Multiple Sclerosis Hub

A new study has found that patients with multiple sclerosis (MS) who smoke cigarettes regularly have an increased risk of higher plasma neurofilament light levels (pNfL), which is associated with increased disease activity and reduced response to treatment. At the same time, patients who have stopped smoking have notably lower risk that correlates to how long ago they quit.

“Before, all the studies that were looking at the association between smoking and MS – especially in terms of severity – were using indications like the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score,” said first author Ali Manouchehrinia, PhD, assistant professor at the Karolinska Institute, Stockholm. “Now, we have NfL as a biomarker for disease activity, and we can see the effect of smoking on that biomarker.”

The ultimate goal, he added, “is to tease out the effects of MS severity and disease activity from NfL, to make sure that changes or differences in NfL levels are truly caused by MS and nothing else.”

Dr. Manouchehrinia presented his team’s findings at the virtual annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

To determine any associations between smoking and pNfL levels, the researchers began a retrospective, population-based cohort study of 2,572 Swedish MS patients with a self-reported history of cigarette smoking. Their average age was 38.2 years, slightly more than 71% were women, and their average disease duration was 4.13 years.

Blood samples were collected at each patients’ time of diagnosis to analyze concentrations of pNfL. Three age-stratified pNfL levels were classified: above the 80th (>C80), 95th (>C95), and 99th (>C99) of 1,026 non-MS controls’ percentiles.

Of the 2,572 MS patients, 292 (11.4%) were current regular smokers and 714 (27.8%) were past regular smokers. The past smokers’ median time since quitting was 2 years. Being a current smoker was associated with much higher odds of having pNfL levels at >C99, compared with never smokers (odds ratio, 1.52; 95% confidence interval, 1.12-2.05; P = .007) and past smokers (OR, 1.42; 95% CI, 1.01-1.99; P = .043).

For past smokers who quit between 6 and 10 years ago, the risk of having pNfL levels at >C99 was considerably lower (OR, 0.53; 95% CI, 0.29-0.93; P = .032), compared with current smokers, as was the risk for past smokers who quit more than 10 years ago (OR, 0.50; 95% CI, 0.29-0.84; P = .010). The odds were also lower, though not significantly, for patients who quit 1-5 years ago (OR, 0.84; 95% CI, 0.58-1.22; P = .359).

“It looks like, after 10 years, you go back to the baseline and have the same risk as the never smokers,” Dr. Manouchehrinia said. “But the damage may have already been done. Quitting smoking is good, but it’s better to not smoke at all.”

Dr. Manouchehrinia acknowledged the study’s limitations, including the need to learn more about the role NfL levels – especially plasma NfL levels – play across MS patients, along with the complications surrounding smoking as an environmental factor. He noted that, in Sweden, many people get their nicotine from snuff rather than cigarettes. “Among our MS population, we’ve seen a recent shift toward female snuff users,” which lessens the amount they smoke and could confound the results. In fact, the study indicated that snuff users had less risk of pNfL levels at >C95, compared with nonsnuff users (OR, 0.71; 95% CI, 0.51-0.97; P = .034).

The authors reported several potential conflicts of interest, including receiving research grants and lecture honoraria and serving on advisory boards for various pharmaceutical companies.

A new study has found that patients with multiple sclerosis (MS) who smoke cigarettes regularly have an increased risk of higher plasma neurofilament light levels (pNfL), which is associated with increased disease activity and reduced response to treatment. At the same time, patients who have stopped smoking have notably lower risk that correlates to how long ago they quit.

“Before, all the studies that were looking at the association between smoking and MS – especially in terms of severity – were using indications like the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score,” said first author Ali Manouchehrinia, PhD, assistant professor at the Karolinska Institute, Stockholm. “Now, we have NfL as a biomarker for disease activity, and we can see the effect of smoking on that biomarker.”

The ultimate goal, he added, “is to tease out the effects of MS severity and disease activity from NfL, to make sure that changes or differences in NfL levels are truly caused by MS and nothing else.”

Dr. Manouchehrinia presented his team’s findings at the virtual annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

To determine any associations between smoking and pNfL levels, the researchers began a retrospective, population-based cohort study of 2,572 Swedish MS patients with a self-reported history of cigarette smoking. Their average age was 38.2 years, slightly more than 71% were women, and their average disease duration was 4.13 years.

Blood samples were collected at each patients’ time of diagnosis to analyze concentrations of pNfL. Three age-stratified pNfL levels were classified: above the 80th (>C80), 95th (>C95), and 99th (>C99) of 1,026 non-MS controls’ percentiles.

Of the 2,572 MS patients, 292 (11.4%) were current regular smokers and 714 (27.8%) were past regular smokers. The past smokers’ median time since quitting was 2 years. Being a current smoker was associated with much higher odds of having pNfL levels at >C99, compared with never smokers (odds ratio, 1.52; 95% confidence interval, 1.12-2.05; P = .007) and past smokers (OR, 1.42; 95% CI, 1.01-1.99; P = .043).

For past smokers who quit between 6 and 10 years ago, the risk of having pNfL levels at >C99 was considerably lower (OR, 0.53; 95% CI, 0.29-0.93; P = .032), compared with current smokers, as was the risk for past smokers who quit more than 10 years ago (OR, 0.50; 95% CI, 0.29-0.84; P = .010). The odds were also lower, though not significantly, for patients who quit 1-5 years ago (OR, 0.84; 95% CI, 0.58-1.22; P = .359).

“It looks like, after 10 years, you go back to the baseline and have the same risk as the never smokers,” Dr. Manouchehrinia said. “But the damage may have already been done. Quitting smoking is good, but it’s better to not smoke at all.”

Dr. Manouchehrinia acknowledged the study’s limitations, including the need to learn more about the role NfL levels – especially plasma NfL levels – play across MS patients, along with the complications surrounding smoking as an environmental factor. He noted that, in Sweden, many people get their nicotine from snuff rather than cigarettes. “Among our MS population, we’ve seen a recent shift toward female snuff users,” which lessens the amount they smoke and could confound the results. In fact, the study indicated that snuff users had less risk of pNfL levels at >C95, compared with nonsnuff users (OR, 0.71; 95% CI, 0.51-0.97; P = .034).

The authors reported several potential conflicts of interest, including receiving research grants and lecture honoraria and serving on advisory boards for various pharmaceutical companies.

A new study has found that patients with multiple sclerosis (MS) who smoke cigarettes regularly have an increased risk of higher plasma neurofilament light levels (pNfL), which is associated with increased disease activity and reduced response to treatment. At the same time, patients who have stopped smoking have notably lower risk that correlates to how long ago they quit.

“Before, all the studies that were looking at the association between smoking and MS – especially in terms of severity – were using indications like the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score,” said first author Ali Manouchehrinia, PhD, assistant professor at the Karolinska Institute, Stockholm. “Now, we have NfL as a biomarker for disease activity, and we can see the effect of smoking on that biomarker.”

The ultimate goal, he added, “is to tease out the effects of MS severity and disease activity from NfL, to make sure that changes or differences in NfL levels are truly caused by MS and nothing else.”

Dr. Manouchehrinia presented his team’s findings at the virtual annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

To determine any associations between smoking and pNfL levels, the researchers began a retrospective, population-based cohort study of 2,572 Swedish MS patients with a self-reported history of cigarette smoking. Their average age was 38.2 years, slightly more than 71% were women, and their average disease duration was 4.13 years.

Blood samples were collected at each patients’ time of diagnosis to analyze concentrations of pNfL. Three age-stratified pNfL levels were classified: above the 80th (>C80), 95th (>C95), and 99th (>C99) of 1,026 non-MS controls’ percentiles.

Of the 2,572 MS patients, 292 (11.4%) were current regular smokers and 714 (27.8%) were past regular smokers. The past smokers’ median time since quitting was 2 years. Being a current smoker was associated with much higher odds of having pNfL levels at >C99, compared with never smokers (odds ratio, 1.52; 95% confidence interval, 1.12-2.05; P = .007) and past smokers (OR, 1.42; 95% CI, 1.01-1.99; P = .043).

For past smokers who quit between 6 and 10 years ago, the risk of having pNfL levels at >C99 was considerably lower (OR, 0.53; 95% CI, 0.29-0.93; P = .032), compared with current smokers, as was the risk for past smokers who quit more than 10 years ago (OR, 0.50; 95% CI, 0.29-0.84; P = .010). The odds were also lower, though not significantly, for patients who quit 1-5 years ago (OR, 0.84; 95% CI, 0.58-1.22; P = .359).

“It looks like, after 10 years, you go back to the baseline and have the same risk as the never smokers,” Dr. Manouchehrinia said. “But the damage may have already been done. Quitting smoking is good, but it’s better to not smoke at all.”

Dr. Manouchehrinia acknowledged the study’s limitations, including the need to learn more about the role NfL levels – especially plasma NfL levels – play across MS patients, along with the complications surrounding smoking as an environmental factor. He noted that, in Sweden, many people get their nicotine from snuff rather than cigarettes. “Among our MS population, we’ve seen a recent shift toward female snuff users,” which lessens the amount they smoke and could confound the results. In fact, the study indicated that snuff users had less risk of pNfL levels at >C95, compared with nonsnuff users (OR, 0.71; 95% CI, 0.51-0.97; P = .034).

The authors reported several potential conflicts of interest, including receiving research grants and lecture honoraria and serving on advisory boards for various pharmaceutical companies.

A new study has found that reducing rituximab dosage from 1,000 mg/6 months to 500 mg/6 months is a safe and stable choice for patients with multiple sclerosis (MS).

“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.

To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.

All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
 

Study results

All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).

During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).

A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
 

Validating clinical experience

“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”

Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.

“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”

The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”

The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.

SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.

A new study has found that reducing rituximab dosage from 1,000 mg/6 months to 500 mg/6 months is a safe and stable choice for patients with multiple sclerosis (MS).

“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.

To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.

All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
 

Study results

All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).

During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).

A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
 

Validating clinical experience

“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”

Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.

“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”

The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”

The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.

SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.

A new study has found that reducing rituximab dosage from 1,000 mg/6 months to 500 mg/6 months is a safe and stable choice for patients with multiple sclerosis (MS).

“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.

To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.

All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
 

Study results

All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).

During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).

A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
 

Validating clinical experience

“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”

Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.

“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”

The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”

The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.

SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.

The Food and Drug Administration has approved Kesimpta ofatumumab (Kesimpta) injection for the treatment of adults with relapsing forms of multiple sclerosis, including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.

“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.

Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.

Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.

Twin studies

Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.

The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.

As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.

The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.

Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).

The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.

Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.

The drug is expected to be available in the United States in September.

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

The Food and Drug Administration has approved Kesimpta ofatumumab (Kesimpta) injection for the treatment of adults with relapsing forms of multiple sclerosis, including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.

“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.

Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.

Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.

Twin studies

Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.

The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.

As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.

The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.

Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).

The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.

Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.

The drug is expected to be available in the United States in September.

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

The Food and Drug Administration has approved Kesimpta ofatumumab (Kesimpta) injection for the treatment of adults with relapsing forms of multiple sclerosis, including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.

“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.

Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.

Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.

Twin studies

Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.

The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.

As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.

The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.

Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).

The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.

Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.

The drug is expected to be available in the United States in September.

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

The efficacy of the influenza vaccine when given to patients with multiple sclerosis (MS) is similar to that in healthy controls, Jackie Nguyen reported at the virtual annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC). She presented a systematic review and meta-analysis of nine published cohort studies including 417 MS patients and more than 500 healthy controls, all of whom received inactivated seasonal influenza vaccine.

The impetus for this project was a recognition that the great majority of the research on the impact of influenza vaccine in patients with MS has focused on safety and MS relapse rates. In contrast, the nine studies included in the meta-analysis contained data on influenza vaccine efficacy as reflected in the ability to mount an adequate immune response. This was defined in standard fashion either by seroconversion, which required at least a fourfold increase in antibody titers following vaccination, or seroprotection, with a postvaccination antihemagglutination immunoglobulin G titer of at least 40. The analysis included patients with MS irrespective of disease duration or severity or treatment regimen, noted Ms. Nguyen, a third-year medical student at Nova Southeastern University College of Allopathic Medicine in Davie, Fla.

The researchers found that there was no significant difference between patients with MS and healthy controls in the rates of an adequate immune response for influenza H1N1, H3N2, or influenza B virus. “The vaccine should thus continue to be recommended for MS patients, as the data shows it to be efficacious,” she said.

Her conclusion is consistent with guidance provided in the American Academy of Neurology’s 2019 practice guideline update on immunization in MS, highlighted elsewhere at CMSC 2020 in a presentation by Marijean Buhse, PhD, of Stony Brook University in New York.

The guideline, updated for the first time in 17 years, states that all MS patients should be advised to receive influenza vaccine annually: “With known risks of exacerbation and other morbidity with influenza infection and no identified risks of exacerbation with influenza vaccines, benefits of influenza vaccination outweigh the risks in most scenarios. The exception involves the relatively few MS patients having a specific contraindication to the influenza vaccine, such as a previous severe reaction, noted Dr. Buhse, who wasn’t involved in developing the evidence-based guidelines.

The available evidence indicates that some but not all disease-modifying therapies for MS reduce the effectiveness of vaccination against influenza.

According to the guideline, “it is possible” that persons with MS being treated with glatiramer acetate have a reduced likelihood of seroprotection from influenza vaccine, a conclusion the guidelines committee drew with “low confidence in the evidence.” Further, the guideline states that “it is probable” MS patients on fingolimod have a lower likelihood of obtaining seroprotection from influenza vaccine than patients not on the drug, with moderate confidence in the evidence. Also, it is deemed probable that patients with MS who are taking mitoxantrone have a reduced likelihood of response to influenza vaccination, compared with healthy controls. But it is probable that patients with MS who are receiving interferon-beta have no diminution in the likelihood of seroprotection. According to the guideline, there is insufficient evidence to say whether patients with MS who are on natalizumab, teriflunomide, or methotrexate have a diminished response to influenza vaccination.

Dr. Buhse noted that rituximab is off-label therapy for MS, so there are no data available regarding the likelihood of seroprotection in response to influenza vaccination in that setting. However, rituximab profoundly decreases the immunogenicity of influenza and pneumococcal vaccines in rheumatoid arthritis patients. It is therefore recommended that inactivated influenza vaccine be given to patients with MS at least 2 weeks prior to starting rituximab or 6 months after the last dose in order to optimize the humoral results. Ms. Nguyen reported having no financial conflicts regarding her presentation. Dr. Buhse reported having received honoraria from Genzyme and Biogen.

[email protected]

The efficacy of the influenza vaccine when given to patients with multiple sclerosis (MS) is similar to that in healthy controls, Jackie Nguyen reported at the virtual annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC). She presented a systematic review and meta-analysis of nine published cohort studies including 417 MS patients and more than 500 healthy controls, all of whom received inactivated seasonal influenza vaccine.

The impetus for this project was a recognition that the great majority of the research on the impact of influenza vaccine in patients with MS has focused on safety and MS relapse rates. In contrast, the nine studies included in the meta-analysis contained data on influenza vaccine efficacy as reflected in the ability to mount an adequate immune response. This was defined in standard fashion either by seroconversion, which required at least a fourfold increase in antibody titers following vaccination, or seroprotection, with a postvaccination antihemagglutination immunoglobulin G titer of at least 40. The analysis included patients with MS irrespective of disease duration or severity or treatment regimen, noted Ms. Nguyen, a third-year medical student at Nova Southeastern University College of Allopathic Medicine in Davie, Fla.

The researchers found that there was no significant difference between patients with MS and healthy controls in the rates of an adequate immune response for influenza H1N1, H3N2, or influenza B virus. “The vaccine should thus continue to be recommended for MS patients, as the data shows it to be efficacious,” she said.

Her conclusion is consistent with guidance provided in the American Academy of Neurology’s 2019 practice guideline update on immunization in MS, highlighted elsewhere at CMSC 2020 in a presentation by Marijean Buhse, PhD, of Stony Brook University in New York.

The guideline, updated for the first time in 17 years, states that all MS patients should be advised to receive influenza vaccine annually: “With known risks of exacerbation and other morbidity with influenza infection and no identified risks of exacerbation with influenza vaccines, benefits of influenza vaccination outweigh the risks in most scenarios. The exception involves the relatively few MS patients having a specific contraindication to the influenza vaccine, such as a previous severe reaction, noted Dr. Buhse, who wasn’t involved in developing the evidence-based guidelines.

The available evidence indicates that some but not all disease-modifying therapies for MS reduce the effectiveness of vaccination against influenza.

According to the guideline, “it is possible” that persons with MS being treated with glatiramer acetate have a reduced likelihood of seroprotection from influenza vaccine, a conclusion the guidelines committee drew with “low confidence in the evidence.” Further, the guideline states that “it is probable” MS patients on fingolimod have a lower likelihood of obtaining seroprotection from influenza vaccine than patients not on the drug, with moderate confidence in the evidence. Also, it is deemed probable that patients with MS who are taking mitoxantrone have a reduced likelihood of response to influenza vaccination, compared with healthy controls. But it is probable that patients with MS who are receiving interferon-beta have no diminution in the likelihood of seroprotection. According to the guideline, there is insufficient evidence to say whether patients with MS who are on natalizumab, teriflunomide, or methotrexate have a diminished response to influenza vaccination.

Dr. Buhse noted that rituximab is off-label therapy for MS, so there are no data available regarding the likelihood of seroprotection in response to influenza vaccination in that setting. However, rituximab profoundly decreases the immunogenicity of influenza and pneumococcal vaccines in rheumatoid arthritis patients. It is therefore recommended that inactivated influenza vaccine be given to patients with MS at least 2 weeks prior to starting rituximab or 6 months after the last dose in order to optimize the humoral results. Ms. Nguyen reported having no financial conflicts regarding her presentation. Dr. Buhse reported having received honoraria from Genzyme and Biogen.

[email protected]

The efficacy of the influenza vaccine when given to patients with multiple sclerosis (MS) is similar to that in healthy controls, Jackie Nguyen reported at the virtual annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC). She presented a systematic review and meta-analysis of nine published cohort studies including 417 MS patients and more than 500 healthy controls, all of whom received inactivated seasonal influenza vaccine.

The impetus for this project was a recognition that the great majority of the research on the impact of influenza vaccine in patients with MS has focused on safety and MS relapse rates. In contrast, the nine studies included in the meta-analysis contained data on influenza vaccine efficacy as reflected in the ability to mount an adequate immune response. This was defined in standard fashion either by seroconversion, which required at least a fourfold increase in antibody titers following vaccination, or seroprotection, with a postvaccination antihemagglutination immunoglobulin G titer of at least 40. The analysis included patients with MS irrespective of disease duration or severity or treatment regimen, noted Ms. Nguyen, a third-year medical student at Nova Southeastern University College of Allopathic Medicine in Davie, Fla.

The researchers found that there was no significant difference between patients with MS and healthy controls in the rates of an adequate immune response for influenza H1N1, H3N2, or influenza B virus. “The vaccine should thus continue to be recommended for MS patients, as the data shows it to be efficacious,” she said.

Her conclusion is consistent with guidance provided in the American Academy of Neurology’s 2019 practice guideline update on immunization in MS, highlighted elsewhere at CMSC 2020 in a presentation by Marijean Buhse, PhD, of Stony Brook University in New York.

The guideline, updated for the first time in 17 years, states that all MS patients should be advised to receive influenza vaccine annually: “With known risks of exacerbation and other morbidity with influenza infection and no identified risks of exacerbation with influenza vaccines, benefits of influenza vaccination outweigh the risks in most scenarios. The exception involves the relatively few MS patients having a specific contraindication to the influenza vaccine, such as a previous severe reaction, noted Dr. Buhse, who wasn’t involved in developing the evidence-based guidelines.

The available evidence indicates that some but not all disease-modifying therapies for MS reduce the effectiveness of vaccination against influenza.

According to the guideline, “it is possible” that persons with MS being treated with glatiramer acetate have a reduced likelihood of seroprotection from influenza vaccine, a conclusion the guidelines committee drew with “low confidence in the evidence.” Further, the guideline states that “it is probable” MS patients on fingolimod have a lower likelihood of obtaining seroprotection from influenza vaccine than patients not on the drug, with moderate confidence in the evidence. Also, it is deemed probable that patients with MS who are taking mitoxantrone have a reduced likelihood of response to influenza vaccination, compared with healthy controls. But it is probable that patients with MS who are receiving interferon-beta have no diminution in the likelihood of seroprotection. According to the guideline, there is insufficient evidence to say whether patients with MS who are on natalizumab, teriflunomide, or methotrexate have a diminished response to influenza vaccination.

Dr. Buhse noted that rituximab is off-label therapy for MS, so there are no data available regarding the likelihood of seroprotection in response to influenza vaccination in that setting. However, rituximab profoundly decreases the immunogenicity of influenza and pneumococcal vaccines in rheumatoid arthritis patients. It is therefore recommended that inactivated influenza vaccine be given to patients with MS at least 2 weeks prior to starting rituximab or 6 months after the last dose in order to optimize the humoral results. Ms. Nguyen reported having no financial conflicts regarding her presentation. Dr. Buhse reported having received honoraria from Genzyme and Biogen.

[email protected]

Proposed updates to guidelines for magnetic resonance imaging in patients with multiple sclerosis (MS) are in the works to make the Consortium of Multiple Sclerosis Centers protocol and other international guidelines more similar, with the hope that internationally accepted consensus guidelines will improve lagging conformity with the recommendations.

“We’ve always envisioned the guidelines as being international, but now we have harmony with the groups, so this is truly a global protocol,” Anthony Traboulsee, MD, a professor of neurology and director of the MS clinic and neuromyelitis optica clinic at the University of British Columbia in Vancouver, said in presenting the proposed updates during the virtual meeting of the CMSC.

The updates reflect the input of an international expert panel convened by the CMSC in October 2019, made up of neurologists, radiologists, magnetic resonance technologists, and imaging scientists with expertise in MS. Attendees represented groups including the European-based Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, National MS Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis.
 

Standardizing scans

While the mission was to review and update the current guidelines, an important overriding objective was to boost universal acceptance and improve the utilization of the protocol, which research shows is surprisingly low. According to one poster presented at the meeting, a real-world MRI dataset of 1,233 sessions showed only 8% satisfied criteria for the T1 sequence outlined in the 2018 guidelines, and only 7% satisfied criteria for the T2 sequence. “In a real-world MRI dataset of patients with MS, the conformance to the CMSC brain MRI guidelines was extremely low,” concluded the authors, who were with Icometrix, in Chicago and Belgium.

David Li, MD, also of the University of British Columbia and cochair of the MRI guideline committee, said the nonconformity has important implications. “Nonstandardized scans, with inconsistent slice thickness and gaps, nonstandardized slice acquisition (not in the subcallosal plane), and incomplete brain coverage, all contribute to scans that are difficult to compare,” he said. Those factors, “allow for assessment of new lesions and lesion activity that are invaluable for diagnosis as well as determining the effectiveness of therapy or the need for initiating/changing therapy.”

Dr. Traboulsee said the lack of adherence to guidelines may simply have to do with a mistaken perception of complexity. “Part of the challenge is MRI centers don’t realize how easy it is to implement these guidelines,” he said in presenting the proposed updates.

Dr. Traboulsee noted that the CMSC has been working with manufacturers to try to incorporate the protocol into the scanners “so that it’s just a button to press” for the MRI. “I think that will get us over a major hurdle of adaptation,” Dr. Traboulsee said. “Most radiologists said once they started using it they were really happy with it. They found they were using it beyond MS for other basic neurologic imaging, so just raising awareness and making things more of a one-step process for individuals to use will be helpful,” he said.
 

Repositioning consistency is key

Among key suggestions that the expert panel proposed for guideline updates include the use of the subcallosal plane for consistent repositioning, which should allow for more accuracy and consistency in the identification of lesions in MS, Dr. Traboulsee said. “A major change reflecting improvements in MRI technology is the ability to acquire high-resolution 3-D images and that’s particularly helpful with fluid attenuation inversion recovery (FLAIR) sequences, which is what we do to identify lesions,” he explained. “The repositioning along the subcallosal line is important because it allows us to easily compare studies over time. It takes very little time but allows us to prepare studies over time much more easily,” he said.

Central vein sign

Another update is the establishment of a new category of optimum plus sequences allowing for the monitoring of brain atrophy and identifying lesions with a central vein sign, which has gained high interest as a marker on 3T MRI of demyelinating plaques in MS. As described in recent research, the central vein sign shows high accuracy in differentiating between MS and non-MS lesions.

“Many people have a few white spots on neuroimaging, but with MRI so much more available around the world, many of them are being misdiagnosed with MS,” Dr. Traboulsee said. “But the central vein sign, using a very simple MRI technique, can identify lesions with a vein in the center that (distinguishes them as) MS lesions.”

Though the process is still several years from routine clinical use, the proposed update would better implement susceptibility weighted imaging, which has traditionally been used for functional MRI.
 

PML Surveillance

The updates also include recommendations to help in the detection of the rare but potentially serious complication of some disease-modifying therapies of progressive multifocal leukoencephalopathy (PML). “We need a very quick and comprehensive way to monitor patients for PML before symptoms develop,” Dr. Traboulsee said. “The sequences we recommended were based on expert opinion of people who have worked quite a bit with PML in MS, and if one wants to survey for PML it’s only about a 10-minute scan.”

International protocol

Corey Ford, MD, a professor of neurology and director of the MS Specialty Clinic at the University of New Mexico Health Sciences Center in Albuquerque, commented that, with imaging playing such an important role in MS, the lack of adherence to the protocol can be a significant hindrance. “MRI is the most important imaging tool we have in the diagnosing and management of MS, but ... it’s quite amazing how different the sequences that are used can be when imaging centers are asked to image someone with a diagnosis of MS, so it’s a problem,” he said.

Dr. Ford speculated that part of the problem is simply inertia at some imaging centers. “Practices will have been programmed into their protocol for a long time, so when a patient comes in for imaging regarding MS, they may [turn to] their typical sequence,” he said. “There is an inertial barrier to upgrading that sequence, which can involve testing it out on the machine, training the techs to do it that way, and interpreting it for the physician clients who requested the imaging.”

In addition, there is a lack of exposure of MS imaging guidelines in the radiology literature, Dr. Ford added. “Maybe it’s a matter of giving more presentations at meetings that include radiologists, or getting the information out through the manufacturers. I think at the end of the day it could be a combination of all of those things,” he said.

However, the CMSC collaboration could make a big difference, Dr. Ford noted. “This is where the international protocol could be important in terms of making all of this happen,” he said. “What we’re seeing is the confluence of representatives of the U.S. and European centers hash out a consensus, and if it’s international, I think that adds a lot of weight to an eventual implementation on a wider basis.”

“I think the group has done a stellar job, and we should not try to be too focused on adding everyone’s little tweak,” he noted. “If we can get a good baseline foundational imaging sequence that can be implemented worldwide, we would be much better off.”

The CMSC updated imaging guidelines are expected to be published in coming months. The most recent previous updates are available online.

Dr. Traboulsee disclosed relationships with Biogen, Chugai, Roche, Sanofi, and Teva. Dr. Ford and Dr. Li have disclosed no relevant financial relationships.

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

Proposed updates to guidelines for magnetic resonance imaging in patients with multiple sclerosis (MS) are in the works to make the Consortium of Multiple Sclerosis Centers protocol and other international guidelines more similar, with the hope that internationally accepted consensus guidelines will improve lagging conformity with the recommendations.

“We’ve always envisioned the guidelines as being international, but now we have harmony with the groups, so this is truly a global protocol,” Anthony Traboulsee, MD, a professor of neurology and director of the MS clinic and neuromyelitis optica clinic at the University of British Columbia in Vancouver, said in presenting the proposed updates during the virtual meeting of the CMSC.

The updates reflect the input of an international expert panel convened by the CMSC in October 2019, made up of neurologists, radiologists, magnetic resonance technologists, and imaging scientists with expertise in MS. Attendees represented groups including the European-based Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, National MS Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis.
 

Standardizing scans

While the mission was to review and update the current guidelines, an important overriding objective was to boost universal acceptance and improve the utilization of the protocol, which research shows is surprisingly low. According to one poster presented at the meeting, a real-world MRI dataset of 1,233 sessions showed only 8% satisfied criteria for the T1 sequence outlined in the 2018 guidelines, and only 7% satisfied criteria for the T2 sequence. “In a real-world MRI dataset of patients with MS, the conformance to the CMSC brain MRI guidelines was extremely low,” concluded the authors, who were with Icometrix, in Chicago and Belgium.

David Li, MD, also of the University of British Columbia and cochair of the MRI guideline committee, said the nonconformity has important implications. “Nonstandardized scans, with inconsistent slice thickness and gaps, nonstandardized slice acquisition (not in the subcallosal plane), and incomplete brain coverage, all contribute to scans that are difficult to compare,” he said. Those factors, “allow for assessment of new lesions and lesion activity that are invaluable for diagnosis as well as determining the effectiveness of therapy or the need for initiating/changing therapy.”

Dr. Traboulsee said the lack of adherence to guidelines may simply have to do with a mistaken perception of complexity. “Part of the challenge is MRI centers don’t realize how easy it is to implement these guidelines,” he said in presenting the proposed updates.

Dr. Traboulsee noted that the CMSC has been working with manufacturers to try to incorporate the protocol into the scanners “so that it’s just a button to press” for the MRI. “I think that will get us over a major hurdle of adaptation,” Dr. Traboulsee said. “Most radiologists said once they started using it they were really happy with it. They found they were using it beyond MS for other basic neurologic imaging, so just raising awareness and making things more of a one-step process for individuals to use will be helpful,” he said.
 

Repositioning consistency is key

Among key suggestions that the expert panel proposed for guideline updates include the use of the subcallosal plane for consistent repositioning, which should allow for more accuracy and consistency in the identification of lesions in MS, Dr. Traboulsee said. “A major change reflecting improvements in MRI technology is the ability to acquire high-resolution 3-D images and that’s particularly helpful with fluid attenuation inversion recovery (FLAIR) sequences, which is what we do to identify lesions,” he explained. “The repositioning along the subcallosal line is important because it allows us to easily compare studies over time. It takes very little time but allows us to prepare studies over time much more easily,” he said.

Central vein sign

Another update is the establishment of a new category of optimum plus sequences allowing for the monitoring of brain atrophy and identifying lesions with a central vein sign, which has gained high interest as a marker on 3T MRI of demyelinating plaques in MS. As described in recent research, the central vein sign shows high accuracy in differentiating between MS and non-MS lesions.

“Many people have a few white spots on neuroimaging, but with MRI so much more available around the world, many of them are being misdiagnosed with MS,” Dr. Traboulsee said. “But the central vein sign, using a very simple MRI technique, can identify lesions with a vein in the center that (distinguishes them as) MS lesions.”

Though the process is still several years from routine clinical use, the proposed update would better implement susceptibility weighted imaging, which has traditionally been used for functional MRI.
 

PML Surveillance

The updates also include recommendations to help in the detection of the rare but potentially serious complication of some disease-modifying therapies of progressive multifocal leukoencephalopathy (PML). “We need a very quick and comprehensive way to monitor patients for PML before symptoms develop,” Dr. Traboulsee said. “The sequences we recommended were based on expert opinion of people who have worked quite a bit with PML in MS, and if one wants to survey for PML it’s only about a 10-minute scan.”

International protocol

Corey Ford, MD, a professor of neurology and director of the MS Specialty Clinic at the University of New Mexico Health Sciences Center in Albuquerque, commented that, with imaging playing such an important role in MS, the lack of adherence to the protocol can be a significant hindrance. “MRI is the most important imaging tool we have in the diagnosing and management of MS, but ... it’s quite amazing how different the sequences that are used can be when imaging centers are asked to image someone with a diagnosis of MS, so it’s a problem,” he said.

Dr. Ford speculated that part of the problem is simply inertia at some imaging centers. “Practices will have been programmed into their protocol for a long time, so when a patient comes in for imaging regarding MS, they may [turn to] their typical sequence,” he said. “There is an inertial barrier to upgrading that sequence, which can involve testing it out on the machine, training the techs to do it that way, and interpreting it for the physician clients who requested the imaging.”

In addition, there is a lack of exposure of MS imaging guidelines in the radiology literature, Dr. Ford added. “Maybe it’s a matter of giving more presentations at meetings that include radiologists, or getting the information out through the manufacturers. I think at the end of the day it could be a combination of all of those things,” he said.

However, the CMSC collaboration could make a big difference, Dr. Ford noted. “This is where the international protocol could be important in terms of making all of this happen,” he said. “What we’re seeing is the confluence of representatives of the U.S. and European centers hash out a consensus, and if it’s international, I think that adds a lot of weight to an eventual implementation on a wider basis.”

“I think the group has done a stellar job, and we should not try to be too focused on adding everyone’s little tweak,” he noted. “If we can get a good baseline foundational imaging sequence that can be implemented worldwide, we would be much better off.”

The CMSC updated imaging guidelines are expected to be published in coming months. The most recent previous updates are available online.

Dr. Traboulsee disclosed relationships with Biogen, Chugai, Roche, Sanofi, and Teva. Dr. Ford and Dr. Li have disclosed no relevant financial relationships.

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

Proposed updates to guidelines for magnetic resonance imaging in patients with multiple sclerosis (MS) are in the works to make the Consortium of Multiple Sclerosis Centers protocol and other international guidelines more similar, with the hope that internationally accepted consensus guidelines will improve lagging conformity with the recommendations.

“We’ve always envisioned the guidelines as being international, but now we have harmony with the groups, so this is truly a global protocol,” Anthony Traboulsee, MD, a professor of neurology and director of the MS clinic and neuromyelitis optica clinic at the University of British Columbia in Vancouver, said in presenting the proposed updates during the virtual meeting of the CMSC.

The updates reflect the input of an international expert panel convened by the CMSC in October 2019, made up of neurologists, radiologists, magnetic resonance technologists, and imaging scientists with expertise in MS. Attendees represented groups including the European-based Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, National MS Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis.
 

Standardizing scans

While the mission was to review and update the current guidelines, an important overriding objective was to boost universal acceptance and improve the utilization of the protocol, which research shows is surprisingly low. According to one poster presented at the meeting, a real-world MRI dataset of 1,233 sessions showed only 8% satisfied criteria for the T1 sequence outlined in the 2018 guidelines, and only 7% satisfied criteria for the T2 sequence. “In a real-world MRI dataset of patients with MS, the conformance to the CMSC brain MRI guidelines was extremely low,” concluded the authors, who were with Icometrix, in Chicago and Belgium.

David Li, MD, also of the University of British Columbia and cochair of the MRI guideline committee, said the nonconformity has important implications. “Nonstandardized scans, with inconsistent slice thickness and gaps, nonstandardized slice acquisition (not in the subcallosal plane), and incomplete brain coverage, all contribute to scans that are difficult to compare,” he said. Those factors, “allow for assessment of new lesions and lesion activity that are invaluable for diagnosis as well as determining the effectiveness of therapy or the need for initiating/changing therapy.”

Dr. Traboulsee said the lack of adherence to guidelines may simply have to do with a mistaken perception of complexity. “Part of the challenge is MRI centers don’t realize how easy it is to implement these guidelines,” he said in presenting the proposed updates.

Dr. Traboulsee noted that the CMSC has been working with manufacturers to try to incorporate the protocol into the scanners “so that it’s just a button to press” for the MRI. “I think that will get us over a major hurdle of adaptation,” Dr. Traboulsee said. “Most radiologists said once they started using it they were really happy with it. They found they were using it beyond MS for other basic neurologic imaging, so just raising awareness and making things more of a one-step process for individuals to use will be helpful,” he said.
 

Repositioning consistency is key

Among key suggestions that the expert panel proposed for guideline updates include the use of the subcallosal plane for consistent repositioning, which should allow for more accuracy and consistency in the identification of lesions in MS, Dr. Traboulsee said. “A major change reflecting improvements in MRI technology is the ability to acquire high-resolution 3-D images and that’s particularly helpful with fluid attenuation inversion recovery (FLAIR) sequences, which is what we do to identify lesions,” he explained. “The repositioning along the subcallosal line is important because it allows us to easily compare studies over time. It takes very little time but allows us to prepare studies over time much more easily,” he said.

Central vein sign

Another update is the establishment of a new category of optimum plus sequences allowing for the monitoring of brain atrophy and identifying lesions with a central vein sign, which has gained high interest as a marker on 3T MRI of demyelinating plaques in MS. As described in recent research, the central vein sign shows high accuracy in differentiating between MS and non-MS lesions.

“Many people have a few white spots on neuroimaging, but with MRI so much more available around the world, many of them are being misdiagnosed with MS,” Dr. Traboulsee said. “But the central vein sign, using a very simple MRI technique, can identify lesions with a vein in the center that (distinguishes them as) MS lesions.”

Though the process is still several years from routine clinical use, the proposed update would better implement susceptibility weighted imaging, which has traditionally been used for functional MRI.
 

PML Surveillance

The updates also include recommendations to help in the detection of the rare but potentially serious complication of some disease-modifying therapies of progressive multifocal leukoencephalopathy (PML). “We need a very quick and comprehensive way to monitor patients for PML before symptoms develop,” Dr. Traboulsee said. “The sequences we recommended were based on expert opinion of people who have worked quite a bit with PML in MS, and if one wants to survey for PML it’s only about a 10-minute scan.”

International protocol

Corey Ford, MD, a professor of neurology and director of the MS Specialty Clinic at the University of New Mexico Health Sciences Center in Albuquerque, commented that, with imaging playing such an important role in MS, the lack of adherence to the protocol can be a significant hindrance. “MRI is the most important imaging tool we have in the diagnosing and management of MS, but ... it’s quite amazing how different the sequences that are used can be when imaging centers are asked to image someone with a diagnosis of MS, so it’s a problem,” he said.

Dr. Ford speculated that part of the problem is simply inertia at some imaging centers. “Practices will have been programmed into their protocol for a long time, so when a patient comes in for imaging regarding MS, they may [turn to] their typical sequence,” he said. “There is an inertial barrier to upgrading that sequence, which can involve testing it out on the machine, training the techs to do it that way, and interpreting it for the physician clients who requested the imaging.”

In addition, there is a lack of exposure of MS imaging guidelines in the radiology literature, Dr. Ford added. “Maybe it’s a matter of giving more presentations at meetings that include radiologists, or getting the information out through the manufacturers. I think at the end of the day it could be a combination of all of those things,” he said.

However, the CMSC collaboration could make a big difference, Dr. Ford noted. “This is where the international protocol could be important in terms of making all of this happen,” he said. “What we’re seeing is the confluence of representatives of the U.S. and European centers hash out a consensus, and if it’s international, I think that adds a lot of weight to an eventual implementation on a wider basis.”

“I think the group has done a stellar job, and we should not try to be too focused on adding everyone’s little tweak,” he noted. “If we can get a good baseline foundational imaging sequence that can be implemented worldwide, we would be much better off.”

The CMSC updated imaging guidelines are expected to be published in coming months. The most recent previous updates are available online.

Dr. Traboulsee disclosed relationships with Biogen, Chugai, Roche, Sanofi, and Teva. Dr. Ford and Dr. Li have disclosed no relevant financial relationships.

A version of this article originally 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.

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.

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.