Multiple Sclerosis

Most disability accumulation in relapsing multiple sclerosis (MS) is not associated with overt relapses, challenging the current clinical distinction of relapsing and progressive forms of the disease, a new analysis shows. “We have to abandon the distinction between relapsing and progressive MS being different populations,” said lead author Ludwig Kappos, MD, University of Basel (Switzerland). “The disease appears to be more of a continuum of disability progression, which is sometimes also accompanied by relapses.”

The analysis was published online June 8 in JAMA Neurology.
 

Assessing disability progression

Noting that there are mounting data to suggest patients with relapsing MS frequently experience worsening disability over time – even when relapse activity appears well controlled – the researchers aimed to investigate the relative contributions of progression independent of relapse activity and relapse-associated worsening to overall accumulating disability in patients with relapsing multiple sclerosis. To do this, they analyzed data from two identical randomized clinical trials (OPERA I and OPERA II) conducted between 2011 and 2015, which compared treatment with the new B-cell–depleting therapy ocrelizumab with interferon beta-1a in 1,656 patients with relapsing MS.

Confirmed disability accumulation was defined by an increase in 1 or more of 3 measures (Expanded Disability Status Scale, timed 25-ft walk, or 9-hole peg test), confirmed after 3 or 6 months, and was classified as being related to a clinical relapse or occurring in the absence of a relapse.

Results showed that after 96 weeks (1.8 years) of treatment, 12-week composite confirmed disability accumulation had occurred in 29.6% of patients receiving interferon beta-1a and 21.1% of those given ocrelizumab; 24-week composite confirmed disability accumulation occurred in 22.7% of interferon beta-1a patients and 16.2% of the ocrelizumab group.

In both treatment groups, the vast majority of events contributing to disability accumulation occurred independently of relapse activity. In the interferon group, 78% of events contributing to 12-week confirmed disability accumulation and 80.6% of events contributing to 24-week confirmed disability accumulation occurred in the absence of clinical relapses, with the corresponding figures in the ocrelizumab group being 88.0% (12 weeks) and 89.1% (24 weeks).

Only a minority of patients (about 17% in both groups) had confirmed disability accumulation accompanied by clinical relapses. Very few patients with confirmed disability accumulation (4% to 5%) experienced disability worsening both associated and independent of relapses. Ocrelizumab was associated with a reduced risk of both relapse-associated and relapse-independent confirmed disability accumulation, compared with interferon beta-1a.

“We found that there was progression of disability in both groups, and the really astonishing finding was that although all patients were classified as having relapsing remitting MS, actually most of the disability progression occurred without preceding relapses,” Dr. Kappos commented. He noted that there have been two previous observational studies that have shown a high rate of disability progressions without temporal association to relapses in relapsing remitting patients, but this is the first time that this progression of disability independent of relapses has been shown in the controlled setting of two prospective, randomized clinical trials over a 2-year period.

“While we expected to see some disability progression independent of relapses, we were surprised to see that the disability progression occurring in both studies was almost exclusively happening without temporal relation to relapses. That was certainly an unexpected finding,” Dr. Kappos said. “These observations make it difficult to keep the current definitions of ‘relapsing remitting’ and ‘secondary progressive’ MS, [ones] that suggest a clear-cut distinction marked by the presence or absence of relapses. This can no longer be justified,” he stressed.

“We are not saying that relapses do not contribute to disability progression. There are a lot of data to support the fact that they do. But I think what we might be seeing is that the drug therapy is quite effective in reducing disability due to relapses but only partially effective in reducing progression independent of relapses,” Dr. Kappos explained.

Although there have been many advances in reducing relapses with drug therapy, focus now needs to shift to the other more continuous process of disability progression independent of relapses, Dr. Kappos said. “There is still a lot of room for improvement here.”

“If continuous progression independent of relapses is already present in the early phases of MS, it is reasonable to study the effects of intervention on steady progression already in this early phase,” he noted. “This might help to capture patients at earlier stages who better respond to treatment aimed at halting progression.”

Dr. Kappos also called for more subtle measurements of disability than the EDSS alone, including measures such as the 9-hole peg test and the 25-ft walk as they did in this analysis. But other measures could also be added that would characterize continuous disease activity and progression, such as laboratory values (e.g., neurofilament light chain) and advanced, more tissue-specific quantitative MRI techniques and digital biomarkers to detect subtle changes in neurologic function.
 

An artificial distinction?

Commenting on the study, Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, said he too sees very little distinction between relapsing remitting and progressive forms of the disease.

“This study confirms what has been suspected for quite a few years –that if one looks sufficiently and carefully, there is gradual worsening of some aspects of the disease in many patients from the earliest stages,” Dr. Cohen said. “Conversely, some patients with progressive MS have superimposed relapses or MRI lesion activity.

“Thus, the distinction between relapsing-remitting and progressive MS subtypes appears artificial,” he concluded.

This study was sponsored by F. Hoffmann–La Roche. Dr. Kappos has received research support from the company.

This article first appeared on Medscape.com.

Most disability accumulation in relapsing multiple sclerosis (MS) is not associated with overt relapses, challenging the current clinical distinction of relapsing and progressive forms of the disease, a new analysis shows. “We have to abandon the distinction between relapsing and progressive MS being different populations,” said lead author Ludwig Kappos, MD, University of Basel (Switzerland). “The disease appears to be more of a continuum of disability progression, which is sometimes also accompanied by relapses.”

The analysis was published online June 8 in JAMA Neurology.
 

Assessing disability progression

Noting that there are mounting data to suggest patients with relapsing MS frequently experience worsening disability over time – even when relapse activity appears well controlled – the researchers aimed to investigate the relative contributions of progression independent of relapse activity and relapse-associated worsening to overall accumulating disability in patients with relapsing multiple sclerosis. To do this, they analyzed data from two identical randomized clinical trials (OPERA I and OPERA II) conducted between 2011 and 2015, which compared treatment with the new B-cell–depleting therapy ocrelizumab with interferon beta-1a in 1,656 patients with relapsing MS.

Confirmed disability accumulation was defined by an increase in 1 or more of 3 measures (Expanded Disability Status Scale, timed 25-ft walk, or 9-hole peg test), confirmed after 3 or 6 months, and was classified as being related to a clinical relapse or occurring in the absence of a relapse.

Results showed that after 96 weeks (1.8 years) of treatment, 12-week composite confirmed disability accumulation had occurred in 29.6% of patients receiving interferon beta-1a and 21.1% of those given ocrelizumab; 24-week composite confirmed disability accumulation occurred in 22.7% of interferon beta-1a patients and 16.2% of the ocrelizumab group.

In both treatment groups, the vast majority of events contributing to disability accumulation occurred independently of relapse activity. In the interferon group, 78% of events contributing to 12-week confirmed disability accumulation and 80.6% of events contributing to 24-week confirmed disability accumulation occurred in the absence of clinical relapses, with the corresponding figures in the ocrelizumab group being 88.0% (12 weeks) and 89.1% (24 weeks).

Only a minority of patients (about 17% in both groups) had confirmed disability accumulation accompanied by clinical relapses. Very few patients with confirmed disability accumulation (4% to 5%) experienced disability worsening both associated and independent of relapses. Ocrelizumab was associated with a reduced risk of both relapse-associated and relapse-independent confirmed disability accumulation, compared with interferon beta-1a.

“We found that there was progression of disability in both groups, and the really astonishing finding was that although all patients were classified as having relapsing remitting MS, actually most of the disability progression occurred without preceding relapses,” Dr. Kappos commented. He noted that there have been two previous observational studies that have shown a high rate of disability progressions without temporal association to relapses in relapsing remitting patients, but this is the first time that this progression of disability independent of relapses has been shown in the controlled setting of two prospective, randomized clinical trials over a 2-year period.

“While we expected to see some disability progression independent of relapses, we were surprised to see that the disability progression occurring in both studies was almost exclusively happening without temporal relation to relapses. That was certainly an unexpected finding,” Dr. Kappos said. “These observations make it difficult to keep the current definitions of ‘relapsing remitting’ and ‘secondary progressive’ MS, [ones] that suggest a clear-cut distinction marked by the presence or absence of relapses. This can no longer be justified,” he stressed.

“We are not saying that relapses do not contribute to disability progression. There are a lot of data to support the fact that they do. But I think what we might be seeing is that the drug therapy is quite effective in reducing disability due to relapses but only partially effective in reducing progression independent of relapses,” Dr. Kappos explained.

Although there have been many advances in reducing relapses with drug therapy, focus now needs to shift to the other more continuous process of disability progression independent of relapses, Dr. Kappos said. “There is still a lot of room for improvement here.”

“If continuous progression independent of relapses is already present in the early phases of MS, it is reasonable to study the effects of intervention on steady progression already in this early phase,” he noted. “This might help to capture patients at earlier stages who better respond to treatment aimed at halting progression.”

Dr. Kappos also called for more subtle measurements of disability than the EDSS alone, including measures such as the 9-hole peg test and the 25-ft walk as they did in this analysis. But other measures could also be added that would characterize continuous disease activity and progression, such as laboratory values (e.g., neurofilament light chain) and advanced, more tissue-specific quantitative MRI techniques and digital biomarkers to detect subtle changes in neurologic function.
 

An artificial distinction?

Commenting on the study, Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, said he too sees very little distinction between relapsing remitting and progressive forms of the disease.

“This study confirms what has been suspected for quite a few years –that if one looks sufficiently and carefully, there is gradual worsening of some aspects of the disease in many patients from the earliest stages,” Dr. Cohen said. “Conversely, some patients with progressive MS have superimposed relapses or MRI lesion activity.

“Thus, the distinction between relapsing-remitting and progressive MS subtypes appears artificial,” he concluded.

This study was sponsored by F. Hoffmann–La Roche. Dr. Kappos has received research support from the company.

This article first appeared on Medscape.com.

Most disability accumulation in relapsing multiple sclerosis (MS) is not associated with overt relapses, challenging the current clinical distinction of relapsing and progressive forms of the disease, a new analysis shows. “We have to abandon the distinction between relapsing and progressive MS being different populations,” said lead author Ludwig Kappos, MD, University of Basel (Switzerland). “The disease appears to be more of a continuum of disability progression, which is sometimes also accompanied by relapses.”

The analysis was published online June 8 in JAMA Neurology.
 

Assessing disability progression

Noting that there are mounting data to suggest patients with relapsing MS frequently experience worsening disability over time – even when relapse activity appears well controlled – the researchers aimed to investigate the relative contributions of progression independent of relapse activity and relapse-associated worsening to overall accumulating disability in patients with relapsing multiple sclerosis. To do this, they analyzed data from two identical randomized clinical trials (OPERA I and OPERA II) conducted between 2011 and 2015, which compared treatment with the new B-cell–depleting therapy ocrelizumab with interferon beta-1a in 1,656 patients with relapsing MS.

Confirmed disability accumulation was defined by an increase in 1 or more of 3 measures (Expanded Disability Status Scale, timed 25-ft walk, or 9-hole peg test), confirmed after 3 or 6 months, and was classified as being related to a clinical relapse or occurring in the absence of a relapse.

Results showed that after 96 weeks (1.8 years) of treatment, 12-week composite confirmed disability accumulation had occurred in 29.6% of patients receiving interferon beta-1a and 21.1% of those given ocrelizumab; 24-week composite confirmed disability accumulation occurred in 22.7% of interferon beta-1a patients and 16.2% of the ocrelizumab group.

In both treatment groups, the vast majority of events contributing to disability accumulation occurred independently of relapse activity. In the interferon group, 78% of events contributing to 12-week confirmed disability accumulation and 80.6% of events contributing to 24-week confirmed disability accumulation occurred in the absence of clinical relapses, with the corresponding figures in the ocrelizumab group being 88.0% (12 weeks) and 89.1% (24 weeks).

Only a minority of patients (about 17% in both groups) had confirmed disability accumulation accompanied by clinical relapses. Very few patients with confirmed disability accumulation (4% to 5%) experienced disability worsening both associated and independent of relapses. Ocrelizumab was associated with a reduced risk of both relapse-associated and relapse-independent confirmed disability accumulation, compared with interferon beta-1a.

“We found that there was progression of disability in both groups, and the really astonishing finding was that although all patients were classified as having relapsing remitting MS, actually most of the disability progression occurred without preceding relapses,” Dr. Kappos commented. He noted that there have been two previous observational studies that have shown a high rate of disability progressions without temporal association to relapses in relapsing remitting patients, but this is the first time that this progression of disability independent of relapses has been shown in the controlled setting of two prospective, randomized clinical trials over a 2-year period.

“While we expected to see some disability progression independent of relapses, we were surprised to see that the disability progression occurring in both studies was almost exclusively happening without temporal relation to relapses. That was certainly an unexpected finding,” Dr. Kappos said. “These observations make it difficult to keep the current definitions of ‘relapsing remitting’ and ‘secondary progressive’ MS, [ones] that suggest a clear-cut distinction marked by the presence or absence of relapses. This can no longer be justified,” he stressed.

“We are not saying that relapses do not contribute to disability progression. There are a lot of data to support the fact that they do. But I think what we might be seeing is that the drug therapy is quite effective in reducing disability due to relapses but only partially effective in reducing progression independent of relapses,” Dr. Kappos explained.

Although there have been many advances in reducing relapses with drug therapy, focus now needs to shift to the other more continuous process of disability progression independent of relapses, Dr. Kappos said. “There is still a lot of room for improvement here.”

“If continuous progression independent of relapses is already present in the early phases of MS, it is reasonable to study the effects of intervention on steady progression already in this early phase,” he noted. “This might help to capture patients at earlier stages who better respond to treatment aimed at halting progression.”

Dr. Kappos also called for more subtle measurements of disability than the EDSS alone, including measures such as the 9-hole peg test and the 25-ft walk as they did in this analysis. But other measures could also be added that would characterize continuous disease activity and progression, such as laboratory values (e.g., neurofilament light chain) and advanced, more tissue-specific quantitative MRI techniques and digital biomarkers to detect subtle changes in neurologic function.
 

An artificial distinction?

Commenting on the study, Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, said he too sees very little distinction between relapsing remitting and progressive forms of the disease.

“This study confirms what has been suspected for quite a few years –that if one looks sufficiently and carefully, there is gradual worsening of some aspects of the disease in many patients from the earliest stages,” Dr. Cohen said. “Conversely, some patients with progressive MS have superimposed relapses or MRI lesion activity.

“Thus, the distinction between relapsing-remitting and progressive MS subtypes appears artificial,” he concluded.

This study was sponsored by F. Hoffmann–La Roche. Dr. Kappos has received research support from the company.

This article first appeared on Medscape.com.

The Food and Drug Administration has approved Uplizna (inebilizumab-cdon) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-AQP4 antibody positive. Uplizna is the second approved treatment for the disorder.

Approval was based on results from the global, placebo-controlled N-MOmentum trial, which included 213 anti-AQP4 antibody–positive patients and 17 anti-AQP4 antibody–negative patients who received inebilizumab-cdon or placebo. Just under 90% of patients in the positive group remained relapse free 6 months after the initial dosing, compared with 58% of patients taking placebo. People who took inebilizumab also saw a reduction in NMOSD-related hospitalizations. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative.

Inebilizumab-cdon was safe and well tolerated during the trial, with the most common adverse events being urinary tract infection (20%), nasopharyngitis (13%), infusion reaction (12%), arthralgia (11%), and headache (10%). The drug is approved as twice-yearly maintenance after initial dosing. The prescribing information for Uplizna includes a warning for infusion reactions, potential depletion of certain proteins (hypogammaglobulinemia), and potential increased risk of infection—including progressive multifocal leukoencephalopathy—and potential reactivation of hepatitis B and tuberculosis.

“NMOSD is an extremely challenging disease to treat. Patients experience unpredictable attacks that can lead to permanent disability from blindness and paralysis. In addition, each subsequent attack may result in a cumulative worsening of disability,” Bruce Cree, MD, PhD, lead investigator for the N-MOmentum trial and professor of clinical neurology at the University of California, San Francisco, said in a press release. “Uplizna is an important new treatment option that provides prescribing physicians and patients living with NMOSD a therapy with proven efficacy, a favorable safety profile and a twice-a-year maintenance dosing schedule.”

[email protected]

The Food and Drug Administration has approved Uplizna (inebilizumab-cdon) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-AQP4 antibody positive. Uplizna is the second approved treatment for the disorder.

Approval was based on results from the global, placebo-controlled N-MOmentum trial, which included 213 anti-AQP4 antibody–positive patients and 17 anti-AQP4 antibody–negative patients who received inebilizumab-cdon or placebo. Just under 90% of patients in the positive group remained relapse free 6 months after the initial dosing, compared with 58% of patients taking placebo. People who took inebilizumab also saw a reduction in NMOSD-related hospitalizations. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative.

Inebilizumab-cdon was safe and well tolerated during the trial, with the most common adverse events being urinary tract infection (20%), nasopharyngitis (13%), infusion reaction (12%), arthralgia (11%), and headache (10%). The drug is approved as twice-yearly maintenance after initial dosing. The prescribing information for Uplizna includes a warning for infusion reactions, potential depletion of certain proteins (hypogammaglobulinemia), and potential increased risk of infection—including progressive multifocal leukoencephalopathy—and potential reactivation of hepatitis B and tuberculosis.

“NMOSD is an extremely challenging disease to treat. Patients experience unpredictable attacks that can lead to permanent disability from blindness and paralysis. In addition, each subsequent attack may result in a cumulative worsening of disability,” Bruce Cree, MD, PhD, lead investigator for the N-MOmentum trial and professor of clinical neurology at the University of California, San Francisco, said in a press release. “Uplizna is an important new treatment option that provides prescribing physicians and patients living with NMOSD a therapy with proven efficacy, a favorable safety profile and a twice-a-year maintenance dosing schedule.”

[email protected]

The Food and Drug Administration has approved Uplizna (inebilizumab-cdon) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-AQP4 antibody positive. Uplizna is the second approved treatment for the disorder.

Approval was based on results from the global, placebo-controlled N-MOmentum trial, which included 213 anti-AQP4 antibody–positive patients and 17 anti-AQP4 antibody–negative patients who received inebilizumab-cdon or placebo. Just under 90% of patients in the positive group remained relapse free 6 months after the initial dosing, compared with 58% of patients taking placebo. People who took inebilizumab also saw a reduction in NMOSD-related hospitalizations. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative.

Inebilizumab-cdon was safe and well tolerated during the trial, with the most common adverse events being urinary tract infection (20%), nasopharyngitis (13%), infusion reaction (12%), arthralgia (11%), and headache (10%). The drug is approved as twice-yearly maintenance after initial dosing. The prescribing information for Uplizna includes a warning for infusion reactions, potential depletion of certain proteins (hypogammaglobulinemia), and potential increased risk of infection—including progressive multifocal leukoencephalopathy—and potential reactivation of hepatitis B and tuberculosis.

“NMOSD is an extremely challenging disease to treat. Patients experience unpredictable attacks that can lead to permanent disability from blindness and paralysis. In addition, each subsequent attack may result in a cumulative worsening of disability,” Bruce Cree, MD, PhD, lead investigator for the N-MOmentum trial and professor of clinical neurology at the University of California, San Francisco, said in a press release. “Uplizna is an important new treatment option that provides prescribing physicians and patients living with NMOSD a therapy with proven efficacy, a favorable safety profile and a twice-a-year maintenance dosing schedule.”

[email protected]

Despite the ever-increasing acceptance of medical cannabis and its notably common use in patients with multiple sclerosis (MS), clinicians treating those patients still may be poorly informed about risks, benefits, regulations, and proper uses, experts say.

“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.

As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
 

Misconceptions common among clinicians

Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.

Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.

In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.

Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.

There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.

Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.

Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.

And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.

Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.

However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.

Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.

However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.

He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.

While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.

“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
 

Addiction, distinguishing cannabis from MS symptoms

Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”

Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”

The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.

“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”

“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”

Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.

Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.

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

Despite the ever-increasing acceptance of medical cannabis and its notably common use in patients with multiple sclerosis (MS), clinicians treating those patients still may be poorly informed about risks, benefits, regulations, and proper uses, experts say.

“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.

As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
 

Misconceptions common among clinicians

Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.

Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.

In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.

Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.

There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.

Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.

Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.

And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.

Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.

However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.

Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.

However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.

He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.

While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.

“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
 

Addiction, distinguishing cannabis from MS symptoms

Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”

Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”

The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.

“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”

“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”

Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.

Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.

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

Despite the ever-increasing acceptance of medical cannabis and its notably common use in patients with multiple sclerosis (MS), clinicians treating those patients still may be poorly informed about risks, benefits, regulations, and proper uses, experts say.

“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.

As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
 

Misconceptions common among clinicians

Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.

Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.

In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.

Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.

There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.

Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.

Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.

And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.

Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.

However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.

Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.

However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.

He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.

While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.

“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
 

Addiction, distinguishing cannabis from MS symptoms

Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”

Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”

The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.

“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”

“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”

Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.

Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.

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

The variability in functional performance within and between levels of disability measured by the Expanded Disability Status Scale (EDSS) call into question the reliability of the EDSS itself, according to researchers.

Preferred walking speed, for example, may vary by as much as 20% among patients with the same EDSS score. “Even though it is considered a walking scale, your scale defined groups of homogeneous disability are not even homogeneous for quantified measurement of walking ability,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y. “That’s a problem.”

Dr. Gudesblatt’s study was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

John F. Kurtzke, MD, developed the EDSS in 1967. The scale has become a standard outcome of clinical trials, alongside MRI measures and annualized relapse rates. More than 15 therapies for MS have received regulatory approval in part based on their effects on EDSS outcomes. Furthermore, the recently proposed treatment goal of no evidence of disease activity includes the EDSS among its criteria.

Functional ability, however, which the EDSS measures, depends on various factors such as cognitive function, manual dexterity, and ambulation. If the degree of variability of these factors is greater than 20% within groups defined as having similar disability, this scale would no longer be valid, according to Dr. Gudesblatt.

To analyze the variability in functional performance in groups of patients with similar disability, Dr. Gudesblatt and colleagues retrospectively reviewed data from a prospective MS registry. Participants underwent multidimensional computerized cognitive testing and digital gait analysis. They also submitted patient-reported outcomes for hand function while undergoing simultaneous measurements of Patient-Determined Disease Steps (PDDS) or EDSS. For the analysis, Dr. Gudesblatt and colleagues defined groups of “adjacent” EDSS scores as follows: from 0 to 2.5, from 3 to 4.5, from 5 to 6.5, and greater than 7.

In all, 258 patients with MS underwent cognitive testing. Of this group, 73% of patients were women, and mean age was 46 years. The proportion of overlap in multidomain computerized cognitive testing global summary score of 7 domains among patients with adjacent EDSS scores was 65%. The researchers found 42% overlap among patients at the extremes of the EDSS scale. The proportion of overlap in accumulative cognitive impairment (i.e., the number of cognitive domains impaired by greater than one standard deviation) was 72% across adjacent EDSS groups and 38% across extreme EDSS groups.

Among 254 patients with MS who underwent evaluation of walking, 72% were women, and mean age was 46 years. The mean normalized velocity of preferred walking speed varied by more than 20% within EDSS groups and overlapped by more than 20% between groups.

A total of 783 patients underwent evaluation of hand function and tremor. About 74% of these participants were women, and mean age was 49 years. The variability across all PDDS groups (i.e., 0 to 1, 2 to 4, and greater than 4) was greater than 50%. Adjacent PDDS groups had overlap of more than 50%, and the extremes had an overlap of greater than 32%.

“The criteria for the diagnosis [of MS] have undergone multiple revisions, but the scale to define the disability remains unchanged,” said Dr. Gudesblatt. “It’s all about trying to do the right thing for the right patient at the right time for the right reason. We cannot go by our own perceptions. You need to have objective not subjective information to appropriately improve measurements of disease trajectory. The neurologist must move beyond the hammer and tuning fork, must move to objective, quantitative, examiner-independent, multidimensional measures of important aspects of disease to enhance identification of critical disease impact along a continuum so as to improved shared decision making with patient centric objective data to improve outcomes and reduce disability.”

Dr. Gudesblatt has served on speakers bureaus for Acorda, Amgen, Medtronic, and Saol Therapeutics. He has performed contracted research for Biogen, EMD Serono, Novartis, Sanofi, and Teva. The study was conducted without external funding.

[email protected]

SOURCE: Gudesblatt M et al. CMSC 2020. Abstract QOL15.

The variability in functional performance within and between levels of disability measured by the Expanded Disability Status Scale (EDSS) call into question the reliability of the EDSS itself, according to researchers.

Preferred walking speed, for example, may vary by as much as 20% among patients with the same EDSS score. “Even though it is considered a walking scale, your scale defined groups of homogeneous disability are not even homogeneous for quantified measurement of walking ability,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y. “That’s a problem.”

Dr. Gudesblatt’s study was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

John F. Kurtzke, MD, developed the EDSS in 1967. The scale has become a standard outcome of clinical trials, alongside MRI measures and annualized relapse rates. More than 15 therapies for MS have received regulatory approval in part based on their effects on EDSS outcomes. Furthermore, the recently proposed treatment goal of no evidence of disease activity includes the EDSS among its criteria.

Functional ability, however, which the EDSS measures, depends on various factors such as cognitive function, manual dexterity, and ambulation. If the degree of variability of these factors is greater than 20% within groups defined as having similar disability, this scale would no longer be valid, according to Dr. Gudesblatt.

To analyze the variability in functional performance in groups of patients with similar disability, Dr. Gudesblatt and colleagues retrospectively reviewed data from a prospective MS registry. Participants underwent multidimensional computerized cognitive testing and digital gait analysis. They also submitted patient-reported outcomes for hand function while undergoing simultaneous measurements of Patient-Determined Disease Steps (PDDS) or EDSS. For the analysis, Dr. Gudesblatt and colleagues defined groups of “adjacent” EDSS scores as follows: from 0 to 2.5, from 3 to 4.5, from 5 to 6.5, and greater than 7.

In all, 258 patients with MS underwent cognitive testing. Of this group, 73% of patients were women, and mean age was 46 years. The proportion of overlap in multidomain computerized cognitive testing global summary score of 7 domains among patients with adjacent EDSS scores was 65%. The researchers found 42% overlap among patients at the extremes of the EDSS scale. The proportion of overlap in accumulative cognitive impairment (i.e., the number of cognitive domains impaired by greater than one standard deviation) was 72% across adjacent EDSS groups and 38% across extreme EDSS groups.

Among 254 patients with MS who underwent evaluation of walking, 72% were women, and mean age was 46 years. The mean normalized velocity of preferred walking speed varied by more than 20% within EDSS groups and overlapped by more than 20% between groups.

A total of 783 patients underwent evaluation of hand function and tremor. About 74% of these participants were women, and mean age was 49 years. The variability across all PDDS groups (i.e., 0 to 1, 2 to 4, and greater than 4) was greater than 50%. Adjacent PDDS groups had overlap of more than 50%, and the extremes had an overlap of greater than 32%.

“The criteria for the diagnosis [of MS] have undergone multiple revisions, but the scale to define the disability remains unchanged,” said Dr. Gudesblatt. “It’s all about trying to do the right thing for the right patient at the right time for the right reason. We cannot go by our own perceptions. You need to have objective not subjective information to appropriately improve measurements of disease trajectory. The neurologist must move beyond the hammer and tuning fork, must move to objective, quantitative, examiner-independent, multidimensional measures of important aspects of disease to enhance identification of critical disease impact along a continuum so as to improved shared decision making with patient centric objective data to improve outcomes and reduce disability.”

Dr. Gudesblatt has served on speakers bureaus for Acorda, Amgen, Medtronic, and Saol Therapeutics. He has performed contracted research for Biogen, EMD Serono, Novartis, Sanofi, and Teva. The study was conducted without external funding.

[email protected]

SOURCE: Gudesblatt M et al. CMSC 2020. Abstract QOL15.

The variability in functional performance within and between levels of disability measured by the Expanded Disability Status Scale (EDSS) call into question the reliability of the EDSS itself, according to researchers.

Preferred walking speed, for example, may vary by as much as 20% among patients with the same EDSS score. “Even though it is considered a walking scale, your scale defined groups of homogeneous disability are not even homogeneous for quantified measurement of walking ability,” said Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, N.Y. “That’s a problem.”

Dr. Gudesblatt’s study was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

John F. Kurtzke, MD, developed the EDSS in 1967. The scale has become a standard outcome of clinical trials, alongside MRI measures and annualized relapse rates. More than 15 therapies for MS have received regulatory approval in part based on their effects on EDSS outcomes. Furthermore, the recently proposed treatment goal of no evidence of disease activity includes the EDSS among its criteria.

Functional ability, however, which the EDSS measures, depends on various factors such as cognitive function, manual dexterity, and ambulation. If the degree of variability of these factors is greater than 20% within groups defined as having similar disability, this scale would no longer be valid, according to Dr. Gudesblatt.

To analyze the variability in functional performance in groups of patients with similar disability, Dr. Gudesblatt and colleagues retrospectively reviewed data from a prospective MS registry. Participants underwent multidimensional computerized cognitive testing and digital gait analysis. They also submitted patient-reported outcomes for hand function while undergoing simultaneous measurements of Patient-Determined Disease Steps (PDDS) or EDSS. For the analysis, Dr. Gudesblatt and colleagues defined groups of “adjacent” EDSS scores as follows: from 0 to 2.5, from 3 to 4.5, from 5 to 6.5, and greater than 7.

In all, 258 patients with MS underwent cognitive testing. Of this group, 73% of patients were women, and mean age was 46 years. The proportion of overlap in multidomain computerized cognitive testing global summary score of 7 domains among patients with adjacent EDSS scores was 65%. The researchers found 42% overlap among patients at the extremes of the EDSS scale. The proportion of overlap in accumulative cognitive impairment (i.e., the number of cognitive domains impaired by greater than one standard deviation) was 72% across adjacent EDSS groups and 38% across extreme EDSS groups.

Among 254 patients with MS who underwent evaluation of walking, 72% were women, and mean age was 46 years. The mean normalized velocity of preferred walking speed varied by more than 20% within EDSS groups and overlapped by more than 20% between groups.

A total of 783 patients underwent evaluation of hand function and tremor. About 74% of these participants were women, and mean age was 49 years. The variability across all PDDS groups (i.e., 0 to 1, 2 to 4, and greater than 4) was greater than 50%. Adjacent PDDS groups had overlap of more than 50%, and the extremes had an overlap of greater than 32%.

“The criteria for the diagnosis [of MS] have undergone multiple revisions, but the scale to define the disability remains unchanged,” said Dr. Gudesblatt. “It’s all about trying to do the right thing for the right patient at the right time for the right reason. We cannot go by our own perceptions. You need to have objective not subjective information to appropriately improve measurements of disease trajectory. The neurologist must move beyond the hammer and tuning fork, must move to objective, quantitative, examiner-independent, multidimensional measures of important aspects of disease to enhance identification of critical disease impact along a continuum so as to improved shared decision making with patient centric objective data to improve outcomes and reduce disability.”

Dr. Gudesblatt has served on speakers bureaus for Acorda, Amgen, Medtronic, and Saol Therapeutics. He has performed contracted research for Biogen, EMD Serono, Novartis, Sanofi, and Teva. The study was conducted without external funding.

[email protected]

SOURCE: Gudesblatt M et al. CMSC 2020. Abstract QOL15.

Key clinical point: Patients with relapsing-remitting multiple sclerosis (RRMS) having poor prognostic factors at baseline who were initiated with induction therapy have a lower risk for disability in the long term.

Major finding: After propensity matching, the proportion of patients reaching the primary outcome (Expanded Disability Status Scale [EDSS], ≥6.0) was lower in the induction group (28.0%) than the escalation group (38.7%). The median final EDSS scores were 5.0 and 4.5 after escalation and induction, respectively (P less than .001).

Study details: This study evaluated the long-term effectiveness of initial treatment with induction (n=75) or escalation (n=738) approach in patients with RRMS identified from a multicenter, retrospective registry database in Italy.

Disclosures: The authors declared no conflicts of interest.

Citation: Prosperini et al. Neurotherapeutics. 2020 Mar 31. doi: 10.1007/s13311-020-00847-0.

Key clinical point: Patients with relapsing-remitting multiple sclerosis (RRMS) having poor prognostic factors at baseline who were initiated with induction therapy have a lower risk for disability in the long term.

Major finding: After propensity matching, the proportion of patients reaching the primary outcome (Expanded Disability Status Scale [EDSS], ≥6.0) was lower in the induction group (28.0%) than the escalation group (38.7%). The median final EDSS scores were 5.0 and 4.5 after escalation and induction, respectively (P less than .001).

Study details: This study evaluated the long-term effectiveness of initial treatment with induction (n=75) or escalation (n=738) approach in patients with RRMS identified from a multicenter, retrospective registry database in Italy.

Disclosures: The authors declared no conflicts of interest.

Citation: Prosperini et al. Neurotherapeutics. 2020 Mar 31. doi: 10.1007/s13311-020-00847-0.

Key clinical point: Patients with relapsing-remitting multiple sclerosis (RRMS) having poor prognostic factors at baseline who were initiated with induction therapy have a lower risk for disability in the long term.

Major finding: After propensity matching, the proportion of patients reaching the primary outcome (Expanded Disability Status Scale [EDSS], ≥6.0) was lower in the induction group (28.0%) than the escalation group (38.7%). The median final EDSS scores were 5.0 and 4.5 after escalation and induction, respectively (P less than .001).

Study details: This study evaluated the long-term effectiveness of initial treatment with induction (n=75) or escalation (n=738) approach in patients with RRMS identified from a multicenter, retrospective registry database in Italy.

Disclosures: The authors declared no conflicts of interest.

Citation: Prosperini et al. Neurotherapeutics. 2020 Mar 31. doi: 10.1007/s13311-020-00847-0.

Key clinical point: A pro-inflammatory diet characterized by higher dietary inflammatory index (DII) and energy-adjusted DII (E-DII) during adolescence is a significant risk factor for the onset of multiple sclerosis (MS).

Major finding: The risks for MS increased significantly when E-DII was used as a continuous variable (adjusted odds ratio [aOR], 1.53; P = .001) and categorical variable (fourth vs. first quartile: aOR, 7.01; P less than .001). A similar pattern was seen for DII as both continuous and categorical variables.

Study details: This large population-based incident case-control study conducted in Iran included 547 patients with incident MS and 1057 individuals from the general population.

Disclosures: Dr Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company planning to license the DII from the University of South Carolina to develop computer and mobile applications. Dr Shivappa is an employee of CHI.

Citation: Abdollahpour I et al. Clin Nutr. 2020 Mar 6. doi: 10.1016/j.clnu.2020.02.033.

Key clinical point: A pro-inflammatory diet characterized by higher dietary inflammatory index (DII) and energy-adjusted DII (E-DII) during adolescence is a significant risk factor for the onset of multiple sclerosis (MS).

Major finding: The risks for MS increased significantly when E-DII was used as a continuous variable (adjusted odds ratio [aOR], 1.53; P = .001) and categorical variable (fourth vs. first quartile: aOR, 7.01; P less than .001). A similar pattern was seen for DII as both continuous and categorical variables.

Study details: This large population-based incident case-control study conducted in Iran included 547 patients with incident MS and 1057 individuals from the general population.

Disclosures: Dr Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company planning to license the DII from the University of South Carolina to develop computer and mobile applications. Dr Shivappa is an employee of CHI.

Citation: Abdollahpour I et al. Clin Nutr. 2020 Mar 6. doi: 10.1016/j.clnu.2020.02.033.

Key clinical point: A pro-inflammatory diet characterized by higher dietary inflammatory index (DII) and energy-adjusted DII (E-DII) during adolescence is a significant risk factor for the onset of multiple sclerosis (MS).

Major finding: The risks for MS increased significantly when E-DII was used as a continuous variable (adjusted odds ratio [aOR], 1.53; P = .001) and categorical variable (fourth vs. first quartile: aOR, 7.01; P less than .001). A similar pattern was seen for DII as both continuous and categorical variables.

Study details: This large population-based incident case-control study conducted in Iran included 547 patients with incident MS and 1057 individuals from the general population.

Disclosures: Dr Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company planning to license the DII from the University of South Carolina to develop computer and mobile applications. Dr Shivappa is an employee of CHI.

Citation: Abdollahpour I et al. Clin Nutr. 2020 Mar 6. doi: 10.1016/j.clnu.2020.02.033.

Key clinical point: In patients with multiple sclerosis (MS), protein concentrations of inflammatory cytokines, interleukin (IL)-27, transforming growth factor beta-1 (TGF-β1), and IL-10 are upregulated after 8 weeks of vitamin D₃ supplementation.

Major finding: In patients with MS, 8 weeks of vitamin D₃ administration upregulated the levels of IL-27 (P = .001), TGF-β1 (P less than .001), and IL-10 (P less than .001), whereas levels of IL-17A (P = .024) and IL-6 (P less than .001) were downregulated.

Study details: The study assessed venous blood samples drawn from individuals with MS (n=25) and control participants including first-degree relative (n=25) and healthy participants (n=25) before and after vitamin D₃ supplementation of 50,000 IU.

Disclosures: Dr SR Arefhosseini received financial support from Nutrition Research Center and Tabriz University of Medical Sciences, Tabriz, Iran.

Citation: Hashemi R et al. PLoS One. 2020 Apr 6. doi: 10.1371/journal.pone.0231145.

Key clinical point: In patients with multiple sclerosis (MS), protein concentrations of inflammatory cytokines, interleukin (IL)-27, transforming growth factor beta-1 (TGF-β1), and IL-10 are upregulated after 8 weeks of vitamin D₃ supplementation.

Major finding: In patients with MS, 8 weeks of vitamin D₃ administration upregulated the levels of IL-27 (P = .001), TGF-β1 (P less than .001), and IL-10 (P less than .001), whereas levels of IL-17A (P = .024) and IL-6 (P less than .001) were downregulated.

Study details: The study assessed venous blood samples drawn from individuals with MS (n=25) and control participants including first-degree relative (n=25) and healthy participants (n=25) before and after vitamin D₃ supplementation of 50,000 IU.

Disclosures: Dr SR Arefhosseini received financial support from Nutrition Research Center and Tabriz University of Medical Sciences, Tabriz, Iran.

Citation: Hashemi R et al. PLoS One. 2020 Apr 6. doi: 10.1371/journal.pone.0231145.

Key clinical point: In patients with multiple sclerosis (MS), protein concentrations of inflammatory cytokines, interleukin (IL)-27, transforming growth factor beta-1 (TGF-β1), and IL-10 are upregulated after 8 weeks of vitamin D₃ supplementation.

Major finding: In patients with MS, 8 weeks of vitamin D₃ administration upregulated the levels of IL-27 (P = .001), TGF-β1 (P less than .001), and IL-10 (P less than .001), whereas levels of IL-17A (P = .024) and IL-6 (P less than .001) were downregulated.

Study details: The study assessed venous blood samples drawn from individuals with MS (n=25) and control participants including first-degree relative (n=25) and healthy participants (n=25) before and after vitamin D₃ supplementation of 50,000 IU.

Disclosures: Dr SR Arefhosseini received financial support from Nutrition Research Center and Tabriz University of Medical Sciences, Tabriz, Iran.

Citation: Hashemi R et al. PLoS One. 2020 Apr 6. doi: 10.1371/journal.pone.0231145.

Key clinical point: Study finds direct evidence of transient neurotoxicity immediately after immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for aggressive multiple sclerosis (MS).

Major finding: Three months post-IAHSCT, levels of serum markers of both neuroaxonal and glial cell injury (serum Neurofilament Light Chain [sNfL] and serum Glial Fibrillary Acidic Protein [sGFAP]) increased from baseline by 32.1% (P = .029) and 74.8% (P = .0004), respectively. sNfL increases correlated with the dose of busulfan administered during transplant conditioning (P = .034), Expanded Disability Status Scale score (P = .041), as well as brain volume loss (P = .044), attributed to gray matter loss (P = .0023).

Study details: sNfL and sGFAP levels were evaluated pre- and post-IAHSCT at 3, 6, 9, and 12 months in 22 patients with MS and 28 noninflammatory control participants.

Disclosures: The study was funded by the MS Society of Canada. The authors declared no conflict of interest.

Citation: Thebault S et al. Ann Clin Transl Neurol. 2020 Apr 18. doi: 10.1002/acn3.51045.

Key clinical point: Study finds direct evidence of transient neurotoxicity immediately after immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for aggressive multiple sclerosis (MS).

Major finding: Three months post-IAHSCT, levels of serum markers of both neuroaxonal and glial cell injury (serum Neurofilament Light Chain [sNfL] and serum Glial Fibrillary Acidic Protein [sGFAP]) increased from baseline by 32.1% (P = .029) and 74.8% (P = .0004), respectively. sNfL increases correlated with the dose of busulfan administered during transplant conditioning (P = .034), Expanded Disability Status Scale score (P = .041), as well as brain volume loss (P = .044), attributed to gray matter loss (P = .0023).

Study details: sNfL and sGFAP levels were evaluated pre- and post-IAHSCT at 3, 6, 9, and 12 months in 22 patients with MS and 28 noninflammatory control participants.

Disclosures: The study was funded by the MS Society of Canada. The authors declared no conflict of interest.

Citation: Thebault S et al. Ann Clin Transl Neurol. 2020 Apr 18. doi: 10.1002/acn3.51045.

Key clinical point: Study finds direct evidence of transient neurotoxicity immediately after immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for aggressive multiple sclerosis (MS).

Major finding: Three months post-IAHSCT, levels of serum markers of both neuroaxonal and glial cell injury (serum Neurofilament Light Chain [sNfL] and serum Glial Fibrillary Acidic Protein [sGFAP]) increased from baseline by 32.1% (P = .029) and 74.8% (P = .0004), respectively. sNfL increases correlated with the dose of busulfan administered during transplant conditioning (P = .034), Expanded Disability Status Scale score (P = .041), as well as brain volume loss (P = .044), attributed to gray matter loss (P = .0023).

Study details: sNfL and sGFAP levels were evaluated pre- and post-IAHSCT at 3, 6, 9, and 12 months in 22 patients with MS and 28 noninflammatory control participants.

Disclosures: The study was funded by the MS Society of Canada. The authors declared no conflict of interest.

Citation: Thebault S et al. Ann Clin Transl Neurol. 2020 Apr 18. doi: 10.1002/acn3.51045.

Reports of herpes zoster virus (HZV) among patients being treated with disease-modifying therapies (DMTs) for multiple sclerosis (MS) are nearly five times higher among women versus men and commonly occur in people under the age of 40, a new study of adverse event reports on a variety of DMTs suggests.

DMTs are known to be associated with a potentially increased risk of opportunistic infections, including HZV. However, data are lacking on issues such as the relative frequency of HZV and the distribution of cases among age and gender groups, said senior author Ahmed Zayed Obeidat, MD, PhD, assistant professor at the Medical College of Wisconsin, Milwaukee.

“In my practice, we noticed patients being treated with DMTs were developing shingles at much younger ages than would be typical, so we were interested in looking at the distribution of cases among people treated with DMTs,” he said.

For the study, which was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers, Dr. Obeidat, first author Nicola Carlisle, MD, also of the Medical College of Wisconsin, and their colleagues turned to data from the Food and Drug Administration’s Adverse Event Reporting System.

They analyzed reports on adverse events involving HZV and varicella among patients with MS received between January 1999 and June 2019. The reports involved a range of MS DMTs, including interferon-beta, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, or ocrelizumab. Recently approved DMTs including cladribine and siponimod were excluded because of an insufficient number of reports.

Among 3,335 reports that were identified, they found highest mean annual report rates of HZV were for natalizumab, at 115.4, and lowest for glatiramer acetate, with just 5.3 reports. The mean annual report rates for HZV among the other DMTs were ocrelizumab, 88.3; dimethyl fumarate, 73.4; fingolimod, 72.9; interferon beta, 32.9; alemtuzumab, 21.7; and teriflunomide, 13.9.

Overall, the reports of HZV were 4.5 times more common among females, ranging from 2.1 times greater with alemtuzumab to 11.4 times greater for females with interferon-beta. The highest percentages of reports involved people in their 50s, with the exceptions of fingolimod, which had the highest rate of reports among patients in their 40s, and alemtuzumab, in which the highest percentage of reports involved patients in their 30s.

Meanwhile, as many as 25.7% of cases occurred in people under the age of 40 years, while 77.6% of total reports of HZV were in age groups between 31 years and 60 years.

“These rates are different than what is expected in the shingles population, which usually involves people over 60,” Dr. Obeidat said. He noted that, while MS is known to affect more women than men, the fivefold increase in HZV well exceeds the female-male ratio in MS, which is about 2.5:1.

Dr. Obeidat speculated that one factor explaining the higher reports of younger patients could be that fewer older patients are taking DMTs. “Many of our patients with MS may not be treated with DMTs when they are older or they may be on older DMTs that don’t have as much of a risk of opportunistic infections or activation, or some older patients may not be on medications anymore, so this may be why we are seeing this,” he said.

In commenting on the study, Joshua Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, Mass., speculated that numerous factors could explain the higher rates of women developing HZV.

“One wonders, for instance, did pregnancy play a role, were some of the women on prior medications?”

The statistical difference is interesting, he said, “but it’s hard to see what the explanation could be.”

While DMTs typically can be effective in suppressing an MS flare even if a patient develops shingles, the risks of the shingles, itself, is a concern, Dr. Katz added. “Just about any infection that stimulates an inflammatory response has some risk of worsening symptoms with MS; however, the bigger risk is probably the shingles itself and getting postherpetic neuralgia,” he explained.

“Sometimes there can be independent neurological problems just from MS, and that’s probably a bigger risk than worsening the MS,” he said. Clinicians should therefore keep shingles on their radar before starting patients on DMTs, Dr. Katz added.

“For many of the medications that are immunosuppressive, you want to check patients’ baseline levels of antibodies for zoster and if they don’t have antibodies, then you do want to vaccinate them.”

He noted that the new HZV vaccine is not a live vaccine and has a high efficacy rate, “so we think we can safely administer it in most cases.

“A concern is whether some DMTs may render the vaccine less effective, and we are looking at studying that with ocrelizumab and maybe some other B-cell depleting treatments.”

Dr. Obeidat disclosed relationships with Alexion, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Genentech, Sanofi and Novartis. Dr. Katz has been a speaker for Biogen, Genetech, Sanofi, and EMD Serono.

This article first appeared on Medscape.com.

Reports of herpes zoster virus (HZV) among patients being treated with disease-modifying therapies (DMTs) for multiple sclerosis (MS) are nearly five times higher among women versus men and commonly occur in people under the age of 40, a new study of adverse event reports on a variety of DMTs suggests.

DMTs are known to be associated with a potentially increased risk of opportunistic infections, including HZV. However, data are lacking on issues such as the relative frequency of HZV and the distribution of cases among age and gender groups, said senior author Ahmed Zayed Obeidat, MD, PhD, assistant professor at the Medical College of Wisconsin, Milwaukee.

“In my practice, we noticed patients being treated with DMTs were developing shingles at much younger ages than would be typical, so we were interested in looking at the distribution of cases among people treated with DMTs,” he said.

For the study, which was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers, Dr. Obeidat, first author Nicola Carlisle, MD, also of the Medical College of Wisconsin, and their colleagues turned to data from the Food and Drug Administration’s Adverse Event Reporting System.

They analyzed reports on adverse events involving HZV and varicella among patients with MS received between January 1999 and June 2019. The reports involved a range of MS DMTs, including interferon-beta, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, or ocrelizumab. Recently approved DMTs including cladribine and siponimod were excluded because of an insufficient number of reports.

Among 3,335 reports that were identified, they found highest mean annual report rates of HZV were for natalizumab, at 115.4, and lowest for glatiramer acetate, with just 5.3 reports. The mean annual report rates for HZV among the other DMTs were ocrelizumab, 88.3; dimethyl fumarate, 73.4; fingolimod, 72.9; interferon beta, 32.9; alemtuzumab, 21.7; and teriflunomide, 13.9.

Overall, the reports of HZV were 4.5 times more common among females, ranging from 2.1 times greater with alemtuzumab to 11.4 times greater for females with interferon-beta. The highest percentages of reports involved people in their 50s, with the exceptions of fingolimod, which had the highest rate of reports among patients in their 40s, and alemtuzumab, in which the highest percentage of reports involved patients in their 30s.

Meanwhile, as many as 25.7% of cases occurred in people under the age of 40 years, while 77.6% of total reports of HZV were in age groups between 31 years and 60 years.

“These rates are different than what is expected in the shingles population, which usually involves people over 60,” Dr. Obeidat said. He noted that, while MS is known to affect more women than men, the fivefold increase in HZV well exceeds the female-male ratio in MS, which is about 2.5:1.

Dr. Obeidat speculated that one factor explaining the higher reports of younger patients could be that fewer older patients are taking DMTs. “Many of our patients with MS may not be treated with DMTs when they are older or they may be on older DMTs that don’t have as much of a risk of opportunistic infections or activation, or some older patients may not be on medications anymore, so this may be why we are seeing this,” he said.

In commenting on the study, Joshua Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, Mass., speculated that numerous factors could explain the higher rates of women developing HZV.

“One wonders, for instance, did pregnancy play a role, were some of the women on prior medications?”

The statistical difference is interesting, he said, “but it’s hard to see what the explanation could be.”

While DMTs typically can be effective in suppressing an MS flare even if a patient develops shingles, the risks of the shingles, itself, is a concern, Dr. Katz added. “Just about any infection that stimulates an inflammatory response has some risk of worsening symptoms with MS; however, the bigger risk is probably the shingles itself and getting postherpetic neuralgia,” he explained.

“Sometimes there can be independent neurological problems just from MS, and that’s probably a bigger risk than worsening the MS,” he said. Clinicians should therefore keep shingles on their radar before starting patients on DMTs, Dr. Katz added.

“For many of the medications that are immunosuppressive, you want to check patients’ baseline levels of antibodies for zoster and if they don’t have antibodies, then you do want to vaccinate them.”

He noted that the new HZV vaccine is not a live vaccine and has a high efficacy rate, “so we think we can safely administer it in most cases.

“A concern is whether some DMTs may render the vaccine less effective, and we are looking at studying that with ocrelizumab and maybe some other B-cell depleting treatments.”

Dr. Obeidat disclosed relationships with Alexion, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Genentech, Sanofi and Novartis. Dr. Katz has been a speaker for Biogen, Genetech, Sanofi, and EMD Serono.

This article first appeared on Medscape.com.

Reports of herpes zoster virus (HZV) among patients being treated with disease-modifying therapies (DMTs) for multiple sclerosis (MS) are nearly five times higher among women versus men and commonly occur in people under the age of 40, a new study of adverse event reports on a variety of DMTs suggests.

DMTs are known to be associated with a potentially increased risk of opportunistic infections, including HZV. However, data are lacking on issues such as the relative frequency of HZV and the distribution of cases among age and gender groups, said senior author Ahmed Zayed Obeidat, MD, PhD, assistant professor at the Medical College of Wisconsin, Milwaukee.

“In my practice, we noticed patients being treated with DMTs were developing shingles at much younger ages than would be typical, so we were interested in looking at the distribution of cases among people treated with DMTs,” he said.

For the study, which was presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers, Dr. Obeidat, first author Nicola Carlisle, MD, also of the Medical College of Wisconsin, and their colleagues turned to data from the Food and Drug Administration’s Adverse Event Reporting System.

They analyzed reports on adverse events involving HZV and varicella among patients with MS received between January 1999 and June 2019. The reports involved a range of MS DMTs, including interferon-beta, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, or ocrelizumab. Recently approved DMTs including cladribine and siponimod were excluded because of an insufficient number of reports.

Among 3,335 reports that were identified, they found highest mean annual report rates of HZV were for natalizumab, at 115.4, and lowest for glatiramer acetate, with just 5.3 reports. The mean annual report rates for HZV among the other DMTs were ocrelizumab, 88.3; dimethyl fumarate, 73.4; fingolimod, 72.9; interferon beta, 32.9; alemtuzumab, 21.7; and teriflunomide, 13.9.

Overall, the reports of HZV were 4.5 times more common among females, ranging from 2.1 times greater with alemtuzumab to 11.4 times greater for females with interferon-beta. The highest percentages of reports involved people in their 50s, with the exceptions of fingolimod, which had the highest rate of reports among patients in their 40s, and alemtuzumab, in which the highest percentage of reports involved patients in their 30s.

Meanwhile, as many as 25.7% of cases occurred in people under the age of 40 years, while 77.6% of total reports of HZV were in age groups between 31 years and 60 years.

“These rates are different than what is expected in the shingles population, which usually involves people over 60,” Dr. Obeidat said. He noted that, while MS is known to affect more women than men, the fivefold increase in HZV well exceeds the female-male ratio in MS, which is about 2.5:1.

Dr. Obeidat speculated that one factor explaining the higher reports of younger patients could be that fewer older patients are taking DMTs. “Many of our patients with MS may not be treated with DMTs when they are older or they may be on older DMTs that don’t have as much of a risk of opportunistic infections or activation, or some older patients may not be on medications anymore, so this may be why we are seeing this,” he said.

In commenting on the study, Joshua Katz, MD, codirector of the Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, Mass., speculated that numerous factors could explain the higher rates of women developing HZV.

“One wonders, for instance, did pregnancy play a role, were some of the women on prior medications?”

The statistical difference is interesting, he said, “but it’s hard to see what the explanation could be.”

While DMTs typically can be effective in suppressing an MS flare even if a patient develops shingles, the risks of the shingles, itself, is a concern, Dr. Katz added. “Just about any infection that stimulates an inflammatory response has some risk of worsening symptoms with MS; however, the bigger risk is probably the shingles itself and getting postherpetic neuralgia,” he explained.

“Sometimes there can be independent neurological problems just from MS, and that’s probably a bigger risk than worsening the MS,” he said. Clinicians should therefore keep shingles on their radar before starting patients on DMTs, Dr. Katz added.

“For many of the medications that are immunosuppressive, you want to check patients’ baseline levels of antibodies for zoster and if they don’t have antibodies, then you do want to vaccinate them.”

He noted that the new HZV vaccine is not a live vaccine and has a high efficacy rate, “so we think we can safely administer it in most cases.

“A concern is whether some DMTs may render the vaccine less effective, and we are looking at studying that with ocrelizumab and maybe some other B-cell depleting treatments.”

Dr. Obeidat disclosed relationships with Alexion, Biogen, Bristol-Myers Squibb, Celgene, EMD Serono, Genentech, Sanofi and Novartis. Dr. Katz has been a speaker for Biogen, Genetech, Sanofi, and EMD Serono.

This article first appeared on Medscape.com.

The three oral disease-modifying therapies (DMTs) for multiple sclerosis (MS) approved last year in the United States haven’t made a big splash in the marketplace. So far, it’s more like a ripple, according to a study of neurologists’ prescribing patterns. “The recently approved therapies will initially be niched as later-line options,” predicted Virginia R. Schobel, MSc, nephrology franchise head at Spherix Global Insights, an independent market intelligence firm in Exton, Pa.

At the virtual annual meeting of the Consortium of Multiple Sclerosis Centers, Ms. Schobel presented the results of a retrospective chart audit Spherix conducted in February 2020 of 1,006 patients with MS who were switched to a new DMT by 199 U.S. participating neurologists within the previous 3 months. About 72% of the switchers had relapsing remitting MS (RRMS).
 

Assessing the three new oral DMTs

The purpose of the study was to gain an understanding of the early adoption patterns for the three recently approved oral DMTs: siponimod (Mayzent), cladribine (Mavenclad), and diroximel fumarate (Vumerity).

The first surprise was that only 41% of medication switches to a new DMT among the RRMS group were to oral DMTs; that’s a substantially lower proportion than in prior Spherix chart audits. Instead, the most popular switch was to ocrelizumab (Ocrevus), a monoclonal antibody.

“Things to keep in mind when we see the switch shares for the newer products are just how crowded this market has become and how much Ocrevus has really changed the market,” Ms. Schobel explained in an interview. “Ocrevus has become increasingly dominant in the RRMS segment, so that now there are six oral DMTs competing among themselves for a relatively limited pool of patients.”

Because of grandfathering by the Food and Drug Administration, most of the oral DMTs now share identical indications for clinically isolated syndrome, RRMS, and active secondary progressive MS. Ocrevus, she noted, has the same indications.

Only 1% of MS patients who switched to a different DMT in late 2019 or early 2020 moved to diroximel fumarate. Three percent switched to siponimod, and another 3% switched to cladribine. Switches to the three older, established oral DMTs were collectively five times more common, with 15% of patients moving to dimethyl fumarate (Tecfidera), 11% to fingolimod (Gilenya), and 9% to teriflunomide (Aubagio).

Ms. Schobel said that the three latest oral DMTs offer advantages over the older ones in terms of various combinations of efficacy, dosing schedule, and/or tolerability, which may make them attractive options as first-line therapy. She predicted that, over time as neurologists gain increasing familiarity with these drugs as first line, they will also gradually become more comfortable in turning to them as switch options.

First-time switches to an oral DMT among patients with RRMS were most often made in search of improved efficacy. Neurologists cited this as their main reason for 73% of switches to cladribine and 36% of switches to teriflunomide, with the other oral agents falling at various points in between. A switch to fingolimod was most often driven by a wish for a high-efficacy DMT with once-daily oral dosing. Improved tolerability figured prominently in switches to teriflunomide, and even more so in the relatively few changes to diroximel fumarate.
 

Drug switching in the pandemic era

Ms. Schobel said Spherix has been serially tracking neurologists’ prescribing for MS during the COVID-19 pandemic, which has clearly had an enormous dampening effect on medication switching. In mid-April, neurologists’ switching volume was down by 70%, compared with prepandemic figures. A slow recovery began in May, but by the end of the month prescription-switching volume was still down by 52%.

Of the neurologist prescriptions that are being run for switching thus far during the pandemic, 82% are being done via telemedicine. Therein hangs a tale, since neurology doesn’t readily lend itself to practice by telemedicine. Indeed, neurologists are using telemedicine to a lesser extent than physicians in the other specialties that Spherix monitors, according to Ms. Schobel. “COVID is definitely changing the MS world. Within MS, drug switching is now much more likely to involve a switch to a DMT that doesn’t impact the immune response and is not immunosuppressant, such as an injectable interferon or glatiramer acetate,” she said. “In this COVID world, safety and conservatism may end up trumping the move toward ‘time is brain’ which we’ve been talking so much about in recent years: the importance of getting patients on high-efficacy DMTs from the start in order to give them the best chance for positive outcomes.”

Ms. Schobel noted that Spherix received no industry funding to conduct these studies.

[email protected]

The three oral disease-modifying therapies (DMTs) for multiple sclerosis (MS) approved last year in the United States haven’t made a big splash in the marketplace. So far, it’s more like a ripple, according to a study of neurologists’ prescribing patterns. “The recently approved therapies will initially be niched as later-line options,” predicted Virginia R. Schobel, MSc, nephrology franchise head at Spherix Global Insights, an independent market intelligence firm in Exton, Pa.

At the virtual annual meeting of the Consortium of Multiple Sclerosis Centers, Ms. Schobel presented the results of a retrospective chart audit Spherix conducted in February 2020 of 1,006 patients with MS who were switched to a new DMT by 199 U.S. participating neurologists within the previous 3 months. About 72% of the switchers had relapsing remitting MS (RRMS).
 

Assessing the three new oral DMTs

The purpose of the study was to gain an understanding of the early adoption patterns for the three recently approved oral DMTs: siponimod (Mayzent), cladribine (Mavenclad), and diroximel fumarate (Vumerity).

The first surprise was that only 41% of medication switches to a new DMT among the RRMS group were to oral DMTs; that’s a substantially lower proportion than in prior Spherix chart audits. Instead, the most popular switch was to ocrelizumab (Ocrevus), a monoclonal antibody.

“Things to keep in mind when we see the switch shares for the newer products are just how crowded this market has become and how much Ocrevus has really changed the market,” Ms. Schobel explained in an interview. “Ocrevus has become increasingly dominant in the RRMS segment, so that now there are six oral DMTs competing among themselves for a relatively limited pool of patients.”

Because of grandfathering by the Food and Drug Administration, most of the oral DMTs now share identical indications for clinically isolated syndrome, RRMS, and active secondary progressive MS. Ocrevus, she noted, has the same indications.

Only 1% of MS patients who switched to a different DMT in late 2019 or early 2020 moved to diroximel fumarate. Three percent switched to siponimod, and another 3% switched to cladribine. Switches to the three older, established oral DMTs were collectively five times more common, with 15% of patients moving to dimethyl fumarate (Tecfidera), 11% to fingolimod (Gilenya), and 9% to teriflunomide (Aubagio).

Ms. Schobel said that the three latest oral DMTs offer advantages over the older ones in terms of various combinations of efficacy, dosing schedule, and/or tolerability, which may make them attractive options as first-line therapy. She predicted that, over time as neurologists gain increasing familiarity with these drugs as first line, they will also gradually become more comfortable in turning to them as switch options.

First-time switches to an oral DMT among patients with RRMS were most often made in search of improved efficacy. Neurologists cited this as their main reason for 73% of switches to cladribine and 36% of switches to teriflunomide, with the other oral agents falling at various points in between. A switch to fingolimod was most often driven by a wish for a high-efficacy DMT with once-daily oral dosing. Improved tolerability figured prominently in switches to teriflunomide, and even more so in the relatively few changes to diroximel fumarate.
 

Drug switching in the pandemic era

Ms. Schobel said Spherix has been serially tracking neurologists’ prescribing for MS during the COVID-19 pandemic, which has clearly had an enormous dampening effect on medication switching. In mid-April, neurologists’ switching volume was down by 70%, compared with prepandemic figures. A slow recovery began in May, but by the end of the month prescription-switching volume was still down by 52%.

Of the neurologist prescriptions that are being run for switching thus far during the pandemic, 82% are being done via telemedicine. Therein hangs a tale, since neurology doesn’t readily lend itself to practice by telemedicine. Indeed, neurologists are using telemedicine to a lesser extent than physicians in the other specialties that Spherix monitors, according to Ms. Schobel. “COVID is definitely changing the MS world. Within MS, drug switching is now much more likely to involve a switch to a DMT that doesn’t impact the immune response and is not immunosuppressant, such as an injectable interferon or glatiramer acetate,” she said. “In this COVID world, safety and conservatism may end up trumping the move toward ‘time is brain’ which we’ve been talking so much about in recent years: the importance of getting patients on high-efficacy DMTs from the start in order to give them the best chance for positive outcomes.”

Ms. Schobel noted that Spherix received no industry funding to conduct these studies.

[email protected]

The three oral disease-modifying therapies (DMTs) for multiple sclerosis (MS) approved last year in the United States haven’t made a big splash in the marketplace. So far, it’s more like a ripple, according to a study of neurologists’ prescribing patterns. “The recently approved therapies will initially be niched as later-line options,” predicted Virginia R. Schobel, MSc, nephrology franchise head at Spherix Global Insights, an independent market intelligence firm in Exton, Pa.

At the virtual annual meeting of the Consortium of Multiple Sclerosis Centers, Ms. Schobel presented the results of a retrospective chart audit Spherix conducted in February 2020 of 1,006 patients with MS who were switched to a new DMT by 199 U.S. participating neurologists within the previous 3 months. About 72% of the switchers had relapsing remitting MS (RRMS).
 

Assessing the three new oral DMTs

The purpose of the study was to gain an understanding of the early adoption patterns for the three recently approved oral DMTs: siponimod (Mayzent), cladribine (Mavenclad), and diroximel fumarate (Vumerity).

The first surprise was that only 41% of medication switches to a new DMT among the RRMS group were to oral DMTs; that’s a substantially lower proportion than in prior Spherix chart audits. Instead, the most popular switch was to ocrelizumab (Ocrevus), a monoclonal antibody.

“Things to keep in mind when we see the switch shares for the newer products are just how crowded this market has become and how much Ocrevus has really changed the market,” Ms. Schobel explained in an interview. “Ocrevus has become increasingly dominant in the RRMS segment, so that now there are six oral DMTs competing among themselves for a relatively limited pool of patients.”

Because of grandfathering by the Food and Drug Administration, most of the oral DMTs now share identical indications for clinically isolated syndrome, RRMS, and active secondary progressive MS. Ocrevus, she noted, has the same indications.

Only 1% of MS patients who switched to a different DMT in late 2019 or early 2020 moved to diroximel fumarate. Three percent switched to siponimod, and another 3% switched to cladribine. Switches to the three older, established oral DMTs were collectively five times more common, with 15% of patients moving to dimethyl fumarate (Tecfidera), 11% to fingolimod (Gilenya), and 9% to teriflunomide (Aubagio).

Ms. Schobel said that the three latest oral DMTs offer advantages over the older ones in terms of various combinations of efficacy, dosing schedule, and/or tolerability, which may make them attractive options as first-line therapy. She predicted that, over time as neurologists gain increasing familiarity with these drugs as first line, they will also gradually become more comfortable in turning to them as switch options.

First-time switches to an oral DMT among patients with RRMS were most often made in search of improved efficacy. Neurologists cited this as their main reason for 73% of switches to cladribine and 36% of switches to teriflunomide, with the other oral agents falling at various points in between. A switch to fingolimod was most often driven by a wish for a high-efficacy DMT with once-daily oral dosing. Improved tolerability figured prominently in switches to teriflunomide, and even more so in the relatively few changes to diroximel fumarate.
 

Drug switching in the pandemic era

Ms. Schobel said Spherix has been serially tracking neurologists’ prescribing for MS during the COVID-19 pandemic, which has clearly had an enormous dampening effect on medication switching. In mid-April, neurologists’ switching volume was down by 70%, compared with prepandemic figures. A slow recovery began in May, but by the end of the month prescription-switching volume was still down by 52%.

Of the neurologist prescriptions that are being run for switching thus far during the pandemic, 82% are being done via telemedicine. Therein hangs a tale, since neurology doesn’t readily lend itself to practice by telemedicine. Indeed, neurologists are using telemedicine to a lesser extent than physicians in the other specialties that Spherix monitors, according to Ms. Schobel. “COVID is definitely changing the MS world. Within MS, drug switching is now much more likely to involve a switch to a DMT that doesn’t impact the immune response and is not immunosuppressant, such as an injectable interferon or glatiramer acetate,” she said. “In this COVID world, safety and conservatism may end up trumping the move toward ‘time is brain’ which we’ve been talking so much about in recent years: the importance of getting patients on high-efficacy DMTs from the start in order to give them the best chance for positive outcomes.”

Ms. Schobel noted that Spherix received no industry funding to conduct these studies.

[email protected]