutions?

The downstream revenue generated from MS is highly dependent on whether the drugs prescribed to patients are provided by the academic institution, and whether the infusions and imaging studies are done at the academic institution.

Another component is whether that institution operates under a Medicare 340B, a law that enables the institutions that are providing care to the underserved to acquire drugs at a steeply discounted price. And, as cited in the paper, the Office of the Inspector General of the Department of Health and Human Services estimated that the profit margin is 58% for all the drugs being provided under 340B. It’s important to note that that statistic accounts for all drugs, not a specific drug or a specific class of drugs. But, for the sake of argument let’s assume that it’s 50% for MS drugs.

The typical MS drug costs $60,000 a year if not more, and that means that 50% of that total goes to the contribution margin of the MS provider or the MS clinic. If there are 1000 patients for whom the specialty pharmacy within the institution is providing drugs, that means an enormous amount of money is returning to the institution as a result of the contribution by the MS practitioners.

In addition to the cost of the drugs, there’s also the cost of infusions associated with the drug that contributes substantially to the bottom line of the institution.

MS specialists tend to do more imaging studies than any other discipline. At the time of diagnosis, individuals with MS get MRIs of brain, cervical and thoracic spine, and frequently the orbits. The frequency with which these images are repeated depends on the nature of the patient’s illness, the activity of their disease, etc.

How do you make a case to administrators for more funding in MS centers?

Unfortunately, the downstream revenue does not always find its way back to the MS centers. Moreover, MS practitioners are forced to prove their value to the institution before they can receive the resources that they need.

There are only two things that administrators in medical institutions respond to. The first is need. The second is the financial impact of the activity.

Here is an example from my own personal experience. I prescribed a specific drug for a patient who did not live close to the institution. It took three months for the patient to receive the drug. This was due, in large measure, to problems with the insurance company and the outside specialty pharmacies that we were dealing with. In that course of time the patient suffered two relapses from which she never fully recovered.

I thought we could do a much better job treating our patients if our own specialty pharmacy was providing the drug. Eventually, after some negotiating with the administration, we were able to provide all those drugs through our specialty pharmacy. That change resulted in a significant increase in terms of contribution margin for the MS team, and it was a great benefit for our patients.

How does MS compare with other neurology disciplines?

If you look at the contribution margin from MS and compare it to in any other division in neurology, it exceeds all of them combined by a significant percentage.

For example, the current contribution margin in the MS division at the University of Pennsylvania exceeds that of virtually any other line within the Neuroscience Center Service, which includes neurosurgery. It is on par with, and may exceed, that of spine surgery, which in the past had always been the biggest driver of the contribution margin from the Neuroscience service line.

Often, MS specialists aren’t getting the resources needed despite the fact that their growing practice would enhance the contribution margin.

Since this has been brought to the attention of the administration at the University of Pennsylvania, there have been increased resources available for the division; we now have more nurses and nurse practitioners, and we have pharmacists within the division. All of this has made a big difference in helping to provide the best care for our patients.

How would you characterize the compensation of the MS specialist?

One of the things that I did address in the article, but only obliquely, is the compensation of the MS neurologist.

Historically, the MS neurologist was among the least compensated of all the neurology disciplines, in academics as well as in private practice. The reason for this was simple. Until the early 1990s, there were very few drugs to treat MS. It was more a matter of diagnosing people and treating the symptoms as they arose. When drugs for MS emerged, they were not particularly complex to manage.

However, as new drugs have become available, and the efficacy of these drugs increased, so did their side effect profiles. A need arose for specialists to manage the treatment of patients with MS.

I hope to address this further in a future publication, but the underlying assertion is that the compensation of the MS neurologist needs to be revisited at both academic institutions and in the community.

Final thoughts?

The article was an attempt to educate not just the MS community, but the broader neurologic community as to the value of an MS specialist to an institution.

The purpose of this article was to encourage people to think about their worth and the worth of what they do as it applies to the financial well-being of the institution with which they’re associated.

Contrary to recent reports, resting core temperature is not elevated in patients with relapsing-remitting multiple sclerosis (RRMS) compared to healthy controls when measured using precision thermometry, according to a recent study. Furthermore, no association was observed between resting rectal temperature (T_re) and any subjective measures of fatigue in a subset of participants with MS. Across 2 international data collection sites (Sydney and Dallas), 28 RRMS patients and 27 aged-matched controls (CON) were exposed to either 30°C, 30% relative humidity (RH) (Sydney) or 25°C, 30% RH (Dallas). Resting T_re and esophageal (T_eso) temperature and resting oxygen consumption (VO₂) was measured in MS (n=28) and CON (n=27) groups who completed the 25°C and 30°C trials. Tympanic membrane (T_tym) temperature was measured in MS (n=16) and CON (n=15) groups in the 30°C condition. A modified fatigue impact scale (MFIS) questionnaire was used to assess subjective measures of psychosocial, physical, and cognitive fatigue in the 30°C condition. Researchers found:

• Irrespective of ambient temperature, no group differences were observed for T_re, T_eso, or resting VO₂.
• Similarly, no group differences were observed for T_tym in the 30°C condition.

Chaseling GK, Allen DR, Vucic S, et al. Core temperature is not elevated at rest in people with relapsing-remitting multiple sclerosis. [Published online ahead of print January 3, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.01.013.

Contrary to recent reports, resting core temperature is not elevated in patients with relapsing-remitting multiple sclerosis (RRMS) compared to healthy controls when measured using precision thermometry, according to a recent study. Furthermore, no association was observed between resting rectal temperature (T_re) and any subjective measures of fatigue in a subset of participants with MS. Across 2 international data collection sites (Sydney and Dallas), 28 RRMS patients and 27 aged-matched controls (CON) were exposed to either 30°C, 30% relative humidity (RH) (Sydney) or 25°C, 30% RH (Dallas). Resting T_re and esophageal (T_eso) temperature and resting oxygen consumption (VO₂) was measured in MS (n=28) and CON (n=27) groups who completed the 25°C and 30°C trials. Tympanic membrane (T_tym) temperature was measured in MS (n=16) and CON (n=15) groups in the 30°C condition. A modified fatigue impact scale (MFIS) questionnaire was used to assess subjective measures of psychosocial, physical, and cognitive fatigue in the 30°C condition. Researchers found:

• Irrespective of ambient temperature, no group differences were observed for T_re, T_eso, or resting VO₂.
• Similarly, no group differences were observed for T_tym in the 30°C condition.

Chaseling GK, Allen DR, Vucic S, et al. Core temperature is not elevated at rest in people with relapsing-remitting multiple sclerosis. [Published online ahead of print January 3, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.01.013.

Contrary to recent reports, resting core temperature is not elevated in patients with relapsing-remitting multiple sclerosis (RRMS) compared to healthy controls when measured using precision thermometry, according to a recent study. Furthermore, no association was observed between resting rectal temperature (T_re) and any subjective measures of fatigue in a subset of participants with MS. Across 2 international data collection sites (Sydney and Dallas), 28 RRMS patients and 27 aged-matched controls (CON) were exposed to either 30°C, 30% relative humidity (RH) (Sydney) or 25°C, 30% RH (Dallas). Resting T_re and esophageal (T_eso) temperature and resting oxygen consumption (VO₂) was measured in MS (n=28) and CON (n=27) groups who completed the 25°C and 30°C trials. Tympanic membrane (T_tym) temperature was measured in MS (n=16) and CON (n=15) groups in the 30°C condition. A modified fatigue impact scale (MFIS) questionnaire was used to assess subjective measures of psychosocial, physical, and cognitive fatigue in the 30°C condition. Researchers found:

• Irrespective of ambient temperature, no group differences were observed for T_re, T_eso, or resting VO₂.
• Similarly, no group differences were observed for T_tym in the 30°C condition.

Chaseling GK, Allen DR, Vucic S, et al. Core temperature is not elevated at rest in people with relapsing-remitting multiple sclerosis. [Published online ahead of print January 3, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.01.013.

Persons with multiple sclerosis (MS) who have greater disability exhibit higher body fat and lower bone tissue content and density than those with mild disability, a recent study found. Researchers conducted a cross-sectional investigation of 47 ambulatory persons with relapsing remitting MS who were grouped by Expanded Disability Status Scale (EDSS) scores as having mild (1.0‒4.0; n=26) or moderate (4.5‒6.5; n=21) disability. Main outcome measures were whole-body and regional soft tissue composition (%body fat [BF], fat mass [FM], and fat-free soft tissue mass [FFM]), bone mineral content (BMC), and bone mineral density (BMD). Other outcomes included physical fitness, mobility, cognitive processing speed, symptoms, and health-related quality of life (HRQOL). They found:

• Whole-body and regional %BF and FM were significantly higher, and whole-body and appendicular BMC and BMD were significantly lower in participants with moderate disability than those with mild disability.
• There were no significant differences in whole-body or regional FFM by disability status.
• In the overall sample, body fat correlated significantly with cardiorespiratory fitness, pain symptoms, and psychological HRQOL.
• FFM and BMC correlated primarily with measures of muscular strength.

Pilutti LA, Motl RW. Body composition and disability in people with multiple sclerosis: A dual-energy x-ray absorptiometry study. [Published online ahead of print January 3, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.01.009.

Persons with multiple sclerosis (MS) who have greater disability exhibit higher body fat and lower bone tissue content and density than those with mild disability, a recent study found. Researchers conducted a cross-sectional investigation of 47 ambulatory persons with relapsing remitting MS who were grouped by Expanded Disability Status Scale (EDSS) scores as having mild (1.0‒4.0; n=26) or moderate (4.5‒6.5; n=21) disability. Main outcome measures were whole-body and regional soft tissue composition (%body fat [BF], fat mass [FM], and fat-free soft tissue mass [FFM]), bone mineral content (BMC), and bone mineral density (BMD). Other outcomes included physical fitness, mobility, cognitive processing speed, symptoms, and health-related quality of life (HRQOL). They found:

• Whole-body and regional %BF and FM were significantly higher, and whole-body and appendicular BMC and BMD were significantly lower in participants with moderate disability than those with mild disability.
• There were no significant differences in whole-body or regional FFM by disability status.
• In the overall sample, body fat correlated significantly with cardiorespiratory fitness, pain symptoms, and psychological HRQOL.
• FFM and BMC correlated primarily with measures of muscular strength.

Pilutti LA, Motl RW. Body composition and disability in people with multiple sclerosis: A dual-energy x-ray absorptiometry study. [Published online ahead of print January 3, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.01.009.

Persons with multiple sclerosis (MS) who have greater disability exhibit higher body fat and lower bone tissue content and density than those with mild disability, a recent study found. Researchers conducted a cross-sectional investigation of 47 ambulatory persons with relapsing remitting MS who were grouped by Expanded Disability Status Scale (EDSS) scores as having mild (1.0‒4.0; n=26) or moderate (4.5‒6.5; n=21) disability. Main outcome measures were whole-body and regional soft tissue composition (%body fat [BF], fat mass [FM], and fat-free soft tissue mass [FFM]), bone mineral content (BMC), and bone mineral density (BMD). Other outcomes included physical fitness, mobility, cognitive processing speed, symptoms, and health-related quality of life (HRQOL). They found:

• Whole-body and regional %BF and FM were significantly higher, and whole-body and appendicular BMC and BMD were significantly lower in participants with moderate disability than those with mild disability.
• There were no significant differences in whole-body or regional FFM by disability status.
• In the overall sample, body fat correlated significantly with cardiorespiratory fitness, pain symptoms, and psychological HRQOL.
• FFM and BMC correlated primarily with measures of muscular strength.

Pilutti LA, Motl RW. Body composition and disability in people with multiple sclerosis: A dual-energy x-ray absorptiometry study. [Published online ahead of print January 3, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.01.009.

The prevalence of pseudobulbar affect (PBA) in multiple sclerosis (MS) is low, according to a recent study, but similar symptoms may co-occur or overlap with depression, highlighting the importance of concomitant assessment of mood when evaluating potential PBA. Furthermore, PBA may be associated with cognitive impairment in people with MS. North American Research Committee on MS (NARCOMS) registry participants completed the Center for Neurologic Study-Lability Scale (CNS-LS), a validated 7-question self-report measure of PBA. Researchers categorized individuals as PBA-positive (PBA[+]) if they had a composite score ≥17 without current depression. Participants also reported their demographic characteristics and their clinical characteristics using Patient-Determined Disease Steps and Performance Scales. They found:

• Of the 8,136 responders, 574 (7%) had scores ≥17 on the CNS-LS; however, only 200 (2.5%) individuals had scores ≥17 without comorbid depression, of whom only 22 (11%) reported a diagnosis of PBA.
• PBA(+) individuals tended to be younger (mean [SD] 53.4 [11.0] vs 57.2 [10.3] years), non-white (13% vs 9%), and have lower socioeconomic status (≤$30,000 annual income: 28% vs 22%).
• In multivariable models, PBA(+) was associated with increased odds of more severe cognitive impairment.

Fitzgerald KC, Salter A, Tyry T, Fox RJ, Cutter G, Marrie RA. Pseudobulbar affect.

Prevalence and association with symptoms in multiple sclerosis. Neurol Clin Pract. 2018;8(6):472-481. doi:10.1212/CPJ.0000000000000523.

The prevalence of pseudobulbar affect (PBA) in multiple sclerosis (MS) is low, according to a recent study, but similar symptoms may co-occur or overlap with depression, highlighting the importance of concomitant assessment of mood when evaluating potential PBA. Furthermore, PBA may be associated with cognitive impairment in people with MS. North American Research Committee on MS (NARCOMS) registry participants completed the Center for Neurologic Study-Lability Scale (CNS-LS), a validated 7-question self-report measure of PBA. Researchers categorized individuals as PBA-positive (PBA[+]) if they had a composite score ≥17 without current depression. Participants also reported their demographic characteristics and their clinical characteristics using Patient-Determined Disease Steps and Performance Scales. They found:

• Of the 8,136 responders, 574 (7%) had scores ≥17 on the CNS-LS; however, only 200 (2.5%) individuals had scores ≥17 without comorbid depression, of whom only 22 (11%) reported a diagnosis of PBA.
• PBA(+) individuals tended to be younger (mean [SD] 53.4 [11.0] vs 57.2 [10.3] years), non-white (13% vs 9%), and have lower socioeconomic status (≤$30,000 annual income: 28% vs 22%).
• In multivariable models, PBA(+) was associated with increased odds of more severe cognitive impairment.

Fitzgerald KC, Salter A, Tyry T, Fox RJ, Cutter G, Marrie RA. Pseudobulbar affect.

Prevalence and association with symptoms in multiple sclerosis. Neurol Clin Pract. 2018;8(6):472-481. doi:10.1212/CPJ.0000000000000523.

The prevalence of pseudobulbar affect (PBA) in multiple sclerosis (MS) is low, according to a recent study, but similar symptoms may co-occur or overlap with depression, highlighting the importance of concomitant assessment of mood when evaluating potential PBA. Furthermore, PBA may be associated with cognitive impairment in people with MS. North American Research Committee on MS (NARCOMS) registry participants completed the Center for Neurologic Study-Lability Scale (CNS-LS), a validated 7-question self-report measure of PBA. Researchers categorized individuals as PBA-positive (PBA[+]) if they had a composite score ≥17 without current depression. Participants also reported their demographic characteristics and their clinical characteristics using Patient-Determined Disease Steps and Performance Scales. They found:

• Of the 8,136 responders, 574 (7%) had scores ≥17 on the CNS-LS; however, only 200 (2.5%) individuals had scores ≥17 without comorbid depression, of whom only 22 (11%) reported a diagnosis of PBA.
• PBA(+) individuals tended to be younger (mean [SD] 53.4 [11.0] vs 57.2 [10.3] years), non-white (13% vs 9%), and have lower socioeconomic status (≤$30,000 annual income: 28% vs 22%).
• In multivariable models, PBA(+) was associated with increased odds of more severe cognitive impairment.

Fitzgerald KC, Salter A, Tyry T, Fox RJ, Cutter G, Marrie RA. Pseudobulbar affect.

Prevalence and association with symptoms in multiple sclerosis. Neurol Clin Pract. 2018;8(6):472-481. doi:10.1212/CPJ.0000000000000523.

Disease-modifying therapies give patients with relapsing-remitting multiple sclerosis a lower risk of developing secondary progressive disease that may only be topped in specific patients with highly active disease by the use of nonmyeloablative hematopoietic stem cell transplantation, according to findings from two studies published online Jan. 15 in JAMA.

copyright Zerbor/Thinkstock

The first study found that interferon-beta, glatiramer acetate (Copaxone), fingolimod (Gilenya), natalizumab (Tysabri), and alemtuzumab (Lemtrada) are associated with a lower risk of conversion to secondary progressive MS, compared with no treatment. Initial treatment with the newer therapies provided a greater risk reduction, compared with initial treatment with interferon-beta or glatiramer acetate.

The second study, described as “the first randomized trial of HSCT [nonmyeloablative hematopoietic stem cell transplantation] in patients with relapsing-remitting MS,” suggests that HSCT prolongs the time to disease progression, compared with disease-modifying therapies (DMTs). It also suggests that HSCT can lead to clinical improvement.
 

DMTs reduced risk of conversion to secondary progressive MS

Few previous studies have examined the association between DMTs and the risk of conversion from relapsing-remitting MS to secondary progressive MS. Those that have analyzed this association have not used a validated definition of secondary progressive MS. J. William L. Brown, MD, of the University of Cambridge, England, and his colleagues used a validated definition of secondary progressive MS that was published in 2016 to investigate how DMTs affect the rate of conversion, compared with no treatment. The researchers also compared the risk reduction provided by fingolimod, alemtuzumab, or natalizumab with that provided by interferon-beta or glatiramer acetate.

Dr. Brown and his colleagues analyzed prospectively collected clinical data from an international observational cohort study called MSBase. Eligible participants had relapsing-remitting MS, the complete MSBase minimum data set, at least one Expanded Disability Status Scale (EDSS) score recorded within 6 months before baseline, and at least two EDSS scores recorded after baseline. Participants initiated a DMT or began clinical monitoring during 1988-2012. The population had a minimum follow-up duration of 4 years. Patients who stopped their initial therapy within 6 months and those participating in clinical trials were excluded.

The primary outcome was conversion to secondary progressive MS. Dr. Brown and his colleagues defined this outcome as an EDSS increase of 1 point for participants with a baseline EDSS score of 5.5 or less and as an increase of 0.5 points for participants with a baseline EDSS score higher than 5.5. This increase had to occur in the absence of relapses and be confirmed at a subsequent visit 3 or fewer months later. In addition, the increased EDSS score had to be 4 or more.

After excluding ineligible participants, the investigators matched 1,555 patients from 68 centers in 21 countries. Each therapy analyzed was associated with reduced risk of converting to secondary progressive MS, compared with no treatment. The hazard ratios for conversion were 0.71 for interferon-beta or glatiramer acetate, 0.37 for fingolimod, 0.61 for natalizumab, and 0.52 for alemtuzumab, compared with no treatment.

Treatment with interferon-beta or glatiramer acetate within 5 years of disease onset was associated with a reduced risk of conversion (HR, 0.77), compared with treatment later than 5 years after disease onset. Similarly, patients who escalated treatment from interferon-beta or glatiramer acetate to any of the other three DMTs within 5 years of disease onset had a significantly lower risk of conversion (HR, 0.76) than did those who escalated later. Furthermore, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly reduced risk of conversion (HR, 0.66), compared with initial treatment with interferon-beta or glatiramer acetate.

One of the study’s limitations is its observational design, which precludes the determination of causality, Dr. Brown and his colleagues said. In addition, functional score subcomponents of the EDSS were unavailable, which prevented the researchers from using the definition of secondary progressive MS with the best combination of sensitivity, specificity, and accuracy. Some analyses were limited by small numbers of patients, and the study did not evaluate the risks associated with DMTs. Nevertheless, “these findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

Financial support for this study was provided by the National Health and Medical Research Council of Australia and the University of Melbourne. Dr. Brown received a Next Generation Fellowship funded by the Grand Charity of the Freemasons and an MSBase 2017 Fellowship. Alemtuzumab studies conducted in Cambridge were supported by the National Institute for Health Research Cambridge Biomedical Research Centre and the MS Society UK.
 

HSCT delayed disease progression

In a previous case series, Richard K. Burt, MD, of Northwestern University in Chicago, and his colleagues found that patients with relapsing-remitting MS who underwent nonmyeloablative HSCT had neurologic improvement and a 70% likelihood of having a 4-year period of disease remission. Dr. Burt and his colleagues undertook the MS international stem cell transplant trial to compare the effects of nonmyeloablative HSCT with those of continued DMT treatment on disease progression in participants with highly active relapsing-remitting MS.

The researchers enrolled 110 participants at four international centers into their open-label trial. Eligible participants had two or more clinical relapses or one relapse and at least one gadolinium-enhancing lesion at a separate time within the previous 12 months, despite DMT treatment. The investigators also required participants to have an EDSS score between 2.0 and 6.0. Patients with primary or secondary progressive MS were excluded.

Dr. Burt and his colleagues randomized participants to receive HSCT or an approved DMT that was more effective or in a different class than the one they were receiving at baseline. Ocrelizumab (Ocrevus) was not administered during the study because it had not yet been approved. The investigators excluded alemtuzumab because of its association with persistent lymphopenia and autoimmune disorders. After 1 year of treatment, patients receiving a DMT who had disability progression could cross over to the HSCT arm. Patients randomized to HSCT stopped taking their usual DMT.

Time to disease progression was the study’s primary endpoint. The investigators defined disease progression as an increase in EDSS score of at least 1 point on two evaluations 6 months apart after at least 1 year of treatment. The increase was required to result from MS. The neurologist who recorded participants’ EDSS evaluations was blinded to treatment group assignment.

The researchers randomized 55 patients to each study arm. Approximately 66% of participants were women, and the sample’s mean age was 36 years. There were no significant baseline differences between groups on demographic, clinical, or imaging characteristics. Three patients in the HSCT group were withdrawn from the study, and four in the DMT group were lost to follow-up after seeking HSCT at outside facilities.

Three patients in the HSCT group and 34 patients in the DMT group had disease progression. Mean follow-up duration was 2.8 years. The investigators could not calculate the median time to progression in the HSCT group because too few events occurred. Median time to progression was 24 months in the DMT group (HR, 0.07). During the first year, mean EDSS scores decreased (indicating improvement) from 3.38 to 2.36 in the HSCT group. Mean EDSS scores increased from 3.31 to 3.98 in the DMT group. No participants died, and no patients who received HSCT-developed nonhematopoietic grade 4 toxicities.

“To our knowledge, this is the first randomized trial of HSCT in patients with relapsing-remitting MS,” Dr. Burt and his colleagues said. Although observational studies have found similar EDSS improvements following HSCT, “this degree of improvement has not been demonstrated in pharmaceutical trials even with more intensive DMT such as alemtuzumab,” they concluded.

The Danhakl Family Foundation, the Cumming Foundation, the McNamara Purcell Foundation, Morgan Stanley, and the National Institute for Health Research Sheffield Clinical Research Facility provided financial support for this study. No pharmaceutical companies supported the study.

egreb@mdedge.com

SOURCEs: Brown JWL et al. JAMA. 2019;321(2):175-87. doi: 10.1001/jama.2018.20588.; and Burt RK et al. JAMA. 2019;321(2):165-74. doi: 10.1001/jama.2018.18743.

Disease-modifying therapies give patients with relapsing-remitting multiple sclerosis a lower risk of developing secondary progressive disease that may only be topped in specific patients with highly active disease by the use of nonmyeloablative hematopoietic stem cell transplantation, according to findings from two studies published online Jan. 15 in JAMA.

copyright Zerbor/Thinkstock

The first study found that interferon-beta, glatiramer acetate (Copaxone), fingolimod (Gilenya), natalizumab (Tysabri), and alemtuzumab (Lemtrada) are associated with a lower risk of conversion to secondary progressive MS, compared with no treatment. Initial treatment with the newer therapies provided a greater risk reduction, compared with initial treatment with interferon-beta or glatiramer acetate.

The second study, described as “the first randomized trial of HSCT [nonmyeloablative hematopoietic stem cell transplantation] in patients with relapsing-remitting MS,” suggests that HSCT prolongs the time to disease progression, compared with disease-modifying therapies (DMTs). It also suggests that HSCT can lead to clinical improvement.
 

DMTs reduced risk of conversion to secondary progressive MS

Few previous studies have examined the association between DMTs and the risk of conversion from relapsing-remitting MS to secondary progressive MS. Those that have analyzed this association have not used a validated definition of secondary progressive MS. J. William L. Brown, MD, of the University of Cambridge, England, and his colleagues used a validated definition of secondary progressive MS that was published in 2016 to investigate how DMTs affect the rate of conversion, compared with no treatment. The researchers also compared the risk reduction provided by fingolimod, alemtuzumab, or natalizumab with that provided by interferon-beta or glatiramer acetate.

Dr. Brown and his colleagues analyzed prospectively collected clinical data from an international observational cohort study called MSBase. Eligible participants had relapsing-remitting MS, the complete MSBase minimum data set, at least one Expanded Disability Status Scale (EDSS) score recorded within 6 months before baseline, and at least two EDSS scores recorded after baseline. Participants initiated a DMT or began clinical monitoring during 1988-2012. The population had a minimum follow-up duration of 4 years. Patients who stopped their initial therapy within 6 months and those participating in clinical trials were excluded.

The primary outcome was conversion to secondary progressive MS. Dr. Brown and his colleagues defined this outcome as an EDSS increase of 1 point for participants with a baseline EDSS score of 5.5 or less and as an increase of 0.5 points for participants with a baseline EDSS score higher than 5.5. This increase had to occur in the absence of relapses and be confirmed at a subsequent visit 3 or fewer months later. In addition, the increased EDSS score had to be 4 or more.

After excluding ineligible participants, the investigators matched 1,555 patients from 68 centers in 21 countries. Each therapy analyzed was associated with reduced risk of converting to secondary progressive MS, compared with no treatment. The hazard ratios for conversion were 0.71 for interferon-beta or glatiramer acetate, 0.37 for fingolimod, 0.61 for natalizumab, and 0.52 for alemtuzumab, compared with no treatment.

Treatment with interferon-beta or glatiramer acetate within 5 years of disease onset was associated with a reduced risk of conversion (HR, 0.77), compared with treatment later than 5 years after disease onset. Similarly, patients who escalated treatment from interferon-beta or glatiramer acetate to any of the other three DMTs within 5 years of disease onset had a significantly lower risk of conversion (HR, 0.76) than did those who escalated later. Furthermore, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly reduced risk of conversion (HR, 0.66), compared with initial treatment with interferon-beta or glatiramer acetate.

One of the study’s limitations is its observational design, which precludes the determination of causality, Dr. Brown and his colleagues said. In addition, functional score subcomponents of the EDSS were unavailable, which prevented the researchers from using the definition of secondary progressive MS with the best combination of sensitivity, specificity, and accuracy. Some analyses were limited by small numbers of patients, and the study did not evaluate the risks associated with DMTs. Nevertheless, “these findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

Financial support for this study was provided by the National Health and Medical Research Council of Australia and the University of Melbourne. Dr. Brown received a Next Generation Fellowship funded by the Grand Charity of the Freemasons and an MSBase 2017 Fellowship. Alemtuzumab studies conducted in Cambridge were supported by the National Institute for Health Research Cambridge Biomedical Research Centre and the MS Society UK.
 

HSCT delayed disease progression

In a previous case series, Richard K. Burt, MD, of Northwestern University in Chicago, and his colleagues found that patients with relapsing-remitting MS who underwent nonmyeloablative HSCT had neurologic improvement and a 70% likelihood of having a 4-year period of disease remission. Dr. Burt and his colleagues undertook the MS international stem cell transplant trial to compare the effects of nonmyeloablative HSCT with those of continued DMT treatment on disease progression in participants with highly active relapsing-remitting MS.

The researchers enrolled 110 participants at four international centers into their open-label trial. Eligible participants had two or more clinical relapses or one relapse and at least one gadolinium-enhancing lesion at a separate time within the previous 12 months, despite DMT treatment. The investigators also required participants to have an EDSS score between 2.0 and 6.0. Patients with primary or secondary progressive MS were excluded.

Dr. Burt and his colleagues randomized participants to receive HSCT or an approved DMT that was more effective or in a different class than the one they were receiving at baseline. Ocrelizumab (Ocrevus) was not administered during the study because it had not yet been approved. The investigators excluded alemtuzumab because of its association with persistent lymphopenia and autoimmune disorders. After 1 year of treatment, patients receiving a DMT who had disability progression could cross over to the HSCT arm. Patients randomized to HSCT stopped taking their usual DMT.

Time to disease progression was the study’s primary endpoint. The investigators defined disease progression as an increase in EDSS score of at least 1 point on two evaluations 6 months apart after at least 1 year of treatment. The increase was required to result from MS. The neurologist who recorded participants’ EDSS evaluations was blinded to treatment group assignment.

The researchers randomized 55 patients to each study arm. Approximately 66% of participants were women, and the sample’s mean age was 36 years. There were no significant baseline differences between groups on demographic, clinical, or imaging characteristics. Three patients in the HSCT group were withdrawn from the study, and four in the DMT group were lost to follow-up after seeking HSCT at outside facilities.

Three patients in the HSCT group and 34 patients in the DMT group had disease progression. Mean follow-up duration was 2.8 years. The investigators could not calculate the median time to progression in the HSCT group because too few events occurred. Median time to progression was 24 months in the DMT group (HR, 0.07). During the first year, mean EDSS scores decreased (indicating improvement) from 3.38 to 2.36 in the HSCT group. Mean EDSS scores increased from 3.31 to 3.98 in the DMT group. No participants died, and no patients who received HSCT-developed nonhematopoietic grade 4 toxicities.

“To our knowledge, this is the first randomized trial of HSCT in patients with relapsing-remitting MS,” Dr. Burt and his colleagues said. Although observational studies have found similar EDSS improvements following HSCT, “this degree of improvement has not been demonstrated in pharmaceutical trials even with more intensive DMT such as alemtuzumab,” they concluded.

The Danhakl Family Foundation, the Cumming Foundation, the McNamara Purcell Foundation, Morgan Stanley, and the National Institute for Health Research Sheffield Clinical Research Facility provided financial support for this study. No pharmaceutical companies supported the study.

egreb@mdedge.com

SOURCEs: Brown JWL et al. JAMA. 2019;321(2):175-87. doi: 10.1001/jama.2018.20588.; and Burt RK et al. JAMA. 2019;321(2):165-74. doi: 10.1001/jama.2018.18743.

Disease-modifying therapies give patients with relapsing-remitting multiple sclerosis a lower risk of developing secondary progressive disease that may only be topped in specific patients with highly active disease by the use of nonmyeloablative hematopoietic stem cell transplantation, according to findings from two studies published online Jan. 15 in JAMA.

copyright Zerbor/Thinkstock

The first study found that interferon-beta, glatiramer acetate (Copaxone), fingolimod (Gilenya), natalizumab (Tysabri), and alemtuzumab (Lemtrada) are associated with a lower risk of conversion to secondary progressive MS, compared with no treatment. Initial treatment with the newer therapies provided a greater risk reduction, compared with initial treatment with interferon-beta or glatiramer acetate.

The second study, described as “the first randomized trial of HSCT [nonmyeloablative hematopoietic stem cell transplantation] in patients with relapsing-remitting MS,” suggests that HSCT prolongs the time to disease progression, compared with disease-modifying therapies (DMTs). It also suggests that HSCT can lead to clinical improvement.
 

DMTs reduced risk of conversion to secondary progressive MS

Few previous studies have examined the association between DMTs and the risk of conversion from relapsing-remitting MS to secondary progressive MS. Those that have analyzed this association have not used a validated definition of secondary progressive MS. J. William L. Brown, MD, of the University of Cambridge, England, and his colleagues used a validated definition of secondary progressive MS that was published in 2016 to investigate how DMTs affect the rate of conversion, compared with no treatment. The researchers also compared the risk reduction provided by fingolimod, alemtuzumab, or natalizumab with that provided by interferon-beta or glatiramer acetate.

Dr. Brown and his colleagues analyzed prospectively collected clinical data from an international observational cohort study called MSBase. Eligible participants had relapsing-remitting MS, the complete MSBase minimum data set, at least one Expanded Disability Status Scale (EDSS) score recorded within 6 months before baseline, and at least two EDSS scores recorded after baseline. Participants initiated a DMT or began clinical monitoring during 1988-2012. The population had a minimum follow-up duration of 4 years. Patients who stopped their initial therapy within 6 months and those participating in clinical trials were excluded.

The primary outcome was conversion to secondary progressive MS. Dr. Brown and his colleagues defined this outcome as an EDSS increase of 1 point for participants with a baseline EDSS score of 5.5 or less and as an increase of 0.5 points for participants with a baseline EDSS score higher than 5.5. This increase had to occur in the absence of relapses and be confirmed at a subsequent visit 3 or fewer months later. In addition, the increased EDSS score had to be 4 or more.

After excluding ineligible participants, the investigators matched 1,555 patients from 68 centers in 21 countries. Each therapy analyzed was associated with reduced risk of converting to secondary progressive MS, compared with no treatment. The hazard ratios for conversion were 0.71 for interferon-beta or glatiramer acetate, 0.37 for fingolimod, 0.61 for natalizumab, and 0.52 for alemtuzumab, compared with no treatment.

Treatment with interferon-beta or glatiramer acetate within 5 years of disease onset was associated with a reduced risk of conversion (HR, 0.77), compared with treatment later than 5 years after disease onset. Similarly, patients who escalated treatment from interferon-beta or glatiramer acetate to any of the other three DMTs within 5 years of disease onset had a significantly lower risk of conversion (HR, 0.76) than did those who escalated later. Furthermore, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly reduced risk of conversion (HR, 0.66), compared with initial treatment with interferon-beta or glatiramer acetate.

One of the study’s limitations is its observational design, which precludes the determination of causality, Dr. Brown and his colleagues said. In addition, functional score subcomponents of the EDSS were unavailable, which prevented the researchers from using the definition of secondary progressive MS with the best combination of sensitivity, specificity, and accuracy. Some analyses were limited by small numbers of patients, and the study did not evaluate the risks associated with DMTs. Nevertheless, “these findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

Financial support for this study was provided by the National Health and Medical Research Council of Australia and the University of Melbourne. Dr. Brown received a Next Generation Fellowship funded by the Grand Charity of the Freemasons and an MSBase 2017 Fellowship. Alemtuzumab studies conducted in Cambridge were supported by the National Institute for Health Research Cambridge Biomedical Research Centre and the MS Society UK.
 

HSCT delayed disease progression

In a previous case series, Richard K. Burt, MD, of Northwestern University in Chicago, and his colleagues found that patients with relapsing-remitting MS who underwent nonmyeloablative HSCT had neurologic improvement and a 70% likelihood of having a 4-year period of disease remission. Dr. Burt and his colleagues undertook the MS international stem cell transplant trial to compare the effects of nonmyeloablative HSCT with those of continued DMT treatment on disease progression in participants with highly active relapsing-remitting MS.

The researchers enrolled 110 participants at four international centers into their open-label trial. Eligible participants had two or more clinical relapses or one relapse and at least one gadolinium-enhancing lesion at a separate time within the previous 12 months, despite DMT treatment. The investigators also required participants to have an EDSS score between 2.0 and 6.0. Patients with primary or secondary progressive MS were excluded.

Dr. Burt and his colleagues randomized participants to receive HSCT or an approved DMT that was more effective or in a different class than the one they were receiving at baseline. Ocrelizumab (Ocrevus) was not administered during the study because it had not yet been approved. The investigators excluded alemtuzumab because of its association with persistent lymphopenia and autoimmune disorders. After 1 year of treatment, patients receiving a DMT who had disability progression could cross over to the HSCT arm. Patients randomized to HSCT stopped taking their usual DMT.

Time to disease progression was the study’s primary endpoint. The investigators defined disease progression as an increase in EDSS score of at least 1 point on two evaluations 6 months apart after at least 1 year of treatment. The increase was required to result from MS. The neurologist who recorded participants’ EDSS evaluations was blinded to treatment group assignment.

The researchers randomized 55 patients to each study arm. Approximately 66% of participants were women, and the sample’s mean age was 36 years. There were no significant baseline differences between groups on demographic, clinical, or imaging characteristics. Three patients in the HSCT group were withdrawn from the study, and four in the DMT group were lost to follow-up after seeking HSCT at outside facilities.

Three patients in the HSCT group and 34 patients in the DMT group had disease progression. Mean follow-up duration was 2.8 years. The investigators could not calculate the median time to progression in the HSCT group because too few events occurred. Median time to progression was 24 months in the DMT group (HR, 0.07). During the first year, mean EDSS scores decreased (indicating improvement) from 3.38 to 2.36 in the HSCT group. Mean EDSS scores increased from 3.31 to 3.98 in the DMT group. No participants died, and no patients who received HSCT-developed nonhematopoietic grade 4 toxicities.

“To our knowledge, this is the first randomized trial of HSCT in patients with relapsing-remitting MS,” Dr. Burt and his colleagues said. Although observational studies have found similar EDSS improvements following HSCT, “this degree of improvement has not been demonstrated in pharmaceutical trials even with more intensive DMT such as alemtuzumab,” they concluded.

The Danhakl Family Foundation, the Cumming Foundation, the McNamara Purcell Foundation, Morgan Stanley, and the National Institute for Health Research Sheffield Clinical Research Facility provided financial support for this study. No pharmaceutical companies supported the study.

egreb@mdedge.com

SOURCEs: Brown JWL et al. JAMA. 2019;321(2):175-87. doi: 10.1001/jama.2018.20588.; and Burt RK et al. JAMA. 2019;321(2):165-74. doi: 10.1001/jama.2018.18743.

BERLIN—Autologous hematopoietic stem cell transplantation (HSCT) could prevent disease activity and promote functional recovery in patients with aggressive multiple sclerosis (MS), according to a retrospective case series presented at ECTRIMS 2018.

A review article suggested that the likelihood of achieving no evidence of disease activity (NEDA) after two years of treatment ranges between 10% and 60% for traditional disease-modifying therapies. In comparison, between 70% and 90% of patients who receive HSCT achieve this outcome.

Like other highly effective therapies, HSCT has been considered to entail significant safety risks. When the European Society for Blood and Marrow Transplantation (EBMT) reviewed their data, however, they identified one death related to HSCT between 2012 and 2016. The estimated risk of death from HSCT is thus approximately 0.2%. “Mortality associated with transplantation has decreased so much that it is almost into the range of other standard disease-modifying therapies,” said Joyutpal Das, MBBS, a neuroscientist at Royal Hallamshire Hospital in Sheffield, United Kingdom.

EBMT recommended that neurologists consider HSCT for patients with highly active radiologic and clinical disease who have failed to respond to standard disease-modifying therapy. The treatment can be considered as first-line therapy for patients with exceptionally active disease who have become disabled, they added.

A Retrospective Case Series

To examine the efficacy of HSCT in this patient population, Dr. Das and colleagues conducted a retrospective case series of 20 patients with MS from five centers in various countries. The patients’ treating physicians decided that HSCT should be their first-line therapy. Dr. Das and colleagues used NEDA-3 (which includes relapses, disability progression, and MRI activity) as their primary outcome. Each patient underwent brain MRI during the first six months of treatment and at six- to 12-month intervals thereafter.

The case series included equal numbers of men and women. All patients had frequent relapses, incomplete recovery, and multiple gadolinium enhancing lesions on serial MRI scans. The lesions often affected the brainstem, cerebellum, and spine. Patients’ median age of diagnosis and median age of treatment were 28. The time between the first onset of symptoms and treatment was nine months, and that between diagnosis and treatment was five months. Patients’ median pretreatment Expanded Disability Status Scale (EDSS) score was 6.5. Median follow-up duration was 2.5 years.

EDSS Score Improved

Three patients had new lesions during the first six months of treatment, but no patients had new lesions on subsequent MRI scans. “It has been suggested … that if you want to use NEDA to measure efficacy, the patient should have rebaseline imaging after the initiation of treatment,” said Dr. Das. “If we use our six-month scan as rebaseline imaging, then we have no further disease activity on MRI scan.”

After treatment initiation, the median EDSS score decreased from 6.5 to 2. Patients’ median improvement on EDSS score was 2.5 points, which was statistically significant. Seven patients had an EDSS score improvement of 3 points or greater. EDSS score improved for all but one patient. The results suggest that HSCT induced rapid and sustained remission, said Dr. Das.

The investigators observed typical transplant-related toxicity in the population, and no patient died. One woman conceived and gave birth to a healthy baby, and one man fathered a healthy baby.

—Erik Greb

Suggested Reading

Sormani MP, Muraro PA, Saccardi R, Mancardi G. NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs. Mult Scler. 2017;23(2):201-204.

BERLIN—Autologous hematopoietic stem cell transplantation (HSCT) could prevent disease activity and promote functional recovery in patients with aggressive multiple sclerosis (MS), according to a retrospective case series presented at ECTRIMS 2018.

A review article suggested that the likelihood of achieving no evidence of disease activity (NEDA) after two years of treatment ranges between 10% and 60% for traditional disease-modifying therapies. In comparison, between 70% and 90% of patients who receive HSCT achieve this outcome.

Like other highly effective therapies, HSCT has been considered to entail significant safety risks. When the European Society for Blood and Marrow Transplantation (EBMT) reviewed their data, however, they identified one death related to HSCT between 2012 and 2016. The estimated risk of death from HSCT is thus approximately 0.2%. “Mortality associated with transplantation has decreased so much that it is almost into the range of other standard disease-modifying therapies,” said Joyutpal Das, MBBS, a neuroscientist at Royal Hallamshire Hospital in Sheffield, United Kingdom.

EBMT recommended that neurologists consider HSCT for patients with highly active radiologic and clinical disease who have failed to respond to standard disease-modifying therapy. The treatment can be considered as first-line therapy for patients with exceptionally active disease who have become disabled, they added.

A Retrospective Case Series

To examine the efficacy of HSCT in this patient population, Dr. Das and colleagues conducted a retrospective case series of 20 patients with MS from five centers in various countries. The patients’ treating physicians decided that HSCT should be their first-line therapy. Dr. Das and colleagues used NEDA-3 (which includes relapses, disability progression, and MRI activity) as their primary outcome. Each patient underwent brain MRI during the first six months of treatment and at six- to 12-month intervals thereafter.

The case series included equal numbers of men and women. All patients had frequent relapses, incomplete recovery, and multiple gadolinium enhancing lesions on serial MRI scans. The lesions often affected the brainstem, cerebellum, and spine. Patients’ median age of diagnosis and median age of treatment were 28. The time between the first onset of symptoms and treatment was nine months, and that between diagnosis and treatment was five months. Patients’ median pretreatment Expanded Disability Status Scale (EDSS) score was 6.5. Median follow-up duration was 2.5 years.

EDSS Score Improved

Three patients had new lesions during the first six months of treatment, but no patients had new lesions on subsequent MRI scans. “It has been suggested … that if you want to use NEDA to measure efficacy, the patient should have rebaseline imaging after the initiation of treatment,” said Dr. Das. “If we use our six-month scan as rebaseline imaging, then we have no further disease activity on MRI scan.”

After treatment initiation, the median EDSS score decreased from 6.5 to 2. Patients’ median improvement on EDSS score was 2.5 points, which was statistically significant. Seven patients had an EDSS score improvement of 3 points or greater. EDSS score improved for all but one patient. The results suggest that HSCT induced rapid and sustained remission, said Dr. Das.

The investigators observed typical transplant-related toxicity in the population, and no patient died. One woman conceived and gave birth to a healthy baby, and one man fathered a healthy baby.

—Erik Greb

Suggested Reading

Sormani MP, Muraro PA, Saccardi R, Mancardi G. NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs. Mult Scler. 2017;23(2):201-204.

BERLIN—Autologous hematopoietic stem cell transplantation (HSCT) could prevent disease activity and promote functional recovery in patients with aggressive multiple sclerosis (MS), according to a retrospective case series presented at ECTRIMS 2018.

A review article suggested that the likelihood of achieving no evidence of disease activity (NEDA) after two years of treatment ranges between 10% and 60% for traditional disease-modifying therapies. In comparison, between 70% and 90% of patients who receive HSCT achieve this outcome.

Like other highly effective therapies, HSCT has been considered to entail significant safety risks. When the European Society for Blood and Marrow Transplantation (EBMT) reviewed their data, however, they identified one death related to HSCT between 2012 and 2016. The estimated risk of death from HSCT is thus approximately 0.2%. “Mortality associated with transplantation has decreased so much that it is almost into the range of other standard disease-modifying therapies,” said Joyutpal Das, MBBS, a neuroscientist at Royal Hallamshire Hospital in Sheffield, United Kingdom.

EBMT recommended that neurologists consider HSCT for patients with highly active radiologic and clinical disease who have failed to respond to standard disease-modifying therapy. The treatment can be considered as first-line therapy for patients with exceptionally active disease who have become disabled, they added.

A Retrospective Case Series

To examine the efficacy of HSCT in this patient population, Dr. Das and colleagues conducted a retrospective case series of 20 patients with MS from five centers in various countries. The patients’ treating physicians decided that HSCT should be their first-line therapy. Dr. Das and colleagues used NEDA-3 (which includes relapses, disability progression, and MRI activity) as their primary outcome. Each patient underwent brain MRI during the first six months of treatment and at six- to 12-month intervals thereafter.

The case series included equal numbers of men and women. All patients had frequent relapses, incomplete recovery, and multiple gadolinium enhancing lesions on serial MRI scans. The lesions often affected the brainstem, cerebellum, and spine. Patients’ median age of diagnosis and median age of treatment were 28. The time between the first onset of symptoms and treatment was nine months, and that between diagnosis and treatment was five months. Patients’ median pretreatment Expanded Disability Status Scale (EDSS) score was 6.5. Median follow-up duration was 2.5 years.

EDSS Score Improved

Three patients had new lesions during the first six months of treatment, but no patients had new lesions on subsequent MRI scans. “It has been suggested … that if you want to use NEDA to measure efficacy, the patient should have rebaseline imaging after the initiation of treatment,” said Dr. Das. “If we use our six-month scan as rebaseline imaging, then we have no further disease activity on MRI scan.”

After treatment initiation, the median EDSS score decreased from 6.5 to 2. Patients’ median improvement on EDSS score was 2.5 points, which was statistically significant. Seven patients had an EDSS score improvement of 3 points or greater. EDSS score improved for all but one patient. The results suggest that HSCT induced rapid and sustained remission, said Dr. Das.

The investigators observed typical transplant-related toxicity in the population, and no patient died. One woman conceived and gave birth to a healthy baby, and one man fathered a healthy baby.

—Erik Greb

Suggested Reading

Sormani MP, Muraro PA, Saccardi R, Mancardi G. NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs. Mult Scler. 2017;23(2):201-204.

BERLIN—European registry data do not support the hypothesis that exposure to interferon beta before conception or during pregnancy adversely affects pregnancy outcome or infant outcome, according to an analysis presented at ECTRIMS 2018.

In women, diagnosis of multiple sclerosis (MS) and treatment initiation often occur during childbearing years, but neurologists have not reached consensus about treatment before or during pregnancy. The European Interferon Beta Pregnancy Registry was created to gather evidence about the effect of this treatment on maternal and fetal outcomes. A separate population-based cohort study examined health care registry data from Finland and Sweden (ie, Nordic registries) for the same purpose.

An Analysis of Prospective Data

Kerstin Hellwig, MD, Senior Consultant Neurologist and researcher at St. Joseph and St. Elizabeth Hospital and Ruhr University in Bochum, Germany, and colleagues examined these databases to evaluate the prevalence of pregnancy and infant outcomes in women with MS who had been exposed to interferon beta. The investigators analyzed 948 pregnancy reports with recorded pregnancy outcomes from the European Interferon Beta Pregnancy Registry. They also examined 875 pregnancy events in the Nordic registries among patients exposed to interferon beta and other treatments and 1,831 events among untreated patients.

Treatment Did Not Affect Birth Weight

Approximately 82% of pregnancies in the European registry had an outcome of live birth without congenital anomalies. The prevalence of spontaneous abortions and live births with congenital anomalies were similar to those reported in the general population.

About 98% of pregnancies in the exposed cohort of the Nordic registries had an outcome of live birth without congenital anomalies. This result is similar to the corresponding 97% rate in the nonexposed cohort. The prevalence of spontaneous abortions and congenital anomalies also were similar between the exposed and nonexposed cohorts of the Nordic registries.

Birth weights ranged from 580 g to 5,160 g in the Nordic registries. The proportion of babies with low or very low birth weight was 5.0% in the interferon-exposed cohort, 4.7% among babies exposed to interferon and other treatments, and 5.8% among nonexposed babies. Mean birth weight was 3,421.2 g in the interferon-exposed cohort, 3,434.3 g in the cohort exposed to interferon and other treatments, and 3,389.3 g in the nonexposed cohort. These weights were consistent with results from the prospective German pregnancy registry, according to the authors. Birth weights were not recorded systematically in the European registry.

“The European Inter­feron Beta Pregnancy Registry showed no evidence that interferon beta exposure before conception or during pregnancy adversely affected pregnancy or infant outcomes,” said Dr. Hellwig and colleagues. “This is consistent with data collected from the Nordic registers.”

This study was supported by Merck in Darmstadt, Germany. Additional funding for analysis, project management, and medical writing was provided by Bayer, Biogen, Merck, and Novartis Pharma.

—Erik Greb

Suggested Reading

Alroughani R, Altintas A, Al Jumah M, et al. Pregnancy and the use of disease-modifying therapies in patients with multiple sclerosis: benefits versus risks. Mult Scler Int. 2016;2016:1034912.

Friend S, Richman S, Bloomgren G, et al. Evaluation of pregnancy outcomes from the Tysabri (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016;16(1):150.

BERLIN—European registry data do not support the hypothesis that exposure to interferon beta before conception or during pregnancy adversely affects pregnancy outcome or infant outcome, according to an analysis presented at ECTRIMS 2018.

In women, diagnosis of multiple sclerosis (MS) and treatment initiation often occur during childbearing years, but neurologists have not reached consensus about treatment before or during pregnancy. The European Interferon Beta Pregnancy Registry was created to gather evidence about the effect of this treatment on maternal and fetal outcomes. A separate population-based cohort study examined health care registry data from Finland and Sweden (ie, Nordic registries) for the same purpose.

An Analysis of Prospective Data

Kerstin Hellwig, MD, Senior Consultant Neurologist and researcher at St. Joseph and St. Elizabeth Hospital and Ruhr University in Bochum, Germany, and colleagues examined these databases to evaluate the prevalence of pregnancy and infant outcomes in women with MS who had been exposed to interferon beta. The investigators analyzed 948 pregnancy reports with recorded pregnancy outcomes from the European Interferon Beta Pregnancy Registry. They also examined 875 pregnancy events in the Nordic registries among patients exposed to interferon beta and other treatments and 1,831 events among untreated patients.

Treatment Did Not Affect Birth Weight

Approximately 82% of pregnancies in the European registry had an outcome of live birth without congenital anomalies. The prevalence of spontaneous abortions and live births with congenital anomalies were similar to those reported in the general population.

About 98% of pregnancies in the exposed cohort of the Nordic registries had an outcome of live birth without congenital anomalies. This result is similar to the corresponding 97% rate in the nonexposed cohort. The prevalence of spontaneous abortions and congenital anomalies also were similar between the exposed and nonexposed cohorts of the Nordic registries.

Birth weights ranged from 580 g to 5,160 g in the Nordic registries. The proportion of babies with low or very low birth weight was 5.0% in the interferon-exposed cohort, 4.7% among babies exposed to interferon and other treatments, and 5.8% among nonexposed babies. Mean birth weight was 3,421.2 g in the interferon-exposed cohort, 3,434.3 g in the cohort exposed to interferon and other treatments, and 3,389.3 g in the nonexposed cohort. These weights were consistent with results from the prospective German pregnancy registry, according to the authors. Birth weights were not recorded systematically in the European registry.

“The European Inter­feron Beta Pregnancy Registry showed no evidence that interferon beta exposure before conception or during pregnancy adversely affected pregnancy or infant outcomes,” said Dr. Hellwig and colleagues. “This is consistent with data collected from the Nordic registers.”

This study was supported by Merck in Darmstadt, Germany. Additional funding for analysis, project management, and medical writing was provided by Bayer, Biogen, Merck, and Novartis Pharma.

—Erik Greb

Suggested Reading

Alroughani R, Altintas A, Al Jumah M, et al. Pregnancy and the use of disease-modifying therapies in patients with multiple sclerosis: benefits versus risks. Mult Scler Int. 2016;2016:1034912.

Friend S, Richman S, Bloomgren G, et al. Evaluation of pregnancy outcomes from the Tysabri (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016;16(1):150.

BERLIN—European registry data do not support the hypothesis that exposure to interferon beta before conception or during pregnancy adversely affects pregnancy outcome or infant outcome, according to an analysis presented at ECTRIMS 2018.

In women, diagnosis of multiple sclerosis (MS) and treatment initiation often occur during childbearing years, but neurologists have not reached consensus about treatment before or during pregnancy. The European Interferon Beta Pregnancy Registry was created to gather evidence about the effect of this treatment on maternal and fetal outcomes. A separate population-based cohort study examined health care registry data from Finland and Sweden (ie, Nordic registries) for the same purpose.

An Analysis of Prospective Data

Kerstin Hellwig, MD, Senior Consultant Neurologist and researcher at St. Joseph and St. Elizabeth Hospital and Ruhr University in Bochum, Germany, and colleagues examined these databases to evaluate the prevalence of pregnancy and infant outcomes in women with MS who had been exposed to interferon beta. The investigators analyzed 948 pregnancy reports with recorded pregnancy outcomes from the European Interferon Beta Pregnancy Registry. They also examined 875 pregnancy events in the Nordic registries among patients exposed to interferon beta and other treatments and 1,831 events among untreated patients.

Treatment Did Not Affect Birth Weight

Approximately 82% of pregnancies in the European registry had an outcome of live birth without congenital anomalies. The prevalence of spontaneous abortions and live births with congenital anomalies were similar to those reported in the general population.

About 98% of pregnancies in the exposed cohort of the Nordic registries had an outcome of live birth without congenital anomalies. This result is similar to the corresponding 97% rate in the nonexposed cohort. The prevalence of spontaneous abortions and congenital anomalies also were similar between the exposed and nonexposed cohorts of the Nordic registries.

Birth weights ranged from 580 g to 5,160 g in the Nordic registries. The proportion of babies with low or very low birth weight was 5.0% in the interferon-exposed cohort, 4.7% among babies exposed to interferon and other treatments, and 5.8% among nonexposed babies. Mean birth weight was 3,421.2 g in the interferon-exposed cohort, 3,434.3 g in the cohort exposed to interferon and other treatments, and 3,389.3 g in the nonexposed cohort. These weights were consistent with results from the prospective German pregnancy registry, according to the authors. Birth weights were not recorded systematically in the European registry.

“The European Inter­feron Beta Pregnancy Registry showed no evidence that interferon beta exposure before conception or during pregnancy adversely affected pregnancy or infant outcomes,” said Dr. Hellwig and colleagues. “This is consistent with data collected from the Nordic registers.”

This study was supported by Merck in Darmstadt, Germany. Additional funding for analysis, project management, and medical writing was provided by Bayer, Biogen, Merck, and Novartis Pharma.

—Erik Greb

Suggested Reading

Alroughani R, Altintas A, Al Jumah M, et al. Pregnancy and the use of disease-modifying therapies in patients with multiple sclerosis: benefits versus risks. Mult Scler Int. 2016;2016:1034912.

Friend S, Richman S, Bloomgren G, et al. Evaluation of pregnancy outcomes from the Tysabri (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016;16(1):150.