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Anti-CD20s linked to higher COVID-19 severity in MS
Like other people, a biostatistician told neurologists. With the exception of anti-CD20s, registries also suggest that disease-modifying therapies (DMTs) don’t cause higher degrees of severity.
“It’s good news since it’s important for patients to stay on these treatments,” said Amber Salter, PhD, MPH, an assistant professor at Washington University, St. Louis, in a follow-up interview following her presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Salter reported on the findings of several MS/COVID-19 registries from around the world, including the COViMS Registry, which is supported by the Consortium of MS Centers, the MS Society of Canada, and the National MS Society. It tracks patients who developed COVID-19 while also having MS, neuromyelitis optica, or MOG antibody disease.
The registry began collecting data in April 2020 and is ongoing. As of Jan. 29, 2021, 2,059 patients had been tracked; 85% of cases were confirmed by laboratory tests. Nearly all patients (97%) were from the United States, with about 21% from New York state. Nearly 76% were female, the average age was 48. About 70% were non-Hispanic White, 18% were African American; 83% had relapsing remitting MS, and 17% had progressive MS.
“We found that 11.5% of MS patients were reported being hospitalized, while 4.2% were admitted to the ICU or ventilated and 3% had died,” Dr. Salter said. Not surprisingly, the death rate was highest (21%) in patients aged 75 years or older, compared with 11% of those aged 65-74 years. Those with more severe cases – those who were nonambulatory – had a death rate of 18%, compared with 0.6% of those who were fully ambulatory and 4% of those who walked with assistance.
“A lot of the risks [for COVID-19 severity] we see in the general population are risks in the MS population,” Dr. Salter said.
Dr. Salter also summarized the results of other international registries. After adjustment, a registry in Italy linked the anti-CD20 drugs ocrelizumab or rituximab (odds ratio, 2.37, P = .015) and recent use of methylprednisolone (OR, 5.2; P = .001) to more severe courses of COVID-19, compared with other DMTs. And a global data-sharing project linked anti-CD20s to more severe outcomes, compared with other DMTs (hospitalization, adjusted prevalence ratio, 1.49; ICU admission, aPR, 2.55; and ventilation, aPR, 3.05).
In an interview, neurologist Lauren Gluck, MD, of Albert Einstein College of Medicine and Montefiore Medical Center, both in New York, cautioned that prescribing anti-CD20s now “requires a more complex informed consent process with patients and outlining of risk as well as strategies to minimize contracting the infection.”
Moving forward, she advised colleagues to “keep treating MS with DMTs. Preventing MS attacks will help keep patients out of the hospital and limit need for high-dose steroids.” And she cautioned that “avoiding action due to inaccurate fear of DMTs and COVID-19 may put your patients at unnecessary risk of relapses and accumulated disability. Educate your patients on the reality of the COVID19 pandemic, their personal risk of exposure, and strategies to minimize their risk.”
Fortunately, vaccinations offer protection against COVID-19 in patients with MS, although patients are clearly concerned about potential risks. “A frequent concern is whether the vaccines are safe for MS patients in general and if they could incite MS relapses,” neurologist Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, said in an interview. “The American Academy of Neurology guidelines have not found a connection between vaccination and MS relapses. Having COVID-19 infection can trigger MS relapses, so clearly the benefit from the vaccine outweighs any potential risks. Obviously, it is not advisable to take any vaccine during an active relapse, but vaccines are safe otherwise when given during remission.”
Dr. Salter and Dr. Gluck reported no relevant disclosures. Dr. Abboud reports consulting fees from Biogen, Genentech, Bristol-Myers Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myers Squibb, Genentech, and Sanofi-Genzyme.
Like other people, a biostatistician told neurologists. With the exception of anti-CD20s, registries also suggest that disease-modifying therapies (DMTs) don’t cause higher degrees of severity.
“It’s good news since it’s important for patients to stay on these treatments,” said Amber Salter, PhD, MPH, an assistant professor at Washington University, St. Louis, in a follow-up interview following her presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Salter reported on the findings of several MS/COVID-19 registries from around the world, including the COViMS Registry, which is supported by the Consortium of MS Centers, the MS Society of Canada, and the National MS Society. It tracks patients who developed COVID-19 while also having MS, neuromyelitis optica, or MOG antibody disease.
The registry began collecting data in April 2020 and is ongoing. As of Jan. 29, 2021, 2,059 patients had been tracked; 85% of cases were confirmed by laboratory tests. Nearly all patients (97%) were from the United States, with about 21% from New York state. Nearly 76% were female, the average age was 48. About 70% were non-Hispanic White, 18% were African American; 83% had relapsing remitting MS, and 17% had progressive MS.
“We found that 11.5% of MS patients were reported being hospitalized, while 4.2% were admitted to the ICU or ventilated and 3% had died,” Dr. Salter said. Not surprisingly, the death rate was highest (21%) in patients aged 75 years or older, compared with 11% of those aged 65-74 years. Those with more severe cases – those who were nonambulatory – had a death rate of 18%, compared with 0.6% of those who were fully ambulatory and 4% of those who walked with assistance.
“A lot of the risks [for COVID-19 severity] we see in the general population are risks in the MS population,” Dr. Salter said.
Dr. Salter also summarized the results of other international registries. After adjustment, a registry in Italy linked the anti-CD20 drugs ocrelizumab or rituximab (odds ratio, 2.37, P = .015) and recent use of methylprednisolone (OR, 5.2; P = .001) to more severe courses of COVID-19, compared with other DMTs. And a global data-sharing project linked anti-CD20s to more severe outcomes, compared with other DMTs (hospitalization, adjusted prevalence ratio, 1.49; ICU admission, aPR, 2.55; and ventilation, aPR, 3.05).
In an interview, neurologist Lauren Gluck, MD, of Albert Einstein College of Medicine and Montefiore Medical Center, both in New York, cautioned that prescribing anti-CD20s now “requires a more complex informed consent process with patients and outlining of risk as well as strategies to minimize contracting the infection.”
Moving forward, she advised colleagues to “keep treating MS with DMTs. Preventing MS attacks will help keep patients out of the hospital and limit need for high-dose steroids.” And she cautioned that “avoiding action due to inaccurate fear of DMTs and COVID-19 may put your patients at unnecessary risk of relapses and accumulated disability. Educate your patients on the reality of the COVID19 pandemic, their personal risk of exposure, and strategies to minimize their risk.”
Fortunately, vaccinations offer protection against COVID-19 in patients with MS, although patients are clearly concerned about potential risks. “A frequent concern is whether the vaccines are safe for MS patients in general and if they could incite MS relapses,” neurologist Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, said in an interview. “The American Academy of Neurology guidelines have not found a connection between vaccination and MS relapses. Having COVID-19 infection can trigger MS relapses, so clearly the benefit from the vaccine outweighs any potential risks. Obviously, it is not advisable to take any vaccine during an active relapse, but vaccines are safe otherwise when given during remission.”
Dr. Salter and Dr. Gluck reported no relevant disclosures. Dr. Abboud reports consulting fees from Biogen, Genentech, Bristol-Myers Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myers Squibb, Genentech, and Sanofi-Genzyme.
Like other people, a biostatistician told neurologists. With the exception of anti-CD20s, registries also suggest that disease-modifying therapies (DMTs) don’t cause higher degrees of severity.
“It’s good news since it’s important for patients to stay on these treatments,” said Amber Salter, PhD, MPH, an assistant professor at Washington University, St. Louis, in a follow-up interview following her presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Salter reported on the findings of several MS/COVID-19 registries from around the world, including the COViMS Registry, which is supported by the Consortium of MS Centers, the MS Society of Canada, and the National MS Society. It tracks patients who developed COVID-19 while also having MS, neuromyelitis optica, or MOG antibody disease.
The registry began collecting data in April 2020 and is ongoing. As of Jan. 29, 2021, 2,059 patients had been tracked; 85% of cases were confirmed by laboratory tests. Nearly all patients (97%) were from the United States, with about 21% from New York state. Nearly 76% were female, the average age was 48. About 70% were non-Hispanic White, 18% were African American; 83% had relapsing remitting MS, and 17% had progressive MS.
“We found that 11.5% of MS patients were reported being hospitalized, while 4.2% were admitted to the ICU or ventilated and 3% had died,” Dr. Salter said. Not surprisingly, the death rate was highest (21%) in patients aged 75 years or older, compared with 11% of those aged 65-74 years. Those with more severe cases – those who were nonambulatory – had a death rate of 18%, compared with 0.6% of those who were fully ambulatory and 4% of those who walked with assistance.
“A lot of the risks [for COVID-19 severity] we see in the general population are risks in the MS population,” Dr. Salter said.
Dr. Salter also summarized the results of other international registries. After adjustment, a registry in Italy linked the anti-CD20 drugs ocrelizumab or rituximab (odds ratio, 2.37, P = .015) and recent use of methylprednisolone (OR, 5.2; P = .001) to more severe courses of COVID-19, compared with other DMTs. And a global data-sharing project linked anti-CD20s to more severe outcomes, compared with other DMTs (hospitalization, adjusted prevalence ratio, 1.49; ICU admission, aPR, 2.55; and ventilation, aPR, 3.05).
In an interview, neurologist Lauren Gluck, MD, of Albert Einstein College of Medicine and Montefiore Medical Center, both in New York, cautioned that prescribing anti-CD20s now “requires a more complex informed consent process with patients and outlining of risk as well as strategies to minimize contracting the infection.”
Moving forward, she advised colleagues to “keep treating MS with DMTs. Preventing MS attacks will help keep patients out of the hospital and limit need for high-dose steroids.” And she cautioned that “avoiding action due to inaccurate fear of DMTs and COVID-19 may put your patients at unnecessary risk of relapses and accumulated disability. Educate your patients on the reality of the COVID19 pandemic, their personal risk of exposure, and strategies to minimize their risk.”
Fortunately, vaccinations offer protection against COVID-19 in patients with MS, although patients are clearly concerned about potential risks. “A frequent concern is whether the vaccines are safe for MS patients in general and if they could incite MS relapses,” neurologist Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, said in an interview. “The American Academy of Neurology guidelines have not found a connection between vaccination and MS relapses. Having COVID-19 infection can trigger MS relapses, so clearly the benefit from the vaccine outweighs any potential risks. Obviously, it is not advisable to take any vaccine during an active relapse, but vaccines are safe otherwise when given during remission.”
Dr. Salter and Dr. Gluck reported no relevant disclosures. Dr. Abboud reports consulting fees from Biogen, Genentech, Bristol-Myers Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myers Squibb, Genentech, and Sanofi-Genzyme.
FROM ACTRIMS FORUM 2021
Certain DMTs in MS may attenuate COVID-19 vaccines
“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.
“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”
Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”
In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”
Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”
Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.
Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).
Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.
He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”
Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”
Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.
“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”
Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”
In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”
Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”
Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.
Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).
Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.
He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”
Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”
Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.
“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”
Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”
In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”
Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”
Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.
Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).
Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.
He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”
Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”
Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
FROM ACTRIMS FORUM 2021
Natalizumab postinfusion reactions rare; is monitoring necessary?
new studies show.
Collectively, the results suggest the need to rethink the drug’s mandatory 1-hour postinfusion observation period – particularly when unnecessarily spending time in medical settings is discouraged because of concerns regarding COVID-19, the researchers concluded.
Their findings “highlight a potential opportunity to improve and streamline the infusion and postinfusion monitoring process,” reported the authors of one of the studies. The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Infusion reactions were rare
“In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions,” they said.
The 1-hour postinfusion observation period for natalizumab, approved for the treatment of relapsing remitting MS (RRMS), is mandated by the Food and Drug Administration, as well as the European Medicines Agency, and applies to each dose, regardless of treatment duration, owing to concerns of infusion reactions. However, previous evidence has indicated that reactions are rare and are usually mild.
In addition to adding burden to the treatment regimen for patients and providers alike, any extended time in an environment where there is concern of heightened risk for SARS-CoV-2 exposure is a concern.
To evaluate the frequency, severity, and timing of infusion reactions, Yujie Wang, MD, of the department of neurology at the University of Washington, Seattle, and colleagues reviewed medical records of all patients who received natalizumab at the University of Washington MS Center’s infusion suite between July 2012 and September 2020.
Among 333 patients with RRMS, 9,682 infusions of natalizumab were provided over the study period, with a mean of 27 infusions per patient (range, 1-174). The mean age of the patients was 41 years, and 87 (26%) were male.
Overall, 33 infusion-related adverse events were reported in 26 patients, representing 0.34% of total infusions and 7.8% of patients.
In 77% of cases, the adverse event occurred during the infusion. In 92% of cases, the adverse event occurred within the first 6 months of treatment.
All of the events were described as mild. The most common were itching, gastrointestinal problems, headache, and flushing.
None of the reactions required emergency care or hospitalization. Symptoms were either self-managed or were managed easily with standard care. The treatment was continued in all cases.
“For physicians and providers who care for patients with MS and are comfortable with infusible therapies, it is no surprise that rates of clinically significant infusion reactions were low,” Dr. Wang said. “It is indeed consistent with prior studies that reactions generally occur during rather than post infusion.”
The authors underscored the array of potential benefits in making changes to the requirement. “Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients’ treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.”
Additional studies show consistent findings
Several other recent studies have shown similar results. In a study published in Multiple Sclerosis in October 2020, researchers with the Amsterdam University Medical Center found that, among 14,174 natalizumab infusions provided to 225 patients with RRMS between 2006 and 2018, 276 infusion-related adverse events occurred (1.95%) among 60 patients.
There were 11 severe infusion-related adverse events in nine patients (4.0%). All documented severe reactions occurred during the infusion. Among 19 moderate adverse events, 17 occurred during the infusion.
The researchers noted that the majority of patients who experienced severe infusion reactions had detectable antibodies against natalizumab. Such antibodies are associated with a higher risk for infusion-related adverse events.
Patients who did not have any symptoms of a reaction during the infusion had no clinically relevant moderate or severe reactions.
“Thus, the need for postinfusion observation will depend on the patients’ clinical status during the infusion,” they wrote. “Consequently, our data suggest that patients who do not have an infusion-related adverse event while receiving natalizumab treatment do not need to stay in the hospital for an additional observation hour.”
Rapid infusion protocol
In another recent study published in Multiple Sclerosis and Related Disorders in January 2021, researchers in Australia reported on the use of a rapid infusion protocol of natalizumab and ocrelizumab. The protocol was implemented to reduce the amount of time patients are required to spend in clinical settings during the COVID-19 pandemic.
In their analysis of 269 rapid infusions of natalizumab and 100 rapid infusions of ocrelizumab, there were two infusion-related reactions in the natalizumab group and eight in the ocrelizumab group.
All the reactions were mild to moderate, and no discontinuations were required. None of the reactions occurred during the postinfusion observation period.
“In the setting of COVID-19 pandemic, rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis,” the authors wrote.
Under the rapid infusion protocol, patients receive three standard doses for 1 hour followed by 30 minutes of observation. In addition, infusions are reduced to 30 minutes, explained lead author Louise Rath, of clinical neurosciences, Alfred Health, in Melbourne.
“For our cohort of patients, the side effects were minimal,” she said.
“Rapid infusions allowed patients to have option of hospital in-home or office, ensuring work was not at risk by infusion,” she added. “Our governance has been very supportive, and we will be keeping rapid infusion post COVID.”
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new studies show.
Collectively, the results suggest the need to rethink the drug’s mandatory 1-hour postinfusion observation period – particularly when unnecessarily spending time in medical settings is discouraged because of concerns regarding COVID-19, the researchers concluded.
Their findings “highlight a potential opportunity to improve and streamline the infusion and postinfusion monitoring process,” reported the authors of one of the studies. The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Infusion reactions were rare
“In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions,” they said.
The 1-hour postinfusion observation period for natalizumab, approved for the treatment of relapsing remitting MS (RRMS), is mandated by the Food and Drug Administration, as well as the European Medicines Agency, and applies to each dose, regardless of treatment duration, owing to concerns of infusion reactions. However, previous evidence has indicated that reactions are rare and are usually mild.
In addition to adding burden to the treatment regimen for patients and providers alike, any extended time in an environment where there is concern of heightened risk for SARS-CoV-2 exposure is a concern.
To evaluate the frequency, severity, and timing of infusion reactions, Yujie Wang, MD, of the department of neurology at the University of Washington, Seattle, and colleagues reviewed medical records of all patients who received natalizumab at the University of Washington MS Center’s infusion suite between July 2012 and September 2020.
Among 333 patients with RRMS, 9,682 infusions of natalizumab were provided over the study period, with a mean of 27 infusions per patient (range, 1-174). The mean age of the patients was 41 years, and 87 (26%) were male.
Overall, 33 infusion-related adverse events were reported in 26 patients, representing 0.34% of total infusions and 7.8% of patients.
In 77% of cases, the adverse event occurred during the infusion. In 92% of cases, the adverse event occurred within the first 6 months of treatment.
All of the events were described as mild. The most common were itching, gastrointestinal problems, headache, and flushing.
None of the reactions required emergency care or hospitalization. Symptoms were either self-managed or were managed easily with standard care. The treatment was continued in all cases.
“For physicians and providers who care for patients with MS and are comfortable with infusible therapies, it is no surprise that rates of clinically significant infusion reactions were low,” Dr. Wang said. “It is indeed consistent with prior studies that reactions generally occur during rather than post infusion.”
The authors underscored the array of potential benefits in making changes to the requirement. “Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients’ treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.”
Additional studies show consistent findings
Several other recent studies have shown similar results. In a study published in Multiple Sclerosis in October 2020, researchers with the Amsterdam University Medical Center found that, among 14,174 natalizumab infusions provided to 225 patients with RRMS between 2006 and 2018, 276 infusion-related adverse events occurred (1.95%) among 60 patients.
There were 11 severe infusion-related adverse events in nine patients (4.0%). All documented severe reactions occurred during the infusion. Among 19 moderate adverse events, 17 occurred during the infusion.
The researchers noted that the majority of patients who experienced severe infusion reactions had detectable antibodies against natalizumab. Such antibodies are associated with a higher risk for infusion-related adverse events.
Patients who did not have any symptoms of a reaction during the infusion had no clinically relevant moderate or severe reactions.
“Thus, the need for postinfusion observation will depend on the patients’ clinical status during the infusion,” they wrote. “Consequently, our data suggest that patients who do not have an infusion-related adverse event while receiving natalizumab treatment do not need to stay in the hospital for an additional observation hour.”
Rapid infusion protocol
In another recent study published in Multiple Sclerosis and Related Disorders in January 2021, researchers in Australia reported on the use of a rapid infusion protocol of natalizumab and ocrelizumab. The protocol was implemented to reduce the amount of time patients are required to spend in clinical settings during the COVID-19 pandemic.
In their analysis of 269 rapid infusions of natalizumab and 100 rapid infusions of ocrelizumab, there were two infusion-related reactions in the natalizumab group and eight in the ocrelizumab group.
All the reactions were mild to moderate, and no discontinuations were required. None of the reactions occurred during the postinfusion observation period.
“In the setting of COVID-19 pandemic, rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis,” the authors wrote.
Under the rapid infusion protocol, patients receive three standard doses for 1 hour followed by 30 minutes of observation. In addition, infusions are reduced to 30 minutes, explained lead author Louise Rath, of clinical neurosciences, Alfred Health, in Melbourne.
“For our cohort of patients, the side effects were minimal,” she said.
“Rapid infusions allowed patients to have option of hospital in-home or office, ensuring work was not at risk by infusion,” she added. “Our governance has been very supportive, and we will be keeping rapid infusion post COVID.”
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new studies show.
Collectively, the results suggest the need to rethink the drug’s mandatory 1-hour postinfusion observation period – particularly when unnecessarily spending time in medical settings is discouraged because of concerns regarding COVID-19, the researchers concluded.
Their findings “highlight a potential opportunity to improve and streamline the infusion and postinfusion monitoring process,” reported the authors of one of the studies. The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Infusion reactions were rare
“In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions,” they said.
The 1-hour postinfusion observation period for natalizumab, approved for the treatment of relapsing remitting MS (RRMS), is mandated by the Food and Drug Administration, as well as the European Medicines Agency, and applies to each dose, regardless of treatment duration, owing to concerns of infusion reactions. However, previous evidence has indicated that reactions are rare and are usually mild.
In addition to adding burden to the treatment regimen for patients and providers alike, any extended time in an environment where there is concern of heightened risk for SARS-CoV-2 exposure is a concern.
To evaluate the frequency, severity, and timing of infusion reactions, Yujie Wang, MD, of the department of neurology at the University of Washington, Seattle, and colleagues reviewed medical records of all patients who received natalizumab at the University of Washington MS Center’s infusion suite between July 2012 and September 2020.
Among 333 patients with RRMS, 9,682 infusions of natalizumab were provided over the study period, with a mean of 27 infusions per patient (range, 1-174). The mean age of the patients was 41 years, and 87 (26%) were male.
Overall, 33 infusion-related adverse events were reported in 26 patients, representing 0.34% of total infusions and 7.8% of patients.
In 77% of cases, the adverse event occurred during the infusion. In 92% of cases, the adverse event occurred within the first 6 months of treatment.
All of the events were described as mild. The most common were itching, gastrointestinal problems, headache, and flushing.
None of the reactions required emergency care or hospitalization. Symptoms were either self-managed or were managed easily with standard care. The treatment was continued in all cases.
“For physicians and providers who care for patients with MS and are comfortable with infusible therapies, it is no surprise that rates of clinically significant infusion reactions were low,” Dr. Wang said. “It is indeed consistent with prior studies that reactions generally occur during rather than post infusion.”
The authors underscored the array of potential benefits in making changes to the requirement. “Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients’ treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.”
Additional studies show consistent findings
Several other recent studies have shown similar results. In a study published in Multiple Sclerosis in October 2020, researchers with the Amsterdam University Medical Center found that, among 14,174 natalizumab infusions provided to 225 patients with RRMS between 2006 and 2018, 276 infusion-related adverse events occurred (1.95%) among 60 patients.
There were 11 severe infusion-related adverse events in nine patients (4.0%). All documented severe reactions occurred during the infusion. Among 19 moderate adverse events, 17 occurred during the infusion.
The researchers noted that the majority of patients who experienced severe infusion reactions had detectable antibodies against natalizumab. Such antibodies are associated with a higher risk for infusion-related adverse events.
Patients who did not have any symptoms of a reaction during the infusion had no clinically relevant moderate or severe reactions.
“Thus, the need for postinfusion observation will depend on the patients’ clinical status during the infusion,” they wrote. “Consequently, our data suggest that patients who do not have an infusion-related adverse event while receiving natalizumab treatment do not need to stay in the hospital for an additional observation hour.”
Rapid infusion protocol
In another recent study published in Multiple Sclerosis and Related Disorders in January 2021, researchers in Australia reported on the use of a rapid infusion protocol of natalizumab and ocrelizumab. The protocol was implemented to reduce the amount of time patients are required to spend in clinical settings during the COVID-19 pandemic.
In their analysis of 269 rapid infusions of natalizumab and 100 rapid infusions of ocrelizumab, there were two infusion-related reactions in the natalizumab group and eight in the ocrelizumab group.
All the reactions were mild to moderate, and no discontinuations were required. None of the reactions occurred during the postinfusion observation period.
“In the setting of COVID-19 pandemic, rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis,” the authors wrote.
Under the rapid infusion protocol, patients receive three standard doses for 1 hour followed by 30 minutes of observation. In addition, infusions are reduced to 30 minutes, explained lead author Louise Rath, of clinical neurosciences, Alfred Health, in Melbourne.
“For our cohort of patients, the side effects were minimal,” she said.
“Rapid infusions allowed patients to have option of hospital in-home or office, ensuring work was not at risk by infusion,” she added. “Our governance has been very supportive, and we will be keeping rapid infusion post COVID.”
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACTRIMS 2021
NfL levels linked to worse disability in real-world MS
according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.
“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”
The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Scrutinizing serum neurofilament light chain levels in a real-world cohort
Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.
To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.
Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).
Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.
A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).
Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.
Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m2 increase in BMI).
Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).
Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”
The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.
The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”
Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.
“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
Applying the findings to individual patients
Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.
“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.
“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.
Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.
“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added.
Future research
In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.
The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.
“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”
The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.
“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”
The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Scrutinizing serum neurofilament light chain levels in a real-world cohort
Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.
To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.
Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).
Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.
A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).
Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.
Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m2 increase in BMI).
Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).
Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”
The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.
The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”
Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.
“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
Applying the findings to individual patients
Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.
“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.
“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.
Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.
“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added.
Future research
In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.
The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.
“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”
The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.
“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”
The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Scrutinizing serum neurofilament light chain levels in a real-world cohort
Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.
To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.
Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).
Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.
A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).
Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.
Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m2 increase in BMI).
Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).
Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”
The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.
The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”
Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.
“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
Applying the findings to individual patients
Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.
“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.
“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.
Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.
“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added.
Future research
In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.
The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.
“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”
The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACTRIMS 2021
Vitamin D deficiency linked to early cognitive impairment in MS
according to new research that adds to the known adverse relationship between low vitamin D and MS.
“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.
“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.
The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Low vitamin D and MS
Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.
“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”
To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.
Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.
At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.
The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).
Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).
Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).
Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).
Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.
Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”
The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.
“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.
“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
Vitamin D also linked to long-term cognitive function
The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.
That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.
“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new research that adds to the known adverse relationship between low vitamin D and MS.
“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.
“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.
The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Low vitamin D and MS
Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.
“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”
To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.
Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.
At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.
The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).
Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).
Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).
Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).
Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.
Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”
The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.
“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.
“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
Vitamin D also linked to long-term cognitive function
The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.
That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.
“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new research that adds to the known adverse relationship between low vitamin D and MS.
“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.
“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.
The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Low vitamin D and MS
Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.
“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”
To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.
Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.
At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.
The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).
Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).
Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).
Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).
Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.
Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”
The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.
“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.
“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
Vitamin D also linked to long-term cognitive function
The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.
That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.
“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACTRIMS FORUM 2021
Opioid use common for pain in multiple sclerosis
, new research shows.
“This high level of opioid use supports that better pain management treatment options, including nonpharmacological options, are needed for people with MS and pain,” wrote the authors of the study, which was presented at ACTRIMS Forum 2021, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Previous research has shown that more than 50% of people with MS report chronic pain that is serious enough to interfere with daily activities, employment, and quality of life. Many with MS report that pain is one of their worst symptoms, the authors noted.
With surprisingly few studies evaluating opioid use in the MS population, Cinda L. Hugos, PT, associate professor of neurology with the VA Portland Health Care System and the department of neurology, Oregon Health and Science University, Portland, and colleagues investigated the issue in a sample of patients participating in a U.S. multisite MS fatigue management trial conducted between 2013 and 2014.
Of the 281 participants with MS in the study, 58 patients (20.6%) reported using prescription opioids. Among them, most – 44 (76%) – reported regular daily use, 10 (17%) reported using the drugs only as needed, 3 (5%) reported only short-term use, including after recent injury or dental surgery, and 1 provided incomplete information.
Those who reported opioid use had significantly worse fatigue scores on the Modified Fatigue Impact Scale (P = .015) and worse pain scores (P < .0001).
There were no significant differences in terms of age (mean age, 53 years), gender (69% were female), or race (in both groups, about 76% were White). No significant differences were seen in disability or depression scores in the opioid users versus nonusers.
“In this sample of people with multiple sclerosis who self-reported fatigue and volunteered to join an MS fatigue management research study, more than one in five reported using prescription opioids and nearly one in six used opioids daily,” the authors wrote. “Opioid users had more pain and fatigue than nonusers.”
Commenting on the study, Jeffrey Cohen, MD, president of ACTRIMS, said that the findings are consistent with his observations that “in the general population, opioids often are used to treat chronic pain in people with MS.”
But they’re not getting the drugs from his clinic. “We do not prescribe opioids in our clinic, referring such patients to a chronic pain program,” Dr. Cohen said. “However, there clearly is need for better treatment options.”
A previous study on opioid use by people with MS, published in 2015, found even higher rates – 42% reported having ever used opioids, and 38% reported currently using opioids.
Although reports of opioid use by patients with MS have been lacking, more has been published on the emerging use of cannabis-related products. One recent study showed that nearly half of people with MS reported using a cannabis-based therapy for nerve-based pain and sleep disturbances.
Although cannabis is considered safer than opioids, the authors noted that it has its own significant drawback – a “paucity of provider guidance.”
“The range of perceived benefits and potential differential effects of THC and cannabinoid highlight the need for personalized, evidence-based guidelines regarding cannabinoid use,” they wrote.
Stretching program for spasticity shows benefits
With spasticity representing a key contributor to MS pain and affecting more than 80% of people with MS, Ms. Hugos and colleagues are developing an alternative to medication – a nonpharmacologic stretching regimen called Spasticity: Take Control” (STC).
Based on evidence-based strategies for the treatment of spasticity in MS, the program involves exercises with daily routines of 15-20 minutes over 6 months.
In a pilot study of 66 patients, also presented at the ACTRIMS meeting, the investigators reported that the program showed significant reductions in pain severity and interference, measured with the Brief Pain Inventory–Short Form, compared with a control consisting of range of motion instruction over 6 months.
The study also offered insights on the specific areas of pain. Among those who reported chronic pain (42% in the STC group and 63.3% in the range-of-motion group), the pain was most frequently reported in the lower back (74.3%), legs (68.6%), or lower back and legs (88.6%).
Ms. Hugos noted that the findings suggest a potentially important nonpharmacologic alternative to spasticity-related pain in MS.
“Stretching is the cornerstone treatment for spasticity from all causes, but there is very little information on stretching exercises in MS or any other conditions,” Ms. Hugos said. “[Our] pilot study is the first and only study using a standardized, daily stretching exercise program to treat MS spasticity,” she said.
“A fully powered study is needed to better understand the impact of different types of exercise on pain severity and interference in multiple sclerosis,” she noted.
Ms. Hugos has received consulting fees from Greenwich Biosciences, Evidera, and Techspert.io. Dr. Cohen has received personal compensation for consulting for Adamas, Atara, Bristol-Myers Squibb, Convelo, MedDay, and Mylan.
A version of this article first appeared on Medscape.com.
, new research shows.
“This high level of opioid use supports that better pain management treatment options, including nonpharmacological options, are needed for people with MS and pain,” wrote the authors of the study, which was presented at ACTRIMS Forum 2021, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Previous research has shown that more than 50% of people with MS report chronic pain that is serious enough to interfere with daily activities, employment, and quality of life. Many with MS report that pain is one of their worst symptoms, the authors noted.
With surprisingly few studies evaluating opioid use in the MS population, Cinda L. Hugos, PT, associate professor of neurology with the VA Portland Health Care System and the department of neurology, Oregon Health and Science University, Portland, and colleagues investigated the issue in a sample of patients participating in a U.S. multisite MS fatigue management trial conducted between 2013 and 2014.
Of the 281 participants with MS in the study, 58 patients (20.6%) reported using prescription opioids. Among them, most – 44 (76%) – reported regular daily use, 10 (17%) reported using the drugs only as needed, 3 (5%) reported only short-term use, including after recent injury or dental surgery, and 1 provided incomplete information.
Those who reported opioid use had significantly worse fatigue scores on the Modified Fatigue Impact Scale (P = .015) and worse pain scores (P < .0001).
There were no significant differences in terms of age (mean age, 53 years), gender (69% were female), or race (in both groups, about 76% were White). No significant differences were seen in disability or depression scores in the opioid users versus nonusers.
“In this sample of people with multiple sclerosis who self-reported fatigue and volunteered to join an MS fatigue management research study, more than one in five reported using prescription opioids and nearly one in six used opioids daily,” the authors wrote. “Opioid users had more pain and fatigue than nonusers.”
Commenting on the study, Jeffrey Cohen, MD, president of ACTRIMS, said that the findings are consistent with his observations that “in the general population, opioids often are used to treat chronic pain in people with MS.”
But they’re not getting the drugs from his clinic. “We do not prescribe opioids in our clinic, referring such patients to a chronic pain program,” Dr. Cohen said. “However, there clearly is need for better treatment options.”
A previous study on opioid use by people with MS, published in 2015, found even higher rates – 42% reported having ever used opioids, and 38% reported currently using opioids.
Although reports of opioid use by patients with MS have been lacking, more has been published on the emerging use of cannabis-related products. One recent study showed that nearly half of people with MS reported using a cannabis-based therapy for nerve-based pain and sleep disturbances.
Although cannabis is considered safer than opioids, the authors noted that it has its own significant drawback – a “paucity of provider guidance.”
“The range of perceived benefits and potential differential effects of THC and cannabinoid highlight the need for personalized, evidence-based guidelines regarding cannabinoid use,” they wrote.
Stretching program for spasticity shows benefits
With spasticity representing a key contributor to MS pain and affecting more than 80% of people with MS, Ms. Hugos and colleagues are developing an alternative to medication – a nonpharmacologic stretching regimen called Spasticity: Take Control” (STC).
Based on evidence-based strategies for the treatment of spasticity in MS, the program involves exercises with daily routines of 15-20 minutes over 6 months.
In a pilot study of 66 patients, also presented at the ACTRIMS meeting, the investigators reported that the program showed significant reductions in pain severity and interference, measured with the Brief Pain Inventory–Short Form, compared with a control consisting of range of motion instruction over 6 months.
The study also offered insights on the specific areas of pain. Among those who reported chronic pain (42% in the STC group and 63.3% in the range-of-motion group), the pain was most frequently reported in the lower back (74.3%), legs (68.6%), or lower back and legs (88.6%).
Ms. Hugos noted that the findings suggest a potentially important nonpharmacologic alternative to spasticity-related pain in MS.
“Stretching is the cornerstone treatment for spasticity from all causes, but there is very little information on stretching exercises in MS or any other conditions,” Ms. Hugos said. “[Our] pilot study is the first and only study using a standardized, daily stretching exercise program to treat MS spasticity,” she said.
“A fully powered study is needed to better understand the impact of different types of exercise on pain severity and interference in multiple sclerosis,” she noted.
Ms. Hugos has received consulting fees from Greenwich Biosciences, Evidera, and Techspert.io. Dr. Cohen has received personal compensation for consulting for Adamas, Atara, Bristol-Myers Squibb, Convelo, MedDay, and Mylan.
A version of this article first appeared on Medscape.com.
, new research shows.
“This high level of opioid use supports that better pain management treatment options, including nonpharmacological options, are needed for people with MS and pain,” wrote the authors of the study, which was presented at ACTRIMS Forum 2021, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Previous research has shown that more than 50% of people with MS report chronic pain that is serious enough to interfere with daily activities, employment, and quality of life. Many with MS report that pain is one of their worst symptoms, the authors noted.
With surprisingly few studies evaluating opioid use in the MS population, Cinda L. Hugos, PT, associate professor of neurology with the VA Portland Health Care System and the department of neurology, Oregon Health and Science University, Portland, and colleagues investigated the issue in a sample of patients participating in a U.S. multisite MS fatigue management trial conducted between 2013 and 2014.
Of the 281 participants with MS in the study, 58 patients (20.6%) reported using prescription opioids. Among them, most – 44 (76%) – reported regular daily use, 10 (17%) reported using the drugs only as needed, 3 (5%) reported only short-term use, including after recent injury or dental surgery, and 1 provided incomplete information.
Those who reported opioid use had significantly worse fatigue scores on the Modified Fatigue Impact Scale (P = .015) and worse pain scores (P < .0001).
There were no significant differences in terms of age (mean age, 53 years), gender (69% were female), or race (in both groups, about 76% were White). No significant differences were seen in disability or depression scores in the opioid users versus nonusers.
“In this sample of people with multiple sclerosis who self-reported fatigue and volunteered to join an MS fatigue management research study, more than one in five reported using prescription opioids and nearly one in six used opioids daily,” the authors wrote. “Opioid users had more pain and fatigue than nonusers.”
Commenting on the study, Jeffrey Cohen, MD, president of ACTRIMS, said that the findings are consistent with his observations that “in the general population, opioids often are used to treat chronic pain in people with MS.”
But they’re not getting the drugs from his clinic. “We do not prescribe opioids in our clinic, referring such patients to a chronic pain program,” Dr. Cohen said. “However, there clearly is need for better treatment options.”
A previous study on opioid use by people with MS, published in 2015, found even higher rates – 42% reported having ever used opioids, and 38% reported currently using opioids.
Although reports of opioid use by patients with MS have been lacking, more has been published on the emerging use of cannabis-related products. One recent study showed that nearly half of people with MS reported using a cannabis-based therapy for nerve-based pain and sleep disturbances.
Although cannabis is considered safer than opioids, the authors noted that it has its own significant drawback – a “paucity of provider guidance.”
“The range of perceived benefits and potential differential effects of THC and cannabinoid highlight the need for personalized, evidence-based guidelines regarding cannabinoid use,” they wrote.
Stretching program for spasticity shows benefits
With spasticity representing a key contributor to MS pain and affecting more than 80% of people with MS, Ms. Hugos and colleagues are developing an alternative to medication – a nonpharmacologic stretching regimen called Spasticity: Take Control” (STC).
Based on evidence-based strategies for the treatment of spasticity in MS, the program involves exercises with daily routines of 15-20 minutes over 6 months.
In a pilot study of 66 patients, also presented at the ACTRIMS meeting, the investigators reported that the program showed significant reductions in pain severity and interference, measured with the Brief Pain Inventory–Short Form, compared with a control consisting of range of motion instruction over 6 months.
The study also offered insights on the specific areas of pain. Among those who reported chronic pain (42% in the STC group and 63.3% in the range-of-motion group), the pain was most frequently reported in the lower back (74.3%), legs (68.6%), or lower back and legs (88.6%).
Ms. Hugos noted that the findings suggest a potentially important nonpharmacologic alternative to spasticity-related pain in MS.
“Stretching is the cornerstone treatment for spasticity from all causes, but there is very little information on stretching exercises in MS or any other conditions,” Ms. Hugos said. “[Our] pilot study is the first and only study using a standardized, daily stretching exercise program to treat MS spasticity,” she said.
“A fully powered study is needed to better understand the impact of different types of exercise on pain severity and interference in multiple sclerosis,” she noted.
Ms. Hugos has received consulting fees from Greenwich Biosciences, Evidera, and Techspert.io. Dr. Cohen has received personal compensation for consulting for Adamas, Atara, Bristol-Myers Squibb, Convelo, MedDay, and Mylan.
A version of this article first appeared on Medscape.com.
FROM ACTRIMS FORUM 2021
MS bears no effect on certain pregnancy complications, stillbirth, or congenital deformation
, according to a new study published online Feb. 3 in Neurology Clinical Practice. While pregnancy and childbirth are not regarded as conditions that engender high-risk pregnancy in the MS population, previous studies evaluating the effects of MS on pregnancy and parturition have yet to fully elucidate some outcomes for pregnant women and their babies in multiple sclerosis.
“Women with multiple sclerosis may be understandably concerned about the risk of pregnancy,” said Melinda Magyari, MD, PhD, a consultant at the University of Copenhagen. “While previous research has shown there is no higher risk of birth defect for babies born to women with MS, we wanted to find out if women with MS are at risk for a variety of pregnancy complications.”
MS is regarded as a progressive, neurological disease mediated by the immune system that demands careful consideration of numerous situations and life changes including family planning. The MS population is overwhelmingly female, as women account for three out of every four cases of MS. The majority of these women range from 20 to 40 years of age at the time of being diagnosed with MS. Despite the unknown risks of pregnancy-related complications and various perinatal complications in this patient population, women who have MS are not discouraged from conceiving.
Assessing pregnancy outcomes
This nationwide, population-based, cross-sectional study evaluated the pregnancies of 2,930 women with MS between Jan. 1, 1997, and Dec. 31, 2016, registered in the Danish Multiple Sclerosis Registry. The researchers compared pregnancy-related and prenatal outcomes to a 5% random sample of 56,958 randomly-selected pregnant women from Denmark’s general population who did not have MS. They found no differences in the risks associated with several pregnancy-related complications (e.g., preeclampsia, gestational diabetes, or placental complications), emergency Cesarean section (C-section), instrumental delivery, stillbirth, preterm birth, or congenital malformation. Apgar scores were low in both groups. A composite of various biometrics in newborns such as reflexes, muscle tone, and heart rate immediately following birth, the Apgar score is used to help assess the neonatal health, with a value of less than 7 considered low. Here, preterm birth is defined as delivery occurring before 37 weeks of gestation, and stillbirth describes a fetus born dead after 22 weeks of gestation.
Women in the MS cohort were more likely to have elective C-sections (odds ratio, 2.89 [95% confidence interval, 1.65-2.16]), induced labor (OR, 1.15 [95%CI, 1.01-1.31]) and have babies with low birth weight based on their gestational age (OR, 1.29 [95% CI, 1.04-1.60]). Nearly 30% of babies born in the cohort (n = 851) were born to mothers who had received disease-modifying therapy (DMT). Neonates exposed to DMT weighed an average of 116 g less than babies born to mothers who had not received DMT (3,378 g vs. 3,494 g) with a slightly lower gestational age (39 weeks as opposed to 40 weeks). However, babies born to mothers with MS were less likely to show signs of asphyxia (OR, 0.87 [95% CI, 0.78-0.97]) than the comparison cohort.
“We found overall, their pregnancies were just as healthy as those of the moms without MS,” Dr. Magyari said.
Comprehensive data
Denmark’s health care system has two key features that make it an attractive setting in which to conduct such a study – the first being its universal health care. The second advantage is that the country enacted several health registries in the 1970s and 1980s that enable the collection of more comprehensive data. For example, the Danish National Patient Register is a population-based registry that spans the entire nation, facilitating epidemiological research with what the study’s authors describe as “high generalizability.” Providing additional insights regarding the patient story helps add context to pregnancy and outcomes. Among the data collected on the women studied were demographics, contact information, and abortions, both spontaneous and medically induced. The country uses other databases and registries to capture additional data. For example, the Register of Legally Induced Abortions provides data regarding the context of medically induced abortions. In contrast, the Danish Medical Birth Registry provides context regarding specified variables regarding women’s pregnancies, delivery, and perinatal outcomes. Finally, the population’s education register offers information regarding patients’ educational history.
A key strength of this study is that the long duration of follow-up data from the Danish Medical Birth Registry, along with its comprehensive data collection, eliminates recall bias. Universal access to health care also improves the generalizability of data. A limitation of the study is its lack of data on maternal smoking and its effects on low gestational weights. The study also has some data gaps, including body mass index information missing from a large portion of the cohort. Finally, the sample size of newborns born to mothers who had received DMT therapy within the last 6 months of gestation was too underpowered to stratify based on first on first-line or second-line treatment.
Dr. Magyari served on scientific advisory boards for Biogen, Sanofi, Teva, Roche, Novartis, and Merck. She has also received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Teva, Roche, Merck, and Novartis. Coauthors disclosed various fees received from Merck, Novartis, Biogen, Roche, Sanofi Genzyme, and Teva.
, according to a new study published online Feb. 3 in Neurology Clinical Practice. While pregnancy and childbirth are not regarded as conditions that engender high-risk pregnancy in the MS population, previous studies evaluating the effects of MS on pregnancy and parturition have yet to fully elucidate some outcomes for pregnant women and their babies in multiple sclerosis.
“Women with multiple sclerosis may be understandably concerned about the risk of pregnancy,” said Melinda Magyari, MD, PhD, a consultant at the University of Copenhagen. “While previous research has shown there is no higher risk of birth defect for babies born to women with MS, we wanted to find out if women with MS are at risk for a variety of pregnancy complications.”
MS is regarded as a progressive, neurological disease mediated by the immune system that demands careful consideration of numerous situations and life changes including family planning. The MS population is overwhelmingly female, as women account for three out of every four cases of MS. The majority of these women range from 20 to 40 years of age at the time of being diagnosed with MS. Despite the unknown risks of pregnancy-related complications and various perinatal complications in this patient population, women who have MS are not discouraged from conceiving.
Assessing pregnancy outcomes
This nationwide, population-based, cross-sectional study evaluated the pregnancies of 2,930 women with MS between Jan. 1, 1997, and Dec. 31, 2016, registered in the Danish Multiple Sclerosis Registry. The researchers compared pregnancy-related and prenatal outcomes to a 5% random sample of 56,958 randomly-selected pregnant women from Denmark’s general population who did not have MS. They found no differences in the risks associated with several pregnancy-related complications (e.g., preeclampsia, gestational diabetes, or placental complications), emergency Cesarean section (C-section), instrumental delivery, stillbirth, preterm birth, or congenital malformation. Apgar scores were low in both groups. A composite of various biometrics in newborns such as reflexes, muscle tone, and heart rate immediately following birth, the Apgar score is used to help assess the neonatal health, with a value of less than 7 considered low. Here, preterm birth is defined as delivery occurring before 37 weeks of gestation, and stillbirth describes a fetus born dead after 22 weeks of gestation.
Women in the MS cohort were more likely to have elective C-sections (odds ratio, 2.89 [95% confidence interval, 1.65-2.16]), induced labor (OR, 1.15 [95%CI, 1.01-1.31]) and have babies with low birth weight based on their gestational age (OR, 1.29 [95% CI, 1.04-1.60]). Nearly 30% of babies born in the cohort (n = 851) were born to mothers who had received disease-modifying therapy (DMT). Neonates exposed to DMT weighed an average of 116 g less than babies born to mothers who had not received DMT (3,378 g vs. 3,494 g) with a slightly lower gestational age (39 weeks as opposed to 40 weeks). However, babies born to mothers with MS were less likely to show signs of asphyxia (OR, 0.87 [95% CI, 0.78-0.97]) than the comparison cohort.
“We found overall, their pregnancies were just as healthy as those of the moms without MS,” Dr. Magyari said.
Comprehensive data
Denmark’s health care system has two key features that make it an attractive setting in which to conduct such a study – the first being its universal health care. The second advantage is that the country enacted several health registries in the 1970s and 1980s that enable the collection of more comprehensive data. For example, the Danish National Patient Register is a population-based registry that spans the entire nation, facilitating epidemiological research with what the study’s authors describe as “high generalizability.” Providing additional insights regarding the patient story helps add context to pregnancy and outcomes. Among the data collected on the women studied were demographics, contact information, and abortions, both spontaneous and medically induced. The country uses other databases and registries to capture additional data. For example, the Register of Legally Induced Abortions provides data regarding the context of medically induced abortions. In contrast, the Danish Medical Birth Registry provides context regarding specified variables regarding women’s pregnancies, delivery, and perinatal outcomes. Finally, the population’s education register offers information regarding patients’ educational history.
A key strength of this study is that the long duration of follow-up data from the Danish Medical Birth Registry, along with its comprehensive data collection, eliminates recall bias. Universal access to health care also improves the generalizability of data. A limitation of the study is its lack of data on maternal smoking and its effects on low gestational weights. The study also has some data gaps, including body mass index information missing from a large portion of the cohort. Finally, the sample size of newborns born to mothers who had received DMT therapy within the last 6 months of gestation was too underpowered to stratify based on first on first-line or second-line treatment.
Dr. Magyari served on scientific advisory boards for Biogen, Sanofi, Teva, Roche, Novartis, and Merck. She has also received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Teva, Roche, Merck, and Novartis. Coauthors disclosed various fees received from Merck, Novartis, Biogen, Roche, Sanofi Genzyme, and Teva.
, according to a new study published online Feb. 3 in Neurology Clinical Practice. While pregnancy and childbirth are not regarded as conditions that engender high-risk pregnancy in the MS population, previous studies evaluating the effects of MS on pregnancy and parturition have yet to fully elucidate some outcomes for pregnant women and their babies in multiple sclerosis.
“Women with multiple sclerosis may be understandably concerned about the risk of pregnancy,” said Melinda Magyari, MD, PhD, a consultant at the University of Copenhagen. “While previous research has shown there is no higher risk of birth defect for babies born to women with MS, we wanted to find out if women with MS are at risk for a variety of pregnancy complications.”
MS is regarded as a progressive, neurological disease mediated by the immune system that demands careful consideration of numerous situations and life changes including family planning. The MS population is overwhelmingly female, as women account for three out of every four cases of MS. The majority of these women range from 20 to 40 years of age at the time of being diagnosed with MS. Despite the unknown risks of pregnancy-related complications and various perinatal complications in this patient population, women who have MS are not discouraged from conceiving.
Assessing pregnancy outcomes
This nationwide, population-based, cross-sectional study evaluated the pregnancies of 2,930 women with MS between Jan. 1, 1997, and Dec. 31, 2016, registered in the Danish Multiple Sclerosis Registry. The researchers compared pregnancy-related and prenatal outcomes to a 5% random sample of 56,958 randomly-selected pregnant women from Denmark’s general population who did not have MS. They found no differences in the risks associated with several pregnancy-related complications (e.g., preeclampsia, gestational diabetes, or placental complications), emergency Cesarean section (C-section), instrumental delivery, stillbirth, preterm birth, or congenital malformation. Apgar scores were low in both groups. A composite of various biometrics in newborns such as reflexes, muscle tone, and heart rate immediately following birth, the Apgar score is used to help assess the neonatal health, with a value of less than 7 considered low. Here, preterm birth is defined as delivery occurring before 37 weeks of gestation, and stillbirth describes a fetus born dead after 22 weeks of gestation.
Women in the MS cohort were more likely to have elective C-sections (odds ratio, 2.89 [95% confidence interval, 1.65-2.16]), induced labor (OR, 1.15 [95%CI, 1.01-1.31]) and have babies with low birth weight based on their gestational age (OR, 1.29 [95% CI, 1.04-1.60]). Nearly 30% of babies born in the cohort (n = 851) were born to mothers who had received disease-modifying therapy (DMT). Neonates exposed to DMT weighed an average of 116 g less than babies born to mothers who had not received DMT (3,378 g vs. 3,494 g) with a slightly lower gestational age (39 weeks as opposed to 40 weeks). However, babies born to mothers with MS were less likely to show signs of asphyxia (OR, 0.87 [95% CI, 0.78-0.97]) than the comparison cohort.
“We found overall, their pregnancies were just as healthy as those of the moms without MS,” Dr. Magyari said.
Comprehensive data
Denmark’s health care system has two key features that make it an attractive setting in which to conduct such a study – the first being its universal health care. The second advantage is that the country enacted several health registries in the 1970s and 1980s that enable the collection of more comprehensive data. For example, the Danish National Patient Register is a population-based registry that spans the entire nation, facilitating epidemiological research with what the study’s authors describe as “high generalizability.” Providing additional insights regarding the patient story helps add context to pregnancy and outcomes. Among the data collected on the women studied were demographics, contact information, and abortions, both spontaneous and medically induced. The country uses other databases and registries to capture additional data. For example, the Register of Legally Induced Abortions provides data regarding the context of medically induced abortions. In contrast, the Danish Medical Birth Registry provides context regarding specified variables regarding women’s pregnancies, delivery, and perinatal outcomes. Finally, the population’s education register offers information regarding patients’ educational history.
A key strength of this study is that the long duration of follow-up data from the Danish Medical Birth Registry, along with its comprehensive data collection, eliminates recall bias. Universal access to health care also improves the generalizability of data. A limitation of the study is its lack of data on maternal smoking and its effects on low gestational weights. The study also has some data gaps, including body mass index information missing from a large portion of the cohort. Finally, the sample size of newborns born to mothers who had received DMT therapy within the last 6 months of gestation was too underpowered to stratify based on first on first-line or second-line treatment.
Dr. Magyari served on scientific advisory boards for Biogen, Sanofi, Teva, Roche, Novartis, and Merck. She has also received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Teva, Roche, Merck, and Novartis. Coauthors disclosed various fees received from Merck, Novartis, Biogen, Roche, Sanofi Genzyme, and Teva.
FROM NEUROLOGY CLINICAL PRACTICE
FDA approves intramuscular administration for peginterferon beta-1a in MS
“The new IM administration offers people living with relapsing MS the well-characterized efficacy and safety of Plegridy with the potential for significantly reduced injection site reactions,” Biogen said in a news release announcing the FDA action.
Plegridy is a pegylated version of interferon beta-1a, which prolongs the circulation time of the molecule in the body by increasing its size. The process extends the drug’s half-life, allowing for a less-frequent dosing schedule.
Peginterferon beta-1a administered subcutaneously was first approved by the FDA in 2014 based on data showing it significantly reduces MS relapses, disability progression, and brain lesions.
The FDA approved IM administration for peginterferon beta-1a based on data evaluating bioequivalence and adverse reactions associated with IM administration compared with subcutaneous (SC) administration in healthy volunteers.
Bioequivalence of the IM and SC dosing regimens was confirmed and volunteers receiving the drug through IM administration experienced fewer injection site reactions relative to those receiving SC administration (14.4% vs. 32.1%), the company said.
The overall safety profiles of IM and SC administration were generally similar, with no new safety signals.
The European Commission allowed marketing authorization for IM administration of peginterferon beta-1a in December 2020.
A version of this article first appeared on Medscape.com.
“The new IM administration offers people living with relapsing MS the well-characterized efficacy and safety of Plegridy with the potential for significantly reduced injection site reactions,” Biogen said in a news release announcing the FDA action.
Plegridy is a pegylated version of interferon beta-1a, which prolongs the circulation time of the molecule in the body by increasing its size. The process extends the drug’s half-life, allowing for a less-frequent dosing schedule.
Peginterferon beta-1a administered subcutaneously was first approved by the FDA in 2014 based on data showing it significantly reduces MS relapses, disability progression, and brain lesions.
The FDA approved IM administration for peginterferon beta-1a based on data evaluating bioequivalence and adverse reactions associated with IM administration compared with subcutaneous (SC) administration in healthy volunteers.
Bioequivalence of the IM and SC dosing regimens was confirmed and volunteers receiving the drug through IM administration experienced fewer injection site reactions relative to those receiving SC administration (14.4% vs. 32.1%), the company said.
The overall safety profiles of IM and SC administration were generally similar, with no new safety signals.
The European Commission allowed marketing authorization for IM administration of peginterferon beta-1a in December 2020.
A version of this article first appeared on Medscape.com.
“The new IM administration offers people living with relapsing MS the well-characterized efficacy and safety of Plegridy with the potential for significantly reduced injection site reactions,” Biogen said in a news release announcing the FDA action.
Plegridy is a pegylated version of interferon beta-1a, which prolongs the circulation time of the molecule in the body by increasing its size. The process extends the drug’s half-life, allowing for a less-frequent dosing schedule.
Peginterferon beta-1a administered subcutaneously was first approved by the FDA in 2014 based on data showing it significantly reduces MS relapses, disability progression, and brain lesions.
The FDA approved IM administration for peginterferon beta-1a based on data evaluating bioequivalence and adverse reactions associated with IM administration compared with subcutaneous (SC) administration in healthy volunteers.
Bioequivalence of the IM and SC dosing regimens was confirmed and volunteers receiving the drug through IM administration experienced fewer injection site reactions relative to those receiving SC administration (14.4% vs. 32.1%), the company said.
The overall safety profiles of IM and SC administration were generally similar, with no new safety signals.
The European Commission allowed marketing authorization for IM administration of peginterferon beta-1a in December 2020.
A version of this article first appeared on Medscape.com.
Is the EDSS an adequate outcome measure in secondary progressive MS trials?
Clinical trials enrolling patients with progressive multiple sclerosis (MS) commonly use the Expanded Disability Status Scale (EDSS), an instrument that looks at impairment across several different functional domains, as a primary outcome measure. But results from
For their research, published in the Jan. 5 issue of Neurology, Marcus W. Koch, MD, PhD, of the department of neurosciences at Hotchkiss Brain Institute at the University of Calgary (Alta.) and colleagues looked at data from the placebo arms of two randomized trials that collectively enrolled nearly 700 patients with secondary progressive MS (SPMS). The trials were similar in terms of baseline patient characteristics and level of disability.
Comparing three outcome measures
The investigators compared disability progression and improvement across each of the three instruments and their combinations. Because improvement is understood to occur only rarely in untreated secondary progressive MS, most improvement picked up in the placebo arm of a trial is assumed to be noise from random variation or measurement error.
Dr. Koch and colleagues found that the EDSS showed higher rates of improvement than the other tests. The EDSS also showed the smallest differences between progression and improvement among the three instruments, with improvement rate over time increasing in parallel with disability progression rates. With the other two tests, improvement rates remained low – at 10% or less – while disability was seen steadily increasing over time.
The results, the investigators wrote in their analysis, suggest that the timed 25-foot walk and 9-hole peg test are the more reliable outcome measures. The reason “may simply lie in the fact that both the timed 25-foot walk and 9-hole peg test are objective and quantitative interval-scaled measures while the EDSS is a graded categorical measure.” As primary outcome measures in clinical trials, “the lower noise of the timed 25-foot walk and 9-hole peg test may make them preferable over the EDSS,” Dr. Koch and colleagues concluded. The investigators noted that a 2019 analysis of different MS disability scales across more than 13,000 patients in 14 trials did not find such stark differences – but that the patients in the pooled trials had less disability at baseline (median EDSS score of 2.5, compared with 6.0 for the two trials in Dr. Koch and colleagues’ study). This suggests, the investigators wrote, “that the timed 25-foot walk and 9-hole peg test may be more useful outcomes in patients with a progressive disease course and with greater baseline disability.”
‘Considerable implications’ for the design of future clinical trials
In an accompanying editorial, Tomas Kalincik, MD, PhD, of the University of Melbourne, along with colleagues in Italy and Britain, praised Dr. Koch and colleagues’ study as having “considerable implications for the design of future clinical trials because detecting a treatment effect on an outcome that is subject to large measurement error is difficult.” Most trials in progressive MS use change in EDSS score as their primary or key secondary outcomes. “However, as the authors elegantly show, other, more reliable clinical outcomes are needed. As we are revisiting our biological hypotheses for treatment of progressive MS, perhaps the time has come that we should also revisit the instruments that we use to examine their efficacy.”
The editorialists allowed for the possibility that something besides noise or measurement error could be responsible for the disparities seen across the instruments. “An alternative interpretation of the presented results could be that recovery of neurologic function is more common in SPMS than what we had previously thought and that EDSS is more sensitive to its detection than the other two measures,” they wrote.
Dr. Koch and colleagues’ study received no outside funding. Dr. Koch disclosed consulting fees and other financial support from several drug manufacturers, and three coauthors also disclosed financial relationships with pharmaceutical companies. All three editorial writers disclosed similar relationships.
Clinical trials enrolling patients with progressive multiple sclerosis (MS) commonly use the Expanded Disability Status Scale (EDSS), an instrument that looks at impairment across several different functional domains, as a primary outcome measure. But results from
For their research, published in the Jan. 5 issue of Neurology, Marcus W. Koch, MD, PhD, of the department of neurosciences at Hotchkiss Brain Institute at the University of Calgary (Alta.) and colleagues looked at data from the placebo arms of two randomized trials that collectively enrolled nearly 700 patients with secondary progressive MS (SPMS). The trials were similar in terms of baseline patient characteristics and level of disability.
Comparing three outcome measures
The investigators compared disability progression and improvement across each of the three instruments and their combinations. Because improvement is understood to occur only rarely in untreated secondary progressive MS, most improvement picked up in the placebo arm of a trial is assumed to be noise from random variation or measurement error.
Dr. Koch and colleagues found that the EDSS showed higher rates of improvement than the other tests. The EDSS also showed the smallest differences between progression and improvement among the three instruments, with improvement rate over time increasing in parallel with disability progression rates. With the other two tests, improvement rates remained low – at 10% or less – while disability was seen steadily increasing over time.
The results, the investigators wrote in their analysis, suggest that the timed 25-foot walk and 9-hole peg test are the more reliable outcome measures. The reason “may simply lie in the fact that both the timed 25-foot walk and 9-hole peg test are objective and quantitative interval-scaled measures while the EDSS is a graded categorical measure.” As primary outcome measures in clinical trials, “the lower noise of the timed 25-foot walk and 9-hole peg test may make them preferable over the EDSS,” Dr. Koch and colleagues concluded. The investigators noted that a 2019 analysis of different MS disability scales across more than 13,000 patients in 14 trials did not find such stark differences – but that the patients in the pooled trials had less disability at baseline (median EDSS score of 2.5, compared with 6.0 for the two trials in Dr. Koch and colleagues’ study). This suggests, the investigators wrote, “that the timed 25-foot walk and 9-hole peg test may be more useful outcomes in patients with a progressive disease course and with greater baseline disability.”
‘Considerable implications’ for the design of future clinical trials
In an accompanying editorial, Tomas Kalincik, MD, PhD, of the University of Melbourne, along with colleagues in Italy and Britain, praised Dr. Koch and colleagues’ study as having “considerable implications for the design of future clinical trials because detecting a treatment effect on an outcome that is subject to large measurement error is difficult.” Most trials in progressive MS use change in EDSS score as their primary or key secondary outcomes. “However, as the authors elegantly show, other, more reliable clinical outcomes are needed. As we are revisiting our biological hypotheses for treatment of progressive MS, perhaps the time has come that we should also revisit the instruments that we use to examine their efficacy.”
The editorialists allowed for the possibility that something besides noise or measurement error could be responsible for the disparities seen across the instruments. “An alternative interpretation of the presented results could be that recovery of neurologic function is more common in SPMS than what we had previously thought and that EDSS is more sensitive to its detection than the other two measures,” they wrote.
Dr. Koch and colleagues’ study received no outside funding. Dr. Koch disclosed consulting fees and other financial support from several drug manufacturers, and three coauthors also disclosed financial relationships with pharmaceutical companies. All three editorial writers disclosed similar relationships.
Clinical trials enrolling patients with progressive multiple sclerosis (MS) commonly use the Expanded Disability Status Scale (EDSS), an instrument that looks at impairment across several different functional domains, as a primary outcome measure. But results from
For their research, published in the Jan. 5 issue of Neurology, Marcus W. Koch, MD, PhD, of the department of neurosciences at Hotchkiss Brain Institute at the University of Calgary (Alta.) and colleagues looked at data from the placebo arms of two randomized trials that collectively enrolled nearly 700 patients with secondary progressive MS (SPMS). The trials were similar in terms of baseline patient characteristics and level of disability.
Comparing three outcome measures
The investigators compared disability progression and improvement across each of the three instruments and their combinations. Because improvement is understood to occur only rarely in untreated secondary progressive MS, most improvement picked up in the placebo arm of a trial is assumed to be noise from random variation or measurement error.
Dr. Koch and colleagues found that the EDSS showed higher rates of improvement than the other tests. The EDSS also showed the smallest differences between progression and improvement among the three instruments, with improvement rate over time increasing in parallel with disability progression rates. With the other two tests, improvement rates remained low – at 10% or less – while disability was seen steadily increasing over time.
The results, the investigators wrote in their analysis, suggest that the timed 25-foot walk and 9-hole peg test are the more reliable outcome measures. The reason “may simply lie in the fact that both the timed 25-foot walk and 9-hole peg test are objective and quantitative interval-scaled measures while the EDSS is a graded categorical measure.” As primary outcome measures in clinical trials, “the lower noise of the timed 25-foot walk and 9-hole peg test may make them preferable over the EDSS,” Dr. Koch and colleagues concluded. The investigators noted that a 2019 analysis of different MS disability scales across more than 13,000 patients in 14 trials did not find such stark differences – but that the patients in the pooled trials had less disability at baseline (median EDSS score of 2.5, compared with 6.0 for the two trials in Dr. Koch and colleagues’ study). This suggests, the investigators wrote, “that the timed 25-foot walk and 9-hole peg test may be more useful outcomes in patients with a progressive disease course and with greater baseline disability.”
‘Considerable implications’ for the design of future clinical trials
In an accompanying editorial, Tomas Kalincik, MD, PhD, of the University of Melbourne, along with colleagues in Italy and Britain, praised Dr. Koch and colleagues’ study as having “considerable implications for the design of future clinical trials because detecting a treatment effect on an outcome that is subject to large measurement error is difficult.” Most trials in progressive MS use change in EDSS score as their primary or key secondary outcomes. “However, as the authors elegantly show, other, more reliable clinical outcomes are needed. As we are revisiting our biological hypotheses for treatment of progressive MS, perhaps the time has come that we should also revisit the instruments that we use to examine their efficacy.”
The editorialists allowed for the possibility that something besides noise or measurement error could be responsible for the disparities seen across the instruments. “An alternative interpretation of the presented results could be that recovery of neurologic function is more common in SPMS than what we had previously thought and that EDSS is more sensitive to its detection than the other two measures,” they wrote.
Dr. Koch and colleagues’ study received no outside funding. Dr. Koch disclosed consulting fees and other financial support from several drug manufacturers, and three coauthors also disclosed financial relationships with pharmaceutical companies. All three editorial writers disclosed similar relationships.
FROM NEUROLOGY
Stem cell transplant shows long-term benefit in MS
The benefits of autologous hematopoietic stem cell transplant (AHSCT) for patients with multiple sclerosis (MS) persist for more than 10 years in the majority of patents, new data show. The study reports on 210 Italian patients who underwent AHSCT between 2007 and 2019. Among the entire study cohort, 79.5% of patients had not experienced worsening of disability at 5 years, and 65.5% had not experienced it at 10 years.
Patients with relapsing remitting MS had better results, with 85.5% experiencing no worsening of disability at 5 years, and 71.3% at 10 years. Among patients with progressive MS, 71.0% showed no worsening of disability at 5 years, and 57.2% at 10 years.
“This is the longest follow-up of AHSCT in MS patients so far to be reported,” said study author Matilde Inglese, MD, University of Genoa (Italy). “We have shown AHSCT to be highly effective to prevent long-term disability worsening in most treated patients.”
The study was published online Jan. 20 in Neurology.
“We suggest that AHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” the authors concluded.
The study had no control group, so a direct comparison is not possible. Nevertheless, Dr. Inglese said she believed these results are better than those that would be achieved with disease-modifying drug therapy for similar patients.
“The best patient candidates for this procedure are those with highly active multiple sclerosis who are not responsive to high-efficacy drugs, such as alemtuzumab or ocrelizumab,” Dr. Inglese commented. “Younger patients with an aggressive form of relapsing remitting MS tend to do the best, although patients with progressive forms of MS who still have active lesions on MRI also benefit.”
Renewing the immune system
The transplant procedure involves giving high-dose cyclophosphamide to stimulate mobilization of bone marrow stem cells, which are collected from peripheral blood. Patients then undergo intense immunosuppression with a cocktail of drugs to remove the autoreactive T cells, and the stem cells, which are not autoreactive, are reinfused.
“We are effectively renewing the immune system,” Dr. Inglese said. “While it is not correct to call it a cure, as we are not eliminating the etiology of the disease, it is the closest to complete suppression of the disease that we can get.”
Other results from the study show that among patients with relapsing remitting MS, rates of relapse-free survival were 78.1% at 5 years and 63.5% at 10 years.
Better results were achieved for patients who received the BEAM+ATG conditioning regimen for immunosuppression. That regimen includes carmustine, cytosine-arabinoside, etoposide, and melphalan, followed by rabbit antithymocyte globulin. Among patients with relapsing remitting disease who were treated with this protocol, rates of relapse-free survival were 86.4% at 5 years and 77.0% at 10 years.
For patients with relapsing remitting MS, the probability of achieving NEDA-3 status (no evidence of disease activity, including the absence of clinical relapses, disability worsening, and MRI inflammatory activity) was 62.2% at 5 years and 40.5% at 10 years.
Among those patients with relapsing remitting MS who received the BEAM+ATG conditioning protocol, NEDA-3 status was achieved in 67.7% at 5 years and in 54.9% at 10 years.
Three deaths occurred within 100 days following AHSCT (1.4% of the entire study population). One patient developed pulmonary thromboembolism, received fibrinolytic treatment, and died 48 hours later after intracranial hemorrhage. The second patient experienced engraftment failure and died 24 days after transplant because of an opportunistic infection. The third patient died 1 month after transplant from Wernicke-like encephalopathy. All the patients who died received the BEAM+ATG conditioning regimen. No transplant-related deaths occurred in patients who underwent transplant after 2007.
Dr. Inglese noted that the mortality rate associated with AHSCT has been greatly reduced in recent years. “We are seeing a very low mortality rate – about 0.3% – thanks to improvements in the procedure and better patient selection. This seems acceptable, given that we are treating patients with very aggressive disease who have a high risk of becoming significantly disabled relatively early in life,” she commented.
However, it is vitally important that the procedure be conducted in a specialized center with a highly experienced multidisciplinary team, she stressed.
In the Neurology article, the authors concluded: “Although patients with RRMS [relapsing remitting MS] are those who benefit the most from transplant, AHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS.
“The BEAM+ATG conditioning protocol, although associated with a higher transplant mortality rate, was associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity, allowing complete disease control in a higher proportion of patients,” they wrote.
Potent and durable efficacy, with caveats
Commenting on these latest findings, Jeffrey A. Cohen, MD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said: “AHSCT appears to have potent and durable efficacy in MS but is associated with significant risk and cost.”
The patients who are most likely to benefit are young and have experienced the onset of disease relatively recently. They are still ambulatory with highly active MS and have experienced recent clinical relapses and/or MRI lesion activity, and such activity continues despite disease-modifying therapy, Dr. Cohen noted. He added that “AHSCT is a reasonable option for such patients who have essentially failed the available disease-modifying therapy options.”
He pointed out that the key question is where AHSCT belongs in the overall MS algorithm relative to other high-efficacy therapies. “We need to know whether it should be used more broadly rather than as a last resort.”
To address that question, several randomized trials comparing AHSCT with high-efficacy disease-modifying therapy are in progress, including the National Institutes of Health–sponsored BEAT-MS trial in the United States (for which Dr. Cohen is the lead investigator) and four European trials – NET-MS (for which Dr. Inglese is the lead investigator), STAR-MS, RAM-MS, and COAST-MS.
The current study was partially funded and supported by the Italian Multiple Sclerosis Foundation. Dr. Inglese disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The benefits of autologous hematopoietic stem cell transplant (AHSCT) for patients with multiple sclerosis (MS) persist for more than 10 years in the majority of patents, new data show. The study reports on 210 Italian patients who underwent AHSCT between 2007 and 2019. Among the entire study cohort, 79.5% of patients had not experienced worsening of disability at 5 years, and 65.5% had not experienced it at 10 years.
Patients with relapsing remitting MS had better results, with 85.5% experiencing no worsening of disability at 5 years, and 71.3% at 10 years. Among patients with progressive MS, 71.0% showed no worsening of disability at 5 years, and 57.2% at 10 years.
“This is the longest follow-up of AHSCT in MS patients so far to be reported,” said study author Matilde Inglese, MD, University of Genoa (Italy). “We have shown AHSCT to be highly effective to prevent long-term disability worsening in most treated patients.”
The study was published online Jan. 20 in Neurology.
“We suggest that AHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” the authors concluded.
The study had no control group, so a direct comparison is not possible. Nevertheless, Dr. Inglese said she believed these results are better than those that would be achieved with disease-modifying drug therapy for similar patients.
“The best patient candidates for this procedure are those with highly active multiple sclerosis who are not responsive to high-efficacy drugs, such as alemtuzumab or ocrelizumab,” Dr. Inglese commented. “Younger patients with an aggressive form of relapsing remitting MS tend to do the best, although patients with progressive forms of MS who still have active lesions on MRI also benefit.”
Renewing the immune system
The transplant procedure involves giving high-dose cyclophosphamide to stimulate mobilization of bone marrow stem cells, which are collected from peripheral blood. Patients then undergo intense immunosuppression with a cocktail of drugs to remove the autoreactive T cells, and the stem cells, which are not autoreactive, are reinfused.
“We are effectively renewing the immune system,” Dr. Inglese said. “While it is not correct to call it a cure, as we are not eliminating the etiology of the disease, it is the closest to complete suppression of the disease that we can get.”
Other results from the study show that among patients with relapsing remitting MS, rates of relapse-free survival were 78.1% at 5 years and 63.5% at 10 years.
Better results were achieved for patients who received the BEAM+ATG conditioning regimen for immunosuppression. That regimen includes carmustine, cytosine-arabinoside, etoposide, and melphalan, followed by rabbit antithymocyte globulin. Among patients with relapsing remitting disease who were treated with this protocol, rates of relapse-free survival were 86.4% at 5 years and 77.0% at 10 years.
For patients with relapsing remitting MS, the probability of achieving NEDA-3 status (no evidence of disease activity, including the absence of clinical relapses, disability worsening, and MRI inflammatory activity) was 62.2% at 5 years and 40.5% at 10 years.
Among those patients with relapsing remitting MS who received the BEAM+ATG conditioning protocol, NEDA-3 status was achieved in 67.7% at 5 years and in 54.9% at 10 years.
Three deaths occurred within 100 days following AHSCT (1.4% of the entire study population). One patient developed pulmonary thromboembolism, received fibrinolytic treatment, and died 48 hours later after intracranial hemorrhage. The second patient experienced engraftment failure and died 24 days after transplant because of an opportunistic infection. The third patient died 1 month after transplant from Wernicke-like encephalopathy. All the patients who died received the BEAM+ATG conditioning regimen. No transplant-related deaths occurred in patients who underwent transplant after 2007.
Dr. Inglese noted that the mortality rate associated with AHSCT has been greatly reduced in recent years. “We are seeing a very low mortality rate – about 0.3% – thanks to improvements in the procedure and better patient selection. This seems acceptable, given that we are treating patients with very aggressive disease who have a high risk of becoming significantly disabled relatively early in life,” she commented.
However, it is vitally important that the procedure be conducted in a specialized center with a highly experienced multidisciplinary team, she stressed.
In the Neurology article, the authors concluded: “Although patients with RRMS [relapsing remitting MS] are those who benefit the most from transplant, AHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS.
“The BEAM+ATG conditioning protocol, although associated with a higher transplant mortality rate, was associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity, allowing complete disease control in a higher proportion of patients,” they wrote.
Potent and durable efficacy, with caveats
Commenting on these latest findings, Jeffrey A. Cohen, MD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said: “AHSCT appears to have potent and durable efficacy in MS but is associated with significant risk and cost.”
The patients who are most likely to benefit are young and have experienced the onset of disease relatively recently. They are still ambulatory with highly active MS and have experienced recent clinical relapses and/or MRI lesion activity, and such activity continues despite disease-modifying therapy, Dr. Cohen noted. He added that “AHSCT is a reasonable option for such patients who have essentially failed the available disease-modifying therapy options.”
He pointed out that the key question is where AHSCT belongs in the overall MS algorithm relative to other high-efficacy therapies. “We need to know whether it should be used more broadly rather than as a last resort.”
To address that question, several randomized trials comparing AHSCT with high-efficacy disease-modifying therapy are in progress, including the National Institutes of Health–sponsored BEAT-MS trial in the United States (for which Dr. Cohen is the lead investigator) and four European trials – NET-MS (for which Dr. Inglese is the lead investigator), STAR-MS, RAM-MS, and COAST-MS.
The current study was partially funded and supported by the Italian Multiple Sclerosis Foundation. Dr. Inglese disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The benefits of autologous hematopoietic stem cell transplant (AHSCT) for patients with multiple sclerosis (MS) persist for more than 10 years in the majority of patents, new data show. The study reports on 210 Italian patients who underwent AHSCT between 2007 and 2019. Among the entire study cohort, 79.5% of patients had not experienced worsening of disability at 5 years, and 65.5% had not experienced it at 10 years.
Patients with relapsing remitting MS had better results, with 85.5% experiencing no worsening of disability at 5 years, and 71.3% at 10 years. Among patients with progressive MS, 71.0% showed no worsening of disability at 5 years, and 57.2% at 10 years.
“This is the longest follow-up of AHSCT in MS patients so far to be reported,” said study author Matilde Inglese, MD, University of Genoa (Italy). “We have shown AHSCT to be highly effective to prevent long-term disability worsening in most treated patients.”
The study was published online Jan. 20 in Neurology.
“We suggest that AHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” the authors concluded.
The study had no control group, so a direct comparison is not possible. Nevertheless, Dr. Inglese said she believed these results are better than those that would be achieved with disease-modifying drug therapy for similar patients.
“The best patient candidates for this procedure are those with highly active multiple sclerosis who are not responsive to high-efficacy drugs, such as alemtuzumab or ocrelizumab,” Dr. Inglese commented. “Younger patients with an aggressive form of relapsing remitting MS tend to do the best, although patients with progressive forms of MS who still have active lesions on MRI also benefit.”
Renewing the immune system
The transplant procedure involves giving high-dose cyclophosphamide to stimulate mobilization of bone marrow stem cells, which are collected from peripheral blood. Patients then undergo intense immunosuppression with a cocktail of drugs to remove the autoreactive T cells, and the stem cells, which are not autoreactive, are reinfused.
“We are effectively renewing the immune system,” Dr. Inglese said. “While it is not correct to call it a cure, as we are not eliminating the etiology of the disease, it is the closest to complete suppression of the disease that we can get.”
Other results from the study show that among patients with relapsing remitting MS, rates of relapse-free survival were 78.1% at 5 years and 63.5% at 10 years.
Better results were achieved for patients who received the BEAM+ATG conditioning regimen for immunosuppression. That regimen includes carmustine, cytosine-arabinoside, etoposide, and melphalan, followed by rabbit antithymocyte globulin. Among patients with relapsing remitting disease who were treated with this protocol, rates of relapse-free survival were 86.4% at 5 years and 77.0% at 10 years.
For patients with relapsing remitting MS, the probability of achieving NEDA-3 status (no evidence of disease activity, including the absence of clinical relapses, disability worsening, and MRI inflammatory activity) was 62.2% at 5 years and 40.5% at 10 years.
Among those patients with relapsing remitting MS who received the BEAM+ATG conditioning protocol, NEDA-3 status was achieved in 67.7% at 5 years and in 54.9% at 10 years.
Three deaths occurred within 100 days following AHSCT (1.4% of the entire study population). One patient developed pulmonary thromboembolism, received fibrinolytic treatment, and died 48 hours later after intracranial hemorrhage. The second patient experienced engraftment failure and died 24 days after transplant because of an opportunistic infection. The third patient died 1 month after transplant from Wernicke-like encephalopathy. All the patients who died received the BEAM+ATG conditioning regimen. No transplant-related deaths occurred in patients who underwent transplant after 2007.
Dr. Inglese noted that the mortality rate associated with AHSCT has been greatly reduced in recent years. “We are seeing a very low mortality rate – about 0.3% – thanks to improvements in the procedure and better patient selection. This seems acceptable, given that we are treating patients with very aggressive disease who have a high risk of becoming significantly disabled relatively early in life,” she commented.
However, it is vitally important that the procedure be conducted in a specialized center with a highly experienced multidisciplinary team, she stressed.
In the Neurology article, the authors concluded: “Although patients with RRMS [relapsing remitting MS] are those who benefit the most from transplant, AHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS.
“The BEAM+ATG conditioning protocol, although associated with a higher transplant mortality rate, was associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity, allowing complete disease control in a higher proportion of patients,” they wrote.
Potent and durable efficacy, with caveats
Commenting on these latest findings, Jeffrey A. Cohen, MD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said: “AHSCT appears to have potent and durable efficacy in MS but is associated with significant risk and cost.”
The patients who are most likely to benefit are young and have experienced the onset of disease relatively recently. They are still ambulatory with highly active MS and have experienced recent clinical relapses and/or MRI lesion activity, and such activity continues despite disease-modifying therapy, Dr. Cohen noted. He added that “AHSCT is a reasonable option for such patients who have essentially failed the available disease-modifying therapy options.”
He pointed out that the key question is where AHSCT belongs in the overall MS algorithm relative to other high-efficacy therapies. “We need to know whether it should be used more broadly rather than as a last resort.”
To address that question, several randomized trials comparing AHSCT with high-efficacy disease-modifying therapy are in progress, including the National Institutes of Health–sponsored BEAT-MS trial in the United States (for which Dr. Cohen is the lead investigator) and four European trials – NET-MS (for which Dr. Inglese is the lead investigator), STAR-MS, RAM-MS, and COAST-MS.
The current study was partially funded and supported by the Italian Multiple Sclerosis Foundation. Dr. Inglese disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY