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Serious complications linked to rituximab in MS
NASHVILLE, TENN. – In a sign of the potential complications that can be spawned by B-cell–depleting therapies, a new report found that 5 of 30 patients with relapsing-remitting multiple sclerosis (RRMS) had to discontinue or interrupt long-term treatment with rituximab (Rituxan) because of serious infections such as pneumonia, septic arthritis, and sinusitis.
The findings are a “big lesson to not just focus on opportunistic infections [with Rituxan use] but also consider nonopportunistic infections that could occur,” lead study author Cindy Darius, a registered nurse with the Johns Hopkins Multiple Sclerosis Center (JHMSC), Baltimore, said in an interview. She presented the research at the annual meeting of the Consortium of Multiple Sclerosis Centers.
As Ms. Darius noted, progressive multifocal leukoencephalopathy has been the main focus of discussions about the use of rituximab in MS, as the disease has been noted in patients who have taken rituximab for other conditions.
But Ms. Darius said that the JHMSC observed a trend of patients with MS who took rituximab and developed “these weird infections that were more nonopportunistic infections. That prompted us to dig a little bit deeper: Are these infections happening sporadically, or could they have a connection with Rituxan?”
Ms. Darius and her colleagues retrospectively reviewed the records of 30 patients with MS who were prescribed rituximab by a single JHMSC physician since 2012. They found five cases of infectious complications, all in patients with RRMS:
- A woman, aged 30 years, whose rituximab regimen was interrupted after 4 years of treatment when she developed recurrent pneumonia.
- A man, aged 42 years, who took rituximab for a year then stopped after developing ringworm and two bouts of Staphylococcus aureus septic arthritis, and who had previously changed from natalizumab (Tysabri) to rituximab after seroconverting to the John Cunningham virus.
- A woman, aged 65 years, with Sjögren’s syndrome who stopped rituximab at 2 years after developing sinusitis, pneumonia, and herpes simplex virus keratitis.
- A woman, aged 38 years, who discontinued rituximab after 2 years because of recurrent urosepsis, sinusitis, and pyrexia of unknown origin.
- A woman, aged 56 years, who stopped rituximab after 2 years following intractable sinusitis and pneumonia that resulted in empyema and required a thoracotomy.
What might be causing the apparent side effects? Ms. Darius pointed out that the patients were already immunocompromised because of previous treatment with first- and/or second-line medications. She added that the complications “may be due to dosing that may be a little too high for the MS population.”
JHMSC is considering whether to give doses of the drug once a year instead of twice annually, she said. “Other providers are cutting the dose in half: Instead of 1,000 mg, they’re giving 500,” she added. “After the patient has been on the medication for a year or two, and you feel the disease process has stabilized, you may want to consider adjusting the dosage.”
Going forward, the researchers wrote that they “plan to determine the incidence of all serious infectious complications related to rituximab use among MS patients attending the JHMSC, and the influence of different dosing protocols between MS providers in this regard.”
No study funding was reported, and most study authors reported no relevant disclosures. One author reported receiving National Institutes of Health funding and another reported consulting for Biogen and Genentech.
SOURCE: Darius C et al. CMSC 2018, Abstract DX57.
NASHVILLE, TENN. – In a sign of the potential complications that can be spawned by B-cell–depleting therapies, a new report found that 5 of 30 patients with relapsing-remitting multiple sclerosis (RRMS) had to discontinue or interrupt long-term treatment with rituximab (Rituxan) because of serious infections such as pneumonia, septic arthritis, and sinusitis.
The findings are a “big lesson to not just focus on opportunistic infections [with Rituxan use] but also consider nonopportunistic infections that could occur,” lead study author Cindy Darius, a registered nurse with the Johns Hopkins Multiple Sclerosis Center (JHMSC), Baltimore, said in an interview. She presented the research at the annual meeting of the Consortium of Multiple Sclerosis Centers.
As Ms. Darius noted, progressive multifocal leukoencephalopathy has been the main focus of discussions about the use of rituximab in MS, as the disease has been noted in patients who have taken rituximab for other conditions.
But Ms. Darius said that the JHMSC observed a trend of patients with MS who took rituximab and developed “these weird infections that were more nonopportunistic infections. That prompted us to dig a little bit deeper: Are these infections happening sporadically, or could they have a connection with Rituxan?”
Ms. Darius and her colleagues retrospectively reviewed the records of 30 patients with MS who were prescribed rituximab by a single JHMSC physician since 2012. They found five cases of infectious complications, all in patients with RRMS:
- A woman, aged 30 years, whose rituximab regimen was interrupted after 4 years of treatment when she developed recurrent pneumonia.
- A man, aged 42 years, who took rituximab for a year then stopped after developing ringworm and two bouts of Staphylococcus aureus septic arthritis, and who had previously changed from natalizumab (Tysabri) to rituximab after seroconverting to the John Cunningham virus.
- A woman, aged 65 years, with Sjögren’s syndrome who stopped rituximab at 2 years after developing sinusitis, pneumonia, and herpes simplex virus keratitis.
- A woman, aged 38 years, who discontinued rituximab after 2 years because of recurrent urosepsis, sinusitis, and pyrexia of unknown origin.
- A woman, aged 56 years, who stopped rituximab after 2 years following intractable sinusitis and pneumonia that resulted in empyema and required a thoracotomy.
What might be causing the apparent side effects? Ms. Darius pointed out that the patients were already immunocompromised because of previous treatment with first- and/or second-line medications. She added that the complications “may be due to dosing that may be a little too high for the MS population.”
JHMSC is considering whether to give doses of the drug once a year instead of twice annually, she said. “Other providers are cutting the dose in half: Instead of 1,000 mg, they’re giving 500,” she added. “After the patient has been on the medication for a year or two, and you feel the disease process has stabilized, you may want to consider adjusting the dosage.”
Going forward, the researchers wrote that they “plan to determine the incidence of all serious infectious complications related to rituximab use among MS patients attending the JHMSC, and the influence of different dosing protocols between MS providers in this regard.”
No study funding was reported, and most study authors reported no relevant disclosures. One author reported receiving National Institutes of Health funding and another reported consulting for Biogen and Genentech.
SOURCE: Darius C et al. CMSC 2018, Abstract DX57.
NASHVILLE, TENN. – In a sign of the potential complications that can be spawned by B-cell–depleting therapies, a new report found that 5 of 30 patients with relapsing-remitting multiple sclerosis (RRMS) had to discontinue or interrupt long-term treatment with rituximab (Rituxan) because of serious infections such as pneumonia, septic arthritis, and sinusitis.
The findings are a “big lesson to not just focus on opportunistic infections [with Rituxan use] but also consider nonopportunistic infections that could occur,” lead study author Cindy Darius, a registered nurse with the Johns Hopkins Multiple Sclerosis Center (JHMSC), Baltimore, said in an interview. She presented the research at the annual meeting of the Consortium of Multiple Sclerosis Centers.
As Ms. Darius noted, progressive multifocal leukoencephalopathy has been the main focus of discussions about the use of rituximab in MS, as the disease has been noted in patients who have taken rituximab for other conditions.
But Ms. Darius said that the JHMSC observed a trend of patients with MS who took rituximab and developed “these weird infections that were more nonopportunistic infections. That prompted us to dig a little bit deeper: Are these infections happening sporadically, or could they have a connection with Rituxan?”
Ms. Darius and her colleagues retrospectively reviewed the records of 30 patients with MS who were prescribed rituximab by a single JHMSC physician since 2012. They found five cases of infectious complications, all in patients with RRMS:
- A woman, aged 30 years, whose rituximab regimen was interrupted after 4 years of treatment when she developed recurrent pneumonia.
- A man, aged 42 years, who took rituximab for a year then stopped after developing ringworm and two bouts of Staphylococcus aureus septic arthritis, and who had previously changed from natalizumab (Tysabri) to rituximab after seroconverting to the John Cunningham virus.
- A woman, aged 65 years, with Sjögren’s syndrome who stopped rituximab at 2 years after developing sinusitis, pneumonia, and herpes simplex virus keratitis.
- A woman, aged 38 years, who discontinued rituximab after 2 years because of recurrent urosepsis, sinusitis, and pyrexia of unknown origin.
- A woman, aged 56 years, who stopped rituximab after 2 years following intractable sinusitis and pneumonia that resulted in empyema and required a thoracotomy.
What might be causing the apparent side effects? Ms. Darius pointed out that the patients were already immunocompromised because of previous treatment with first- and/or second-line medications. She added that the complications “may be due to dosing that may be a little too high for the MS population.”
JHMSC is considering whether to give doses of the drug once a year instead of twice annually, she said. “Other providers are cutting the dose in half: Instead of 1,000 mg, they’re giving 500,” she added. “After the patient has been on the medication for a year or two, and you feel the disease process has stabilized, you may want to consider adjusting the dosage.”
Going forward, the researchers wrote that they “plan to determine the incidence of all serious infectious complications related to rituximab use among MS patients attending the JHMSC, and the influence of different dosing protocols between MS providers in this regard.”
No study funding was reported, and most study authors reported no relevant disclosures. One author reported receiving National Institutes of Health funding and another reported consulting for Biogen and Genentech.
SOURCE: Darius C et al. CMSC 2018, Abstract DX57.
REPORTING FROM THE CMSC ANNUAL MEETING
Key clinical point: Much of the attention toward side effects in rituximab as an off-label treatment for multiple sclerosis has focused on progressive multifocal leukoencephalopathy, but other infections may affect this population over the long term.
Major finding: Of 30 patients treated with rituximab for MS, 5 developed infections that required suspension or cessation of the treatment.
Study details: A retrospective analysis of 30 patients with MS treated with rituximab since 2012.
Disclosures: No study funding was reported, and most study authors reported no relevant disclosures. One author reported receiving National Institutes of Health funding and another reported consulting for Biogen and Genentech.
Source: Darius C et al. CMSC 2018, Abstract DX57.
Take precautions as cancer picture in MS remains hazy
NASHVILLE, TENN. – With much unknown about the risks of cancer and vaccination associated with immunosuppressants used in multiple sclerosis treatment, a neurologist advised colleagues to be aware of the potential dangers and take appropriate precautions.
For example, Eric Williamson, MD, of the University of Pennsylvania and Philadelphia Veterans Administration Hospital, said he goes a step further than recommending that adult female patients with MS who take ocrelizumab (Ocrevus) get regular mammograms. Per policy, he also double-checks to make sure that patients actually get screened.
“I know two women who were diagnosed with breast cancer before they began on their treatment because we asked about mammograms,” said Dr. Williamson, who spoke in a presentation about the risks of immunosuppressants in MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.
In regard to cancer as a whole, he said, “it’s unclear if there is any true increased risk in MS patients.” But this doesn’t mean there is no danger, he said, since research into immunosuppressants in other contexts show that they can boost the risk of cancer by three times to as much as several hundred times.
In transplant patients, he said, immunosuppressants are linked to higher rates of lymphoproliferative tumors (such as those linked to Epstein-Barr virus), Kaposi sarcoma, and cutaneous, renal, hepatobiliary, and anogenital tumors.
Research is also hazy in regard to specific immunosuppressants used to treat MS. Two reports published about a decade ago raised the possibility that natalizumab (Tysabri) may have sparked a slightly higher risk cancer in patients taking the drug for Crohn’s disease and MS, respectively; the latter report hinted at a higher risk of melanoma specifically. However, Dr. Williamson said postmarketing surveillance has not detected any further sign of trouble (N Engl J Med. 2006;354:899‐910; N Engl J Med. 2008;358;647‐8).
Another drug, ocrelizumab (Ocrevus), has sparked questions about a possible breast cancer risk. As Genentech, its manufacturer, notes: “breast cancer occurred in 6 of 781 females treated with Ocrevus and none of 668 females treated with Rebif [interferon beta-1a] or placebo.”
However, a researcher reported ocrelizumab open-label extension study data at the 2017 CMSC annual meeting and said, “incidence rates of malignancies and breast cancer observed with ocrelizumab treatment in MS remain within the range of epidemiologic background data.”
For now, Dr. Williamson, said, it may take decades to understand if there’s actually an increased breast cancer risk with ocrelizumab.
Skin cancer is a concern for fingolimod (Gilenya), Dr. Williamson said, specifically basal cell carcinoma and melanoma. It’s debatable whether patients should be required to see a dermatologist or make annual visits, he said. Per policy, his VA employer requires these patients to visit a dermatologist.
Whatever the case, it’s important to keep in mind that skin cancer screenings are advisable in general, he said.
Guidance on vaccinations
On the vaccination front, Dr. Williamson said vaccines are a good idea for MS patients – as long as they’re “relatively safe” – because some infectious diseases appear to be more severe in this population.
Flu is a special danger, Dr. Williamson said. He recommends the flu vaccine to patients “because people with MS are at higher risk of influenza-related complications or hospitalizations.”
With guidance from a report led by Dr. Williamson, the National Multiple Sclerosis Society offers recommendations about whether patients with MS should use various vaccines (Curr Neurol Neurosci Rep. 2016;16:36).
Dr. Williamson cautioned that patients with MS who take dimethyl fumarate (Tecfidera), ocrelizumab (Ocrevus), and fingolimod (Gilenya) should not use live vaccines. The drugs can pose issues in regard to other vaccines, too, he said (Plos ONE 2013; 8:e78532; Neurol Res 2012;34:730-3; Neurology. 2013;81:552-8).
Autoimmune risk with alemtuzumab
Alemtuzumab (Lemtrada) has been linked to autoimmune thyroid disorders, especially Graves’ disease, Dr. Williamson said. It’s estimated to affect 17%-41% of patients (Front Endocrinol [Lausanne]. 2017;8:254).
Potentially life-threatening idiopathic thrombocytopenic purpura occurs in 2% of patients on Lemtrada, he said, and anti-GMB nephropathy/Goodpasture’s syndrome has been reported in 0.1%.
Dr. Williamson also noted case reports of autoimmune hemolytic anemia and hepatitis. Earlier this year, three reports in Neurology noted acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients (Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422, doi: 10.1212/WNL.0000000000005420, doi: 10.1212/WNL.0000000000005417).
Dr. Williamson disclosed past consulting for Bayer, Biogen, Celgene, Genentech, EMD Serono, Teva, and Novartis, and current research support from Actelion and Alexion.
NASHVILLE, TENN. – With much unknown about the risks of cancer and vaccination associated with immunosuppressants used in multiple sclerosis treatment, a neurologist advised colleagues to be aware of the potential dangers and take appropriate precautions.
For example, Eric Williamson, MD, of the University of Pennsylvania and Philadelphia Veterans Administration Hospital, said he goes a step further than recommending that adult female patients with MS who take ocrelizumab (Ocrevus) get regular mammograms. Per policy, he also double-checks to make sure that patients actually get screened.
“I know two women who were diagnosed with breast cancer before they began on their treatment because we asked about mammograms,” said Dr. Williamson, who spoke in a presentation about the risks of immunosuppressants in MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.
In regard to cancer as a whole, he said, “it’s unclear if there is any true increased risk in MS patients.” But this doesn’t mean there is no danger, he said, since research into immunosuppressants in other contexts show that they can boost the risk of cancer by three times to as much as several hundred times.
In transplant patients, he said, immunosuppressants are linked to higher rates of lymphoproliferative tumors (such as those linked to Epstein-Barr virus), Kaposi sarcoma, and cutaneous, renal, hepatobiliary, and anogenital tumors.
Research is also hazy in regard to specific immunosuppressants used to treat MS. Two reports published about a decade ago raised the possibility that natalizumab (Tysabri) may have sparked a slightly higher risk cancer in patients taking the drug for Crohn’s disease and MS, respectively; the latter report hinted at a higher risk of melanoma specifically. However, Dr. Williamson said postmarketing surveillance has not detected any further sign of trouble (N Engl J Med. 2006;354:899‐910; N Engl J Med. 2008;358;647‐8).
Another drug, ocrelizumab (Ocrevus), has sparked questions about a possible breast cancer risk. As Genentech, its manufacturer, notes: “breast cancer occurred in 6 of 781 females treated with Ocrevus and none of 668 females treated with Rebif [interferon beta-1a] or placebo.”
However, a researcher reported ocrelizumab open-label extension study data at the 2017 CMSC annual meeting and said, “incidence rates of malignancies and breast cancer observed with ocrelizumab treatment in MS remain within the range of epidemiologic background data.”
For now, Dr. Williamson, said, it may take decades to understand if there’s actually an increased breast cancer risk with ocrelizumab.
Skin cancer is a concern for fingolimod (Gilenya), Dr. Williamson said, specifically basal cell carcinoma and melanoma. It’s debatable whether patients should be required to see a dermatologist or make annual visits, he said. Per policy, his VA employer requires these patients to visit a dermatologist.
Whatever the case, it’s important to keep in mind that skin cancer screenings are advisable in general, he said.
Guidance on vaccinations
On the vaccination front, Dr. Williamson said vaccines are a good idea for MS patients – as long as they’re “relatively safe” – because some infectious diseases appear to be more severe in this population.
Flu is a special danger, Dr. Williamson said. He recommends the flu vaccine to patients “because people with MS are at higher risk of influenza-related complications or hospitalizations.”
With guidance from a report led by Dr. Williamson, the National Multiple Sclerosis Society offers recommendations about whether patients with MS should use various vaccines (Curr Neurol Neurosci Rep. 2016;16:36).
Dr. Williamson cautioned that patients with MS who take dimethyl fumarate (Tecfidera), ocrelizumab (Ocrevus), and fingolimod (Gilenya) should not use live vaccines. The drugs can pose issues in regard to other vaccines, too, he said (Plos ONE 2013; 8:e78532; Neurol Res 2012;34:730-3; Neurology. 2013;81:552-8).
Autoimmune risk with alemtuzumab
Alemtuzumab (Lemtrada) has been linked to autoimmune thyroid disorders, especially Graves’ disease, Dr. Williamson said. It’s estimated to affect 17%-41% of patients (Front Endocrinol [Lausanne]. 2017;8:254).
Potentially life-threatening idiopathic thrombocytopenic purpura occurs in 2% of patients on Lemtrada, he said, and anti-GMB nephropathy/Goodpasture’s syndrome has been reported in 0.1%.
Dr. Williamson also noted case reports of autoimmune hemolytic anemia and hepatitis. Earlier this year, three reports in Neurology noted acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients (Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422, doi: 10.1212/WNL.0000000000005420, doi: 10.1212/WNL.0000000000005417).
Dr. Williamson disclosed past consulting for Bayer, Biogen, Celgene, Genentech, EMD Serono, Teva, and Novartis, and current research support from Actelion and Alexion.
NASHVILLE, TENN. – With much unknown about the risks of cancer and vaccination associated with immunosuppressants used in multiple sclerosis treatment, a neurologist advised colleagues to be aware of the potential dangers and take appropriate precautions.
For example, Eric Williamson, MD, of the University of Pennsylvania and Philadelphia Veterans Administration Hospital, said he goes a step further than recommending that adult female patients with MS who take ocrelizumab (Ocrevus) get regular mammograms. Per policy, he also double-checks to make sure that patients actually get screened.
“I know two women who were diagnosed with breast cancer before they began on their treatment because we asked about mammograms,” said Dr. Williamson, who spoke in a presentation about the risks of immunosuppressants in MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.
In regard to cancer as a whole, he said, “it’s unclear if there is any true increased risk in MS patients.” But this doesn’t mean there is no danger, he said, since research into immunosuppressants in other contexts show that they can boost the risk of cancer by three times to as much as several hundred times.
In transplant patients, he said, immunosuppressants are linked to higher rates of lymphoproliferative tumors (such as those linked to Epstein-Barr virus), Kaposi sarcoma, and cutaneous, renal, hepatobiliary, and anogenital tumors.
Research is also hazy in regard to specific immunosuppressants used to treat MS. Two reports published about a decade ago raised the possibility that natalizumab (Tysabri) may have sparked a slightly higher risk cancer in patients taking the drug for Crohn’s disease and MS, respectively; the latter report hinted at a higher risk of melanoma specifically. However, Dr. Williamson said postmarketing surveillance has not detected any further sign of trouble (N Engl J Med. 2006;354:899‐910; N Engl J Med. 2008;358;647‐8).
Another drug, ocrelizumab (Ocrevus), has sparked questions about a possible breast cancer risk. As Genentech, its manufacturer, notes: “breast cancer occurred in 6 of 781 females treated with Ocrevus and none of 668 females treated with Rebif [interferon beta-1a] or placebo.”
However, a researcher reported ocrelizumab open-label extension study data at the 2017 CMSC annual meeting and said, “incidence rates of malignancies and breast cancer observed with ocrelizumab treatment in MS remain within the range of epidemiologic background data.”
For now, Dr. Williamson, said, it may take decades to understand if there’s actually an increased breast cancer risk with ocrelizumab.
Skin cancer is a concern for fingolimod (Gilenya), Dr. Williamson said, specifically basal cell carcinoma and melanoma. It’s debatable whether patients should be required to see a dermatologist or make annual visits, he said. Per policy, his VA employer requires these patients to visit a dermatologist.
Whatever the case, it’s important to keep in mind that skin cancer screenings are advisable in general, he said.
Guidance on vaccinations
On the vaccination front, Dr. Williamson said vaccines are a good idea for MS patients – as long as they’re “relatively safe” – because some infectious diseases appear to be more severe in this population.
Flu is a special danger, Dr. Williamson said. He recommends the flu vaccine to patients “because people with MS are at higher risk of influenza-related complications or hospitalizations.”
With guidance from a report led by Dr. Williamson, the National Multiple Sclerosis Society offers recommendations about whether patients with MS should use various vaccines (Curr Neurol Neurosci Rep. 2016;16:36).
Dr. Williamson cautioned that patients with MS who take dimethyl fumarate (Tecfidera), ocrelizumab (Ocrevus), and fingolimod (Gilenya) should not use live vaccines. The drugs can pose issues in regard to other vaccines, too, he said (Plos ONE 2013; 8:e78532; Neurol Res 2012;34:730-3; Neurology. 2013;81:552-8).
Autoimmune risk with alemtuzumab
Alemtuzumab (Lemtrada) has been linked to autoimmune thyroid disorders, especially Graves’ disease, Dr. Williamson said. It’s estimated to affect 17%-41% of patients (Front Endocrinol [Lausanne]. 2017;8:254).
Potentially life-threatening idiopathic thrombocytopenic purpura occurs in 2% of patients on Lemtrada, he said, and anti-GMB nephropathy/Goodpasture’s syndrome has been reported in 0.1%.
Dr. Williamson also noted case reports of autoimmune hemolytic anemia and hepatitis. Earlier this year, three reports in Neurology noted acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients (Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422, doi: 10.1212/WNL.0000000000005420, doi: 10.1212/WNL.0000000000005417).
Dr. Williamson disclosed past consulting for Bayer, Biogen, Celgene, Genentech, EMD Serono, Teva, and Novartis, and current research support from Actelion and Alexion.
REPORTING FROM THE CMSC ANNUAL MEETING
Global MS trends: A chaotic picture with risk as the central theme
NASHVILLE, Tenn. – Recent epidemiologic studies of multiple sclerosis from around the globe paint a confusing picture, with incidence up in some countries and down in others, latitudinal associations strong in some regions and waning in others, and an overall lack of well-managed databases to bring order to these findings.
Alberto Ascherio, MD, who moderated a global epidemiology session during the annual meeting of the Consortium of Multiple Sclerosis Centers, said it’s tough to draw firm conclusions from the vastly varied studies assessing epidemiologic patterns of MS around the world. Most researchers are trying to extrapolate population data from smaller groups – a process always fraught with the potential for misinterpretation.
Global data, however, converge on some of the most well-established risk factors for the disease, he said. “There seems to be no doubt that vitamin D deficiency, teenager obesity, Epstein-Barr virus infection, and smoking remain strong risk factors for MS in every database in every country that has examined this,” said Dr. Ascherio, a professor of epidemiology and nutrition at Harvard University, Boston.
He sat down for a video interview to pick apart some of the findings from studies in Australia, New Zealand, Western Europe, Canada, and the United States.
Dr. Ascherio had no financial disclosures.
NASHVILLE, Tenn. – Recent epidemiologic studies of multiple sclerosis from around the globe paint a confusing picture, with incidence up in some countries and down in others, latitudinal associations strong in some regions and waning in others, and an overall lack of well-managed databases to bring order to these findings.
Alberto Ascherio, MD, who moderated a global epidemiology session during the annual meeting of the Consortium of Multiple Sclerosis Centers, said it’s tough to draw firm conclusions from the vastly varied studies assessing epidemiologic patterns of MS around the world. Most researchers are trying to extrapolate population data from smaller groups – a process always fraught with the potential for misinterpretation.
Global data, however, converge on some of the most well-established risk factors for the disease, he said. “There seems to be no doubt that vitamin D deficiency, teenager obesity, Epstein-Barr virus infection, and smoking remain strong risk factors for MS in every database in every country that has examined this,” said Dr. Ascherio, a professor of epidemiology and nutrition at Harvard University, Boston.
He sat down for a video interview to pick apart some of the findings from studies in Australia, New Zealand, Western Europe, Canada, and the United States.
Dr. Ascherio had no financial disclosures.
NASHVILLE, Tenn. – Recent epidemiologic studies of multiple sclerosis from around the globe paint a confusing picture, with incidence up in some countries and down in others, latitudinal associations strong in some regions and waning in others, and an overall lack of well-managed databases to bring order to these findings.
Alberto Ascherio, MD, who moderated a global epidemiology session during the annual meeting of the Consortium of Multiple Sclerosis Centers, said it’s tough to draw firm conclusions from the vastly varied studies assessing epidemiologic patterns of MS around the world. Most researchers are trying to extrapolate population data from smaller groups – a process always fraught with the potential for misinterpretation.
Global data, however, converge on some of the most well-established risk factors for the disease, he said. “There seems to be no doubt that vitamin D deficiency, teenager obesity, Epstein-Barr virus infection, and smoking remain strong risk factors for MS in every database in every country that has examined this,” said Dr. Ascherio, a professor of epidemiology and nutrition at Harvard University, Boston.
He sat down for a video interview to pick apart some of the findings from studies in Australia, New Zealand, Western Europe, Canada, and the United States.
Dr. Ascherio had no financial disclosures.
REPORTING FROM THE CMSC ANNUAL MEETING
Focus on preventing comorbidities in MS, physician urges
NASHVILLE, TENN. – Some patients use multiple sclerosis as an excuse to make poor health choices, but Allen C. Bowling, MD, PhD, of the Colorado Neurological Institute has seen another kind of story unfold. Fifteen to 20 years ago, Dr. Bowling said, he treated patients who took the development of MS in their 20s as a sign they needed to take better care of themselves. “They said MS was the best thing that happened to them ‘because it motivated me to make these healthy lifestyle changes I wouldn’t have made otherwise.’ ”
These patients have maintained their lifestyle changes, he said, lowering their risk of comorbidities and – perhaps – changing the course of their MS for the better.
“It’s all one machine, and sometimes we lose sight of that in our sub-sub-specialized world of treating MS ... You’re caring for a whole person. If you start thinking about that, it does make you think differently about how you treat the person, how you try to prevent disease in terms of certain pathways,” Dr. Bowling said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers, where he spoke to colleagues about the importance of helping patients to adopt lifestyle changes.
According to Dr. Bowling, there’s evidence linking lifestyle-related comorbidities, poorer food quality, and tobacco use to higher levels of overall MS risk, relapses, disability, and symptoms.
Researchers have also linked other life factors to higher MS risks: obesity (linked to overall MS risk, disability, symptoms); lack of physical activity (linked to relapses, disability, symptoms); emotional factors (relapses, symptoms); and alcohol overuse (linked to overall risk, disability, symptoms).
“Data is mild to moderate to strong in all those areas for lifestyle approaches like diet, physical activity, emotional health, alcohol in moderation or less, and no tobacco smoking,” Dr. Bowling said.
He said he believes physical activity leads to “much higher and earlier success than diet” in MS patients, although there’s no confirmed “best exercise.”
As for nutrition, he said vitamins D and B12 are possibly beneficial. But he cautioned against the potential for harm from supplements and added that there’s no proven best diet for MS.
As for finding time to address these issues in clinic, Dr. Bowling recommended mentioning various lifestyle issues over multiple office visits.
“Some of the effort should be switched to the primary care doctor,” he said, “but you can use a strong collection of words to convey to the person with MS that this is serious: ‘It’s not MS, but it’s a serious issue, and you must see your primary care doctor.’ ”
He believes that this approach can have a significant impact, “especially for those aged 20-40, because the doctor they pay the most attention to may be their MS clinician.”
Dr. Bowling said that he receives royalties from a book he authored, “Optimal Health With Multiple Sclerosis.”
NASHVILLE, TENN. – Some patients use multiple sclerosis as an excuse to make poor health choices, but Allen C. Bowling, MD, PhD, of the Colorado Neurological Institute has seen another kind of story unfold. Fifteen to 20 years ago, Dr. Bowling said, he treated patients who took the development of MS in their 20s as a sign they needed to take better care of themselves. “They said MS was the best thing that happened to them ‘because it motivated me to make these healthy lifestyle changes I wouldn’t have made otherwise.’ ”
These patients have maintained their lifestyle changes, he said, lowering their risk of comorbidities and – perhaps – changing the course of their MS for the better.
“It’s all one machine, and sometimes we lose sight of that in our sub-sub-specialized world of treating MS ... You’re caring for a whole person. If you start thinking about that, it does make you think differently about how you treat the person, how you try to prevent disease in terms of certain pathways,” Dr. Bowling said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers, where he spoke to colleagues about the importance of helping patients to adopt lifestyle changes.
According to Dr. Bowling, there’s evidence linking lifestyle-related comorbidities, poorer food quality, and tobacco use to higher levels of overall MS risk, relapses, disability, and symptoms.
Researchers have also linked other life factors to higher MS risks: obesity (linked to overall MS risk, disability, symptoms); lack of physical activity (linked to relapses, disability, symptoms); emotional factors (relapses, symptoms); and alcohol overuse (linked to overall risk, disability, symptoms).
“Data is mild to moderate to strong in all those areas for lifestyle approaches like diet, physical activity, emotional health, alcohol in moderation or less, and no tobacco smoking,” Dr. Bowling said.
He said he believes physical activity leads to “much higher and earlier success than diet” in MS patients, although there’s no confirmed “best exercise.”
As for nutrition, he said vitamins D and B12 are possibly beneficial. But he cautioned against the potential for harm from supplements and added that there’s no proven best diet for MS.
As for finding time to address these issues in clinic, Dr. Bowling recommended mentioning various lifestyle issues over multiple office visits.
“Some of the effort should be switched to the primary care doctor,” he said, “but you can use a strong collection of words to convey to the person with MS that this is serious: ‘It’s not MS, but it’s a serious issue, and you must see your primary care doctor.’ ”
He believes that this approach can have a significant impact, “especially for those aged 20-40, because the doctor they pay the most attention to may be their MS clinician.”
Dr. Bowling said that he receives royalties from a book he authored, “Optimal Health With Multiple Sclerosis.”
NASHVILLE, TENN. – Some patients use multiple sclerosis as an excuse to make poor health choices, but Allen C. Bowling, MD, PhD, of the Colorado Neurological Institute has seen another kind of story unfold. Fifteen to 20 years ago, Dr. Bowling said, he treated patients who took the development of MS in their 20s as a sign they needed to take better care of themselves. “They said MS was the best thing that happened to them ‘because it motivated me to make these healthy lifestyle changes I wouldn’t have made otherwise.’ ”
These patients have maintained their lifestyle changes, he said, lowering their risk of comorbidities and – perhaps – changing the course of their MS for the better.
“It’s all one machine, and sometimes we lose sight of that in our sub-sub-specialized world of treating MS ... You’re caring for a whole person. If you start thinking about that, it does make you think differently about how you treat the person, how you try to prevent disease in terms of certain pathways,” Dr. Bowling said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers, where he spoke to colleagues about the importance of helping patients to adopt lifestyle changes.
According to Dr. Bowling, there’s evidence linking lifestyle-related comorbidities, poorer food quality, and tobacco use to higher levels of overall MS risk, relapses, disability, and symptoms.
Researchers have also linked other life factors to higher MS risks: obesity (linked to overall MS risk, disability, symptoms); lack of physical activity (linked to relapses, disability, symptoms); emotional factors (relapses, symptoms); and alcohol overuse (linked to overall risk, disability, symptoms).
“Data is mild to moderate to strong in all those areas for lifestyle approaches like diet, physical activity, emotional health, alcohol in moderation or less, and no tobacco smoking,” Dr. Bowling said.
He said he believes physical activity leads to “much higher and earlier success than diet” in MS patients, although there’s no confirmed “best exercise.”
As for nutrition, he said vitamins D and B12 are possibly beneficial. But he cautioned against the potential for harm from supplements and added that there’s no proven best diet for MS.
As for finding time to address these issues in clinic, Dr. Bowling recommended mentioning various lifestyle issues over multiple office visits.
“Some of the effort should be switched to the primary care doctor,” he said, “but you can use a strong collection of words to convey to the person with MS that this is serious: ‘It’s not MS, but it’s a serious issue, and you must see your primary care doctor.’ ”
He believes that this approach can have a significant impact, “especially for those aged 20-40, because the doctor they pay the most attention to may be their MS clinician.”
Dr. Bowling said that he receives royalties from a book he authored, “Optimal Health With Multiple Sclerosis.”
REPORTING FROM THE CMSC ANNUAL MEETING
Pregnancy may be ideal time to consider switching MS drugs
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NASHVILLE, TENN – Women with multiple sclerosis who fare poorly on specific medications before pregnancy don’t tend to do any better afterward, a new study finds. This suggests that pregnancy – a period when many women with MS stop taking their medication – should trigger discussions about switching from drugs that aren’t doing the job, the study’s lead author said.
“It’s a good time to consider the therapy that the individual is on, whether it’s one that’s effective for them, and whether it’s one they should return to when they start up therapy post-partum. It’s likely it will affect them the same way” after pregnancy as before, Caila Vaughn, MPH, PhD, of the University of Buffalo, said in an interview at the 2018 annual meeting of the Consortium of Multiple Sclerosis Clinics.
From 2012-2017, the study authors sent surveys to 1,651 women in the New York State Multiple Sclerosis Consortium as part of an effort to understand how pregnancy affects women with MS, especially when relapses return in the post-partum period.
Of the 1,651 women, 635 (38% of the total) agreed to answer questions about their reproductive history.
Pregnancy data was available for 627 patients of whom 490 (78%) had been pregnant. Of those, 109 said they became pregnant after their MS diagnosis.
Fifty-three (49%) reported relapses in the 2 years prior to pregnancy and 46% reported them in the 2 subsequent years. Just 12% reported relapses during pregnancy, and 16% said they took disease-modifying drugs during pregnancy (60% had taken them before pregnancy).
Why does MS become less severe during pregnancy? “We believe the dormancy of the disease is related to an immune system that is naturally decreased and depressed during pregnancy,” Dr. Vaughn said. Afterward, she said, “the relapses are related to the recovery of the immune system post-partum.”
The researchers didn’t find any links between the use of disease-modifying drugs and relapses before, during, or after pregnancy.
Those who had relapses prior to pregnancy were more likely (P = 0.011) to have them afterward too. But researchers didn’t find a statistically significant link between relapses that occurred during and after pregnancy.
More than three-quarters of those who took disease-modifying drugs before pregnancy returned to using them afterward, in most cases within 3 months.
The study findings suggest that pregnancy is a helpful decision point when patients should take a closer look at the effects of their medications, Dr. Vaughn said. “In conjunction with a physician, they should decide if it’s a good one they should return to.”
Reflecting the findings of other research that suggests pregnancy is safe in women with MS, the study shows no sign that pregnancy – either before or after diagnosis of MS – boosts the risk that MS will get worse.
As for the possible effects of disease-modifying drugs on new mothers who breast-feed, the researchers found no evidence of adverse outcomes in 5 patients who took the medications while breast-feeding.
The study was funded by Teva. Dr. Vaughn reported no relevant disclosures. Several other study authors report various disclosures, including relationships with Teva.
SOURCE: Vaughn C. et al. Abstract FC04, 2018 annual meeting, Consortium of Multiple Sclerosis Centers.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NASHVILLE, TENN – Women with multiple sclerosis who fare poorly on specific medications before pregnancy don’t tend to do any better afterward, a new study finds. This suggests that pregnancy – a period when many women with MS stop taking their medication – should trigger discussions about switching from drugs that aren’t doing the job, the study’s lead author said.
“It’s a good time to consider the therapy that the individual is on, whether it’s one that’s effective for them, and whether it’s one they should return to when they start up therapy post-partum. It’s likely it will affect them the same way” after pregnancy as before, Caila Vaughn, MPH, PhD, of the University of Buffalo, said in an interview at the 2018 annual meeting of the Consortium of Multiple Sclerosis Clinics.
From 2012-2017, the study authors sent surveys to 1,651 women in the New York State Multiple Sclerosis Consortium as part of an effort to understand how pregnancy affects women with MS, especially when relapses return in the post-partum period.
Of the 1,651 women, 635 (38% of the total) agreed to answer questions about their reproductive history.
Pregnancy data was available for 627 patients of whom 490 (78%) had been pregnant. Of those, 109 said they became pregnant after their MS diagnosis.
Fifty-three (49%) reported relapses in the 2 years prior to pregnancy and 46% reported them in the 2 subsequent years. Just 12% reported relapses during pregnancy, and 16% said they took disease-modifying drugs during pregnancy (60% had taken them before pregnancy).
Why does MS become less severe during pregnancy? “We believe the dormancy of the disease is related to an immune system that is naturally decreased and depressed during pregnancy,” Dr. Vaughn said. Afterward, she said, “the relapses are related to the recovery of the immune system post-partum.”
The researchers didn’t find any links between the use of disease-modifying drugs and relapses before, during, or after pregnancy.
Those who had relapses prior to pregnancy were more likely (P = 0.011) to have them afterward too. But researchers didn’t find a statistically significant link between relapses that occurred during and after pregnancy.
More than three-quarters of those who took disease-modifying drugs before pregnancy returned to using them afterward, in most cases within 3 months.
The study findings suggest that pregnancy is a helpful decision point when patients should take a closer look at the effects of their medications, Dr. Vaughn said. “In conjunction with a physician, they should decide if it’s a good one they should return to.”
Reflecting the findings of other research that suggests pregnancy is safe in women with MS, the study shows no sign that pregnancy – either before or after diagnosis of MS – boosts the risk that MS will get worse.
As for the possible effects of disease-modifying drugs on new mothers who breast-feed, the researchers found no evidence of adverse outcomes in 5 patients who took the medications while breast-feeding.
The study was funded by Teva. Dr. Vaughn reported no relevant disclosures. Several other study authors report various disclosures, including relationships with Teva.
SOURCE: Vaughn C. et al. Abstract FC04, 2018 annual meeting, Consortium of Multiple Sclerosis Centers.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NASHVILLE, TENN – Women with multiple sclerosis who fare poorly on specific medications before pregnancy don’t tend to do any better afterward, a new study finds. This suggests that pregnancy – a period when many women with MS stop taking their medication – should trigger discussions about switching from drugs that aren’t doing the job, the study’s lead author said.
“It’s a good time to consider the therapy that the individual is on, whether it’s one that’s effective for them, and whether it’s one they should return to when they start up therapy post-partum. It’s likely it will affect them the same way” after pregnancy as before, Caila Vaughn, MPH, PhD, of the University of Buffalo, said in an interview at the 2018 annual meeting of the Consortium of Multiple Sclerosis Clinics.
From 2012-2017, the study authors sent surveys to 1,651 women in the New York State Multiple Sclerosis Consortium as part of an effort to understand how pregnancy affects women with MS, especially when relapses return in the post-partum period.
Of the 1,651 women, 635 (38% of the total) agreed to answer questions about their reproductive history.
Pregnancy data was available for 627 patients of whom 490 (78%) had been pregnant. Of those, 109 said they became pregnant after their MS diagnosis.
Fifty-three (49%) reported relapses in the 2 years prior to pregnancy and 46% reported them in the 2 subsequent years. Just 12% reported relapses during pregnancy, and 16% said they took disease-modifying drugs during pregnancy (60% had taken them before pregnancy).
Why does MS become less severe during pregnancy? “We believe the dormancy of the disease is related to an immune system that is naturally decreased and depressed during pregnancy,” Dr. Vaughn said. Afterward, she said, “the relapses are related to the recovery of the immune system post-partum.”
The researchers didn’t find any links between the use of disease-modifying drugs and relapses before, during, or after pregnancy.
Those who had relapses prior to pregnancy were more likely (P = 0.011) to have them afterward too. But researchers didn’t find a statistically significant link between relapses that occurred during and after pregnancy.
More than three-quarters of those who took disease-modifying drugs before pregnancy returned to using them afterward, in most cases within 3 months.
The study findings suggest that pregnancy is a helpful decision point when patients should take a closer look at the effects of their medications, Dr. Vaughn said. “In conjunction with a physician, they should decide if it’s a good one they should return to.”
Reflecting the findings of other research that suggests pregnancy is safe in women with MS, the study shows no sign that pregnancy – either before or after diagnosis of MS – boosts the risk that MS will get worse.
As for the possible effects of disease-modifying drugs on new mothers who breast-feed, the researchers found no evidence of adverse outcomes in 5 patients who took the medications while breast-feeding.
The study was funded by Teva. Dr. Vaughn reported no relevant disclosures. Several other study authors report various disclosures, including relationships with Teva.
SOURCE: Vaughn C. et al. Abstract FC04, 2018 annual meeting, Consortium of Multiple Sclerosis Centers.
REPORTING FROM THE CMSC ANNUAL MEETING
Key clinical point: Multiple sclerosis relapse rates are similar before and after pregnancy, suggesting it may be a good time to consider switching medications if feasible.
Major finding: 49% of women who were pregnant after MS diagnosis reported relapses in the 2 years prior to pregnancy and 46% reported them in the 2 subsequent years. Those who had relapses prior to pregnancy were more likely to have them afterward, too.
Study details: Survey of 109 women who became pregnant after MS diagnosis.
Disclosures: Teva funded the study. Several study authors report various disclosures, including relationships with Teva.
Source: Vaughn C. et al. Abstract FC04, 2018 annual meeting, Consortium of Multiple Sclerosis Centers.
MS clinic thrives by making regular care a ‘loss leader’
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NASHVILLE, TENN. – Care for MS patients is expensive, and even non-profit treatment centers can’t survive on reimbursements alone. The solution, according to Terry Smith, CEO of the Multiple Sclerosis Center of Atlanta, is to transform regular care into a “loss leader” and embrace other revenue sources.
“The reimbursements for that 20- minute or 30-minute follow-up just really don’t cover all the resources necessary for comprehensive care,” Mr. Smith said in a video interview at the 2018 annual meeting of the Consortium of Multiple Sclerosis Clinics.
Mr. Smith said his involvement in the MS community was sparked about 2 decades ago when his wife developed the condition. “I have seen what the center gets reimbursed for her office visit, and then what her neurologist gets reimbursed.”
The reimbursement for an MS patient’s follow-up, 25-minute appointment with a physician is $104.25, according to Mr. Smith. Yet these MS visits are “the cornerstone of treatment ... set the tone for how successful the care is.”
To make make up for losses, the Atlanta center has begun offering its own ancillary services. “Our doctors are at the forefront of telling patients we have a group of neurologists that handle both emergent as well as non-emergent neurology,” he said. “That offers a revenue stream beyond the patient encounter.”
Other sources include imaging and an infusion clinic managed for a local hospital through a professional service agreement. The Atlanta center also has created its own specialty pharmacy focused on MS. “We buy disease-modifying drugs, develop personal contact with patients on a regular basis, then develop an ongoing compliance-monitoring program,” he said.
Mr. Smith discloses a consulting fee from Novartis.
Watch the interview to learn more about the center’s efforts.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NASHVILLE, TENN. – Care for MS patients is expensive, and even non-profit treatment centers can’t survive on reimbursements alone. The solution, according to Terry Smith, CEO of the Multiple Sclerosis Center of Atlanta, is to transform regular care into a “loss leader” and embrace other revenue sources.
“The reimbursements for that 20- minute or 30-minute follow-up just really don’t cover all the resources necessary for comprehensive care,” Mr. Smith said in a video interview at the 2018 annual meeting of the Consortium of Multiple Sclerosis Clinics.
Mr. Smith said his involvement in the MS community was sparked about 2 decades ago when his wife developed the condition. “I have seen what the center gets reimbursed for her office visit, and then what her neurologist gets reimbursed.”
The reimbursement for an MS patient’s follow-up, 25-minute appointment with a physician is $104.25, according to Mr. Smith. Yet these MS visits are “the cornerstone of treatment ... set the tone for how successful the care is.”
To make make up for losses, the Atlanta center has begun offering its own ancillary services. “Our doctors are at the forefront of telling patients we have a group of neurologists that handle both emergent as well as non-emergent neurology,” he said. “That offers a revenue stream beyond the patient encounter.”
Other sources include imaging and an infusion clinic managed for a local hospital through a professional service agreement. The Atlanta center also has created its own specialty pharmacy focused on MS. “We buy disease-modifying drugs, develop personal contact with patients on a regular basis, then develop an ongoing compliance-monitoring program,” he said.
Mr. Smith discloses a consulting fee from Novartis.
Watch the interview to learn more about the center’s efforts.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NASHVILLE, TENN. – Care for MS patients is expensive, and even non-profit treatment centers can’t survive on reimbursements alone. The solution, according to Terry Smith, CEO of the Multiple Sclerosis Center of Atlanta, is to transform regular care into a “loss leader” and embrace other revenue sources.
“The reimbursements for that 20- minute or 30-minute follow-up just really don’t cover all the resources necessary for comprehensive care,” Mr. Smith said in a video interview at the 2018 annual meeting of the Consortium of Multiple Sclerosis Clinics.
Mr. Smith said his involvement in the MS community was sparked about 2 decades ago when his wife developed the condition. “I have seen what the center gets reimbursed for her office visit, and then what her neurologist gets reimbursed.”
The reimbursement for an MS patient’s follow-up, 25-minute appointment with a physician is $104.25, according to Mr. Smith. Yet these MS visits are “the cornerstone of treatment ... set the tone for how successful the care is.”
To make make up for losses, the Atlanta center has begun offering its own ancillary services. “Our doctors are at the forefront of telling patients we have a group of neurologists that handle both emergent as well as non-emergent neurology,” he said. “That offers a revenue stream beyond the patient encounter.”
Other sources include imaging and an infusion clinic managed for a local hospital through a professional service agreement. The Atlanta center also has created its own specialty pharmacy focused on MS. “We buy disease-modifying drugs, develop personal contact with patients on a regular basis, then develop an ongoing compliance-monitoring program,” he said.
Mr. Smith discloses a consulting fee from Novartis.
Watch the interview to learn more about the center’s efforts.
REPORTING FROM THE CMSC ANNUAL MEETING
New guidelines for gadolinium-based contrast agents take conservative stance
NASHVILLE, Tenn. – Gadolinium-based contrast agents (GBCAs) are necessary for the accurate initial diagnosis of patients experiencing a first clinical attack of symptoms consistent with multiple sclerosis and for following patients with highly active disease or sudden, unexpected declines.
But according to new guidelines issued by the Consortium of Multiple Sclerosis Centers, GBCAs are optional – although helpful – in many other clinical scenarios, especially when noncontrast MRI can provide answers.
“The key is that there is an optional role for gadolinium,” David Li, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. Although a GBCA is still “essential” for some clinical scenarios in clinically isolated syndrome and MS, the
“But I would like to remind you that if you need to know about ongoing, current activity,” in settings of acute change, then gadolinium is still necessary, Dr. Li of the University of British Columbia, Vancouver, said in a video interview.
The guideline is an update of CMSC’s 2015 document, which endorsed a more liberal use of GBCAs. This more conservative stance reflects new research on the agents and an update in 2017 from the Food and Drug Administration that required a class-wide warning about gadolinium retention.
The agency began investigating gadolinium in 2015. In May 2017, it issued a statement confirming that gadolinium accumulates in neural tissue and can be retained for an extended period. However, in reviewing the evidence, FDA found no concerning safety signals. Despite the presumed lack of toxicity, the agency issued the warning and recommended limiting the contrast agent’s use – a move reflected in CMSC’s new MRI protocol guidelines.
“While there is no known CNS toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS,” the document notes.
Dr. Li concurred.
“It remains indispensable in patients presenting with their first clinical attack (CIS) as [its] use allows for an earlier diagnosis by demonstrating lesion dissemination in time in addition to lesion dissemination in space, the hallmarks for the diagnosis of MS. Early diagnosis leads to early treatment, which may help in preventing disease progression and improve long-term prognosis.”
Dr. Li has received multiple drug company grants and acted as a consultant to multiple pharmaceutical companies, but had no disclosures relevant to gadolinium.
NASHVILLE, Tenn. – Gadolinium-based contrast agents (GBCAs) are necessary for the accurate initial diagnosis of patients experiencing a first clinical attack of symptoms consistent with multiple sclerosis and for following patients with highly active disease or sudden, unexpected declines.
But according to new guidelines issued by the Consortium of Multiple Sclerosis Centers, GBCAs are optional – although helpful – in many other clinical scenarios, especially when noncontrast MRI can provide answers.
“The key is that there is an optional role for gadolinium,” David Li, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. Although a GBCA is still “essential” for some clinical scenarios in clinically isolated syndrome and MS, the
“But I would like to remind you that if you need to know about ongoing, current activity,” in settings of acute change, then gadolinium is still necessary, Dr. Li of the University of British Columbia, Vancouver, said in a video interview.
The guideline is an update of CMSC’s 2015 document, which endorsed a more liberal use of GBCAs. This more conservative stance reflects new research on the agents and an update in 2017 from the Food and Drug Administration that required a class-wide warning about gadolinium retention.
The agency began investigating gadolinium in 2015. In May 2017, it issued a statement confirming that gadolinium accumulates in neural tissue and can be retained for an extended period. However, in reviewing the evidence, FDA found no concerning safety signals. Despite the presumed lack of toxicity, the agency issued the warning and recommended limiting the contrast agent’s use – a move reflected in CMSC’s new MRI protocol guidelines.
“While there is no known CNS toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS,” the document notes.
Dr. Li concurred.
“It remains indispensable in patients presenting with their first clinical attack (CIS) as [its] use allows for an earlier diagnosis by demonstrating lesion dissemination in time in addition to lesion dissemination in space, the hallmarks for the diagnosis of MS. Early diagnosis leads to early treatment, which may help in preventing disease progression and improve long-term prognosis.”
Dr. Li has received multiple drug company grants and acted as a consultant to multiple pharmaceutical companies, but had no disclosures relevant to gadolinium.
NASHVILLE, Tenn. – Gadolinium-based contrast agents (GBCAs) are necessary for the accurate initial diagnosis of patients experiencing a first clinical attack of symptoms consistent with multiple sclerosis and for following patients with highly active disease or sudden, unexpected declines.
But according to new guidelines issued by the Consortium of Multiple Sclerosis Centers, GBCAs are optional – although helpful – in many other clinical scenarios, especially when noncontrast MRI can provide answers.
“The key is that there is an optional role for gadolinium,” David Li, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. Although a GBCA is still “essential” for some clinical scenarios in clinically isolated syndrome and MS, the
“But I would like to remind you that if you need to know about ongoing, current activity,” in settings of acute change, then gadolinium is still necessary, Dr. Li of the University of British Columbia, Vancouver, said in a video interview.
The guideline is an update of CMSC’s 2015 document, which endorsed a more liberal use of GBCAs. This more conservative stance reflects new research on the agents and an update in 2017 from the Food and Drug Administration that required a class-wide warning about gadolinium retention.
The agency began investigating gadolinium in 2015. In May 2017, it issued a statement confirming that gadolinium accumulates in neural tissue and can be retained for an extended period. However, in reviewing the evidence, FDA found no concerning safety signals. Despite the presumed lack of toxicity, the agency issued the warning and recommended limiting the contrast agent’s use – a move reflected in CMSC’s new MRI protocol guidelines.
“While there is no known CNS toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS,” the document notes.
Dr. Li concurred.
“It remains indispensable in patients presenting with their first clinical attack (CIS) as [its] use allows for an earlier diagnosis by demonstrating lesion dissemination in time in addition to lesion dissemination in space, the hallmarks for the diagnosis of MS. Early diagnosis leads to early treatment, which may help in preventing disease progression and improve long-term prognosis.”
Dr. Li has received multiple drug company grants and acted as a consultant to multiple pharmaceutical companies, but had no disclosures relevant to gadolinium.
REPORTING FROM THE CMSC ANNUAL MEETING
VIDEO: PML prevention is possible, even when treating patients with aggressive MS
NASHVILLE, TENN. – Armed with new statistics, neurologist Joseph R. Berger, MD, has a message for colleagues about the widely feared risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis: It’s not as inevitable as you might think.
“You can actually prevent this disease from occurring because we have risk-limiting strategies in many circumstances,” said Dr. Berger of the University of Pennsylvania, Philadelphia, in a presentation on PML at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Unlike other conditions such as HIV, MS itself is not linked to a higher risk of PML, said Dr. Berger, a leading PML researcher. Instead, it’s the medications that spark the condition, he said, with at least three and possibly four drugs posing a risk to patients.
Natalizumab (Tysabri) is especially risky. “We know that the risk with natalizumab is incredibly high in the context of JC [John Cunningham] virus antibody positivity and prolonged therapy,” Dr. Berger said in an interview after his presentation.
Still, “you can safely give natalizumab for a short period of time when treating patients with aggressive MS,” he said. “I will frequently employ that strategy even in the context of JC virus antibody positivity.”
According to Dr. Berger, there’s no risk of PML when natalizumab is used for under 8 months (Mult Scler Relat Disord. 2017 Feb;12:59-63).
However, “if you leave people on the drug indefinitely, there is a substantial risk of developing PML,” he said. “Individuals who have been left on the drug for 2 years, who’ve seen prior immunosuppressant therapy, who are JC virus antibody positive – that group of individuals develops PML at rates of 1 in 50 to 1 in 100.”
These levels are “enormous,” he said, higher even than those in the HIV population before the rise of antiretroviral medications.
Overall, as of Nov. 30, 2017, 177,800 patients have received natalizumab in the postmarketing setting, and 756 cases of PML have been reported as of Dec. 7, 2017. All but three of those cases were in patients with MS, and the overall incidence was 4.19/1,000.
Dr. Berger recommends regular screening MRIs for PML in patients taking natalizumab, and he advised physicians to be on alert for signs of trouble like the appearance of new neurologic symptoms or a new or increasing JC virus antibody index.
Two other MS drugs, fingolimod (Gilenya) and dimethyl fumarate (Tecfidera), fall into the category of low risk, with just 19 and 5 reported cases, respectively, as of February 2018, Dr. Berger said. He added that two of the fingolimod patients had earlier exposure to natalizumab.
With dimethyl fumarate, the risk appears to disappear – although this isn’t confirmed – when JC antibody–positive patients are taken off the drug, and their lymphocyte counts fall below 500 per mcL, Dr. Berger said.
“Unfortunately for fingolimod, we don’t have a defined risk-mitigation strategy,” he said. However, researchers have noticed that the fingolimod cases have occurred more often in older people, possibly because of the aging of the immune system, he said.
Another three MS drugs – alemtuzumab (Lemtrada), ocrelizumab (Ocrevus; with rituximab as proxy), and teriflunomide (Aubagio; with leflunomide as proxy) have unknown risk, according to Dr. Berger. There have been three cases in ocrelizumab (rituximab as proxy) and one in teriflunomide (leflunomide as proxy), but all were carry-overs from natalizumab or fingolimod exposure or occurred after natalizumab exposure.
What can physicians do if a patient develops PML? Stopping the drug and restoring the immune system is crucial, he said.
While there’s evidence that plasma exchange clears natalizumab (Neurology. 2009 Feb 3;72[5]:402-9), “there’s no study that demonstrates it’s in the patient’s best interest,” Dr. Berger said during his presentation. He noted that a retrospective study found no improvement in morbidity or mortality (Neurology. 2017 Mar 21;88[12];1144-52).
Multiple strategies to treat PML – including immunizations and inhibitors of DNA replication – have failed to make an impact so far, Dr. Berger said. According to him, the reasons for the failure of PML treatment are a lack of hard evidence, apart from anecdotal, to support them, based on a history of failed clinical trials.
Dr. Berger disclosed serving as a consultant for numerous pharmaceutical companies.
NASHVILLE, TENN. – Armed with new statistics, neurologist Joseph R. Berger, MD, has a message for colleagues about the widely feared risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis: It’s not as inevitable as you might think.
“You can actually prevent this disease from occurring because we have risk-limiting strategies in many circumstances,” said Dr. Berger of the University of Pennsylvania, Philadelphia, in a presentation on PML at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Unlike other conditions such as HIV, MS itself is not linked to a higher risk of PML, said Dr. Berger, a leading PML researcher. Instead, it’s the medications that spark the condition, he said, with at least three and possibly four drugs posing a risk to patients.
Natalizumab (Tysabri) is especially risky. “We know that the risk with natalizumab is incredibly high in the context of JC [John Cunningham] virus antibody positivity and prolonged therapy,” Dr. Berger said in an interview after his presentation.
Still, “you can safely give natalizumab for a short period of time when treating patients with aggressive MS,” he said. “I will frequently employ that strategy even in the context of JC virus antibody positivity.”
According to Dr. Berger, there’s no risk of PML when natalizumab is used for under 8 months (Mult Scler Relat Disord. 2017 Feb;12:59-63).
However, “if you leave people on the drug indefinitely, there is a substantial risk of developing PML,” he said. “Individuals who have been left on the drug for 2 years, who’ve seen prior immunosuppressant therapy, who are JC virus antibody positive – that group of individuals develops PML at rates of 1 in 50 to 1 in 100.”
These levels are “enormous,” he said, higher even than those in the HIV population before the rise of antiretroviral medications.
Overall, as of Nov. 30, 2017, 177,800 patients have received natalizumab in the postmarketing setting, and 756 cases of PML have been reported as of Dec. 7, 2017. All but three of those cases were in patients with MS, and the overall incidence was 4.19/1,000.
Dr. Berger recommends regular screening MRIs for PML in patients taking natalizumab, and he advised physicians to be on alert for signs of trouble like the appearance of new neurologic symptoms or a new or increasing JC virus antibody index.
Two other MS drugs, fingolimod (Gilenya) and dimethyl fumarate (Tecfidera), fall into the category of low risk, with just 19 and 5 reported cases, respectively, as of February 2018, Dr. Berger said. He added that two of the fingolimod patients had earlier exposure to natalizumab.
With dimethyl fumarate, the risk appears to disappear – although this isn’t confirmed – when JC antibody–positive patients are taken off the drug, and their lymphocyte counts fall below 500 per mcL, Dr. Berger said.
“Unfortunately for fingolimod, we don’t have a defined risk-mitigation strategy,” he said. However, researchers have noticed that the fingolimod cases have occurred more often in older people, possibly because of the aging of the immune system, he said.
Another three MS drugs – alemtuzumab (Lemtrada), ocrelizumab (Ocrevus; with rituximab as proxy), and teriflunomide (Aubagio; with leflunomide as proxy) have unknown risk, according to Dr. Berger. There have been three cases in ocrelizumab (rituximab as proxy) and one in teriflunomide (leflunomide as proxy), but all were carry-overs from natalizumab or fingolimod exposure or occurred after natalizumab exposure.
What can physicians do if a patient develops PML? Stopping the drug and restoring the immune system is crucial, he said.
While there’s evidence that plasma exchange clears natalizumab (Neurology. 2009 Feb 3;72[5]:402-9), “there’s no study that demonstrates it’s in the patient’s best interest,” Dr. Berger said during his presentation. He noted that a retrospective study found no improvement in morbidity or mortality (Neurology. 2017 Mar 21;88[12];1144-52).
Multiple strategies to treat PML – including immunizations and inhibitors of DNA replication – have failed to make an impact so far, Dr. Berger said. According to him, the reasons for the failure of PML treatment are a lack of hard evidence, apart from anecdotal, to support them, based on a history of failed clinical trials.
Dr. Berger disclosed serving as a consultant for numerous pharmaceutical companies.
NASHVILLE, TENN. – Armed with new statistics, neurologist Joseph R. Berger, MD, has a message for colleagues about the widely feared risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis: It’s not as inevitable as you might think.
“You can actually prevent this disease from occurring because we have risk-limiting strategies in many circumstances,” said Dr. Berger of the University of Pennsylvania, Philadelphia, in a presentation on PML at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Unlike other conditions such as HIV, MS itself is not linked to a higher risk of PML, said Dr. Berger, a leading PML researcher. Instead, it’s the medications that spark the condition, he said, with at least three and possibly four drugs posing a risk to patients.
Natalizumab (Tysabri) is especially risky. “We know that the risk with natalizumab is incredibly high in the context of JC [John Cunningham] virus antibody positivity and prolonged therapy,” Dr. Berger said in an interview after his presentation.
Still, “you can safely give natalizumab for a short period of time when treating patients with aggressive MS,” he said. “I will frequently employ that strategy even in the context of JC virus antibody positivity.”
According to Dr. Berger, there’s no risk of PML when natalizumab is used for under 8 months (Mult Scler Relat Disord. 2017 Feb;12:59-63).
However, “if you leave people on the drug indefinitely, there is a substantial risk of developing PML,” he said. “Individuals who have been left on the drug for 2 years, who’ve seen prior immunosuppressant therapy, who are JC virus antibody positive – that group of individuals develops PML at rates of 1 in 50 to 1 in 100.”
These levels are “enormous,” he said, higher even than those in the HIV population before the rise of antiretroviral medications.
Overall, as of Nov. 30, 2017, 177,800 patients have received natalizumab in the postmarketing setting, and 756 cases of PML have been reported as of Dec. 7, 2017. All but three of those cases were in patients with MS, and the overall incidence was 4.19/1,000.
Dr. Berger recommends regular screening MRIs for PML in patients taking natalizumab, and he advised physicians to be on alert for signs of trouble like the appearance of new neurologic symptoms or a new or increasing JC virus antibody index.
Two other MS drugs, fingolimod (Gilenya) and dimethyl fumarate (Tecfidera), fall into the category of low risk, with just 19 and 5 reported cases, respectively, as of February 2018, Dr. Berger said. He added that two of the fingolimod patients had earlier exposure to natalizumab.
With dimethyl fumarate, the risk appears to disappear – although this isn’t confirmed – when JC antibody–positive patients are taken off the drug, and their lymphocyte counts fall below 500 per mcL, Dr. Berger said.
“Unfortunately for fingolimod, we don’t have a defined risk-mitigation strategy,” he said. However, researchers have noticed that the fingolimod cases have occurred more often in older people, possibly because of the aging of the immune system, he said.
Another three MS drugs – alemtuzumab (Lemtrada), ocrelizumab (Ocrevus; with rituximab as proxy), and teriflunomide (Aubagio; with leflunomide as proxy) have unknown risk, according to Dr. Berger. There have been three cases in ocrelizumab (rituximab as proxy) and one in teriflunomide (leflunomide as proxy), but all were carry-overs from natalizumab or fingolimod exposure or occurred after natalizumab exposure.
What can physicians do if a patient develops PML? Stopping the drug and restoring the immune system is crucial, he said.
While there’s evidence that plasma exchange clears natalizumab (Neurology. 2009 Feb 3;72[5]:402-9), “there’s no study that demonstrates it’s in the patient’s best interest,” Dr. Berger said during his presentation. He noted that a retrospective study found no improvement in morbidity or mortality (Neurology. 2017 Mar 21;88[12];1144-52).
Multiple strategies to treat PML – including immunizations and inhibitors of DNA replication – have failed to make an impact so far, Dr. Berger said. According to him, the reasons for the failure of PML treatment are a lack of hard evidence, apart from anecdotal, to support them, based on a history of failed clinical trials.
Dr. Berger disclosed serving as a consultant for numerous pharmaceutical companies.
REPORTING FROM THE CMSC ANNUAL MEETING
Research on exercise in MS needs to build up some muscle
NASHVILLE, TENN. – Physical activity appears to have profound rehabilitative effects – both physical and cognitive – upon patients with multiple sclerosis, but the body of evidence remains largely based on small, sometimes problematic studies, Alan Thompson, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers.
There are compelling animal data that exercise promotes a number of beneficial neuronal changes that improve patient-reported outcomes, said Dr. Thompson, the Garfield Weston Professor of Clinical Neurology and Neurorehabilitation at University College London (England).
“A lot of animal work suggests that exercise can have a major impact on repair and recovery in neurons, synaptic signaling, dendritic branching, long-term potentiation,” and can beneficially affect inflammation and demyelination, he said. Besides the direct effect on nerves, exercise builds up muscle mass, strengthens connective tissue, improves movement, and reduces cardiovascular risk. “Exercise improves inactivity, but also may improve the underlying disease process,” he said. “The effect can be quite profound, and we are building a very good evidence base to support the use of exercise in MS.”
Unfortunately, the existing body of literature remains unimpressive, Dr. Thompson admitted. He compared research in physical activity to that of medicinal therapeutics. Disease-modifying therapeutics research is highly regulated, very well funded, adequately powered and replicated, and – once it shows positive results – receives substantial marketing and sales effort. “As a result, there can be a substantial impact on care.”
Research on rehabilitation and symptom management, with physical activity and other similar interventions, is not well funded, relies on diverse outcome measures, has small cohort numbers, and often is unreplicated. Even positive results “are just left to lie there,” he said. “Thus, it has a modest impact on care. I would like to see equal resources for both research areas.”
The recent surge in stroke rehabilitation is an excellent example of how academic focus can change practice for neurologic illness, he said. A 2017 research letter in Lancet Neurology described the current state of research on exercise in MS (Lancet Neurol. 2017;16[10];848-56). An accompanying editorial compared the MS literature to that in stroke (Lancet Neurol. 2017;16[10]:768-9).
During 1990-2005, there were almost no clinical studies in rehabilitation for stroke, Parkinson’s disease, spinal cord injury, and MS. Around 2005, things began to change in stroke, with close to 60 publications in just 1 year. During 2010-2015, the pace of research accelerated dramatically. Researchers, clinicians, and patients began to see the immediate and long-term benefits of early poststroke rehabilitation. These interventions have now been encoded in practice guidelines and are a core part of clinical care, Dr. Thompson said.
The picture in MS, Parkinson’s, and spinal cord injury remained almost unchanged, although there has been a very slight increase in these studies since 2010.
“We are way behind the stroke research,” Dr. Thompson said. “We need global collaboration to correct this.”
That may be coming. Dr. Thompson described a newly minted, multinational study sponsored by the Canadian Multiple Sclerosis Society. The four-armed “Improving Cognition in People with Progressive MS” study will determine whether cognitive rehabilitation and exercise are effective treatments for cognitive dysfunction in people with progressive MS. It seeks to enroll 360 patients in six countries. They will be randomized to a wait list, exercise plus cognitive rehabilitation, exercise only, or cognitive rehabilitation only.
The primary investigator is Anthony Feinstein, MBBCh, PhD, a psychiatrist at the University of Toronto.
Dr. Thompson had no disclosures relevant to his discussion.
NASHVILLE, TENN. – Physical activity appears to have profound rehabilitative effects – both physical and cognitive – upon patients with multiple sclerosis, but the body of evidence remains largely based on small, sometimes problematic studies, Alan Thompson, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers.
There are compelling animal data that exercise promotes a number of beneficial neuronal changes that improve patient-reported outcomes, said Dr. Thompson, the Garfield Weston Professor of Clinical Neurology and Neurorehabilitation at University College London (England).
“A lot of animal work suggests that exercise can have a major impact on repair and recovery in neurons, synaptic signaling, dendritic branching, long-term potentiation,” and can beneficially affect inflammation and demyelination, he said. Besides the direct effect on nerves, exercise builds up muscle mass, strengthens connective tissue, improves movement, and reduces cardiovascular risk. “Exercise improves inactivity, but also may improve the underlying disease process,” he said. “The effect can be quite profound, and we are building a very good evidence base to support the use of exercise in MS.”
Unfortunately, the existing body of literature remains unimpressive, Dr. Thompson admitted. He compared research in physical activity to that of medicinal therapeutics. Disease-modifying therapeutics research is highly regulated, very well funded, adequately powered and replicated, and – once it shows positive results – receives substantial marketing and sales effort. “As a result, there can be a substantial impact on care.”
Research on rehabilitation and symptom management, with physical activity and other similar interventions, is not well funded, relies on diverse outcome measures, has small cohort numbers, and often is unreplicated. Even positive results “are just left to lie there,” he said. “Thus, it has a modest impact on care. I would like to see equal resources for both research areas.”
The recent surge in stroke rehabilitation is an excellent example of how academic focus can change practice for neurologic illness, he said. A 2017 research letter in Lancet Neurology described the current state of research on exercise in MS (Lancet Neurol. 2017;16[10];848-56). An accompanying editorial compared the MS literature to that in stroke (Lancet Neurol. 2017;16[10]:768-9).
During 1990-2005, there were almost no clinical studies in rehabilitation for stroke, Parkinson’s disease, spinal cord injury, and MS. Around 2005, things began to change in stroke, with close to 60 publications in just 1 year. During 2010-2015, the pace of research accelerated dramatically. Researchers, clinicians, and patients began to see the immediate and long-term benefits of early poststroke rehabilitation. These interventions have now been encoded in practice guidelines and are a core part of clinical care, Dr. Thompson said.
The picture in MS, Parkinson’s, and spinal cord injury remained almost unchanged, although there has been a very slight increase in these studies since 2010.
“We are way behind the stroke research,” Dr. Thompson said. “We need global collaboration to correct this.”
That may be coming. Dr. Thompson described a newly minted, multinational study sponsored by the Canadian Multiple Sclerosis Society. The four-armed “Improving Cognition in People with Progressive MS” study will determine whether cognitive rehabilitation and exercise are effective treatments for cognitive dysfunction in people with progressive MS. It seeks to enroll 360 patients in six countries. They will be randomized to a wait list, exercise plus cognitive rehabilitation, exercise only, or cognitive rehabilitation only.
The primary investigator is Anthony Feinstein, MBBCh, PhD, a psychiatrist at the University of Toronto.
Dr. Thompson had no disclosures relevant to his discussion.
NASHVILLE, TENN. – Physical activity appears to have profound rehabilitative effects – both physical and cognitive – upon patients with multiple sclerosis, but the body of evidence remains largely based on small, sometimes problematic studies, Alan Thompson, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers.
There are compelling animal data that exercise promotes a number of beneficial neuronal changes that improve patient-reported outcomes, said Dr. Thompson, the Garfield Weston Professor of Clinical Neurology and Neurorehabilitation at University College London (England).
“A lot of animal work suggests that exercise can have a major impact on repair and recovery in neurons, synaptic signaling, dendritic branching, long-term potentiation,” and can beneficially affect inflammation and demyelination, he said. Besides the direct effect on nerves, exercise builds up muscle mass, strengthens connective tissue, improves movement, and reduces cardiovascular risk. “Exercise improves inactivity, but also may improve the underlying disease process,” he said. “The effect can be quite profound, and we are building a very good evidence base to support the use of exercise in MS.”
Unfortunately, the existing body of literature remains unimpressive, Dr. Thompson admitted. He compared research in physical activity to that of medicinal therapeutics. Disease-modifying therapeutics research is highly regulated, very well funded, adequately powered and replicated, and – once it shows positive results – receives substantial marketing and sales effort. “As a result, there can be a substantial impact on care.”
Research on rehabilitation and symptom management, with physical activity and other similar interventions, is not well funded, relies on diverse outcome measures, has small cohort numbers, and often is unreplicated. Even positive results “are just left to lie there,” he said. “Thus, it has a modest impact on care. I would like to see equal resources for both research areas.”
The recent surge in stroke rehabilitation is an excellent example of how academic focus can change practice for neurologic illness, he said. A 2017 research letter in Lancet Neurology described the current state of research on exercise in MS (Lancet Neurol. 2017;16[10];848-56). An accompanying editorial compared the MS literature to that in stroke (Lancet Neurol. 2017;16[10]:768-9).
During 1990-2005, there were almost no clinical studies in rehabilitation for stroke, Parkinson’s disease, spinal cord injury, and MS. Around 2005, things began to change in stroke, with close to 60 publications in just 1 year. During 2010-2015, the pace of research accelerated dramatically. Researchers, clinicians, and patients began to see the immediate and long-term benefits of early poststroke rehabilitation. These interventions have now been encoded in practice guidelines and are a core part of clinical care, Dr. Thompson said.
The picture in MS, Parkinson’s, and spinal cord injury remained almost unchanged, although there has been a very slight increase in these studies since 2010.
“We are way behind the stroke research,” Dr. Thompson said. “We need global collaboration to correct this.”
That may be coming. Dr. Thompson described a newly minted, multinational study sponsored by the Canadian Multiple Sclerosis Society. The four-armed “Improving Cognition in People with Progressive MS” study will determine whether cognitive rehabilitation and exercise are effective treatments for cognitive dysfunction in people with progressive MS. It seeks to enroll 360 patients in six countries. They will be randomized to a wait list, exercise plus cognitive rehabilitation, exercise only, or cognitive rehabilitation only.
The primary investigator is Anthony Feinstein, MBBCh, PhD, a psychiatrist at the University of Toronto.
Dr. Thompson had no disclosures relevant to his discussion.
REPORTING FROM THE CMSC ANNUAL MEETING
Pediatric MS gets a win with fingolimod
NASHVILLE, TENN. – Pediatric multiple sclerosis is a confirmed clinical entity, which virtually always presents as relapsing-remitting disease, Brenda Banwell, MD, said at the at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“MS in children is the same disease as MS in adults,” said Dr. Banwell, chief of neurology at Children’s Hospital of Philadelphia and the Grace R. Loeb Endowed Chair in Neurosciences there. And although she is unaware of a single case of childhood MS presenting as primary progressive disease, the impact of relapsing-remitting childhood MS may ultimately be progressive damage.
Pediatric MS is also quite rare, a characteristic that makes therapeutic progress challenging. Recruiting sufficient patients for a definitive phase 3 trial is incredibly difficult, especially when multiple trials are commencing simultaneously, not only in the United States but around the world.
Nevertheless, there has been excellent news, Dr. Banwell said in a video interview. Fingolimod (Gilenya), the immunomodulator approved for adult relapsing-remitting MS, gained a pediatric approval under the breakthrough therapy designation on May 11, 2018, on the basis of the successful phase 3 PARADIGMS study.
Compared with intramuscular interferon beta-1a, fingolimod cut the annualized relapse rate by 82%. It also was associated with a 53% annualized reduction in new or newly enlarged T2 lesions and 66% decrease in gadolinium-enhancing T1 lesions.
This big win is prompting researchers and clinicians to rethink the pediatric MS treatment paradigm, Dr. Banwell said. Traditional thinking falls along a dose-escalation pattern that follows relapses. However, “we may take a cue from our rheumatology colleagues, who have seen the benefit of starting with more aggressive treatment and higher doses, getting disease control, and then slowly tapering off.”
Whether this option could actually modify disease progression, as it seems to do in some other inflammatory disorders, is an intriguing – but unproven – possibility, she said.
Dr. Banwell disclosed that she received financial remuneration as a central MRI reviewer for the Novartis-sponsored PARADIGMS study.
NASHVILLE, TENN. – Pediatric multiple sclerosis is a confirmed clinical entity, which virtually always presents as relapsing-remitting disease, Brenda Banwell, MD, said at the at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“MS in children is the same disease as MS in adults,” said Dr. Banwell, chief of neurology at Children’s Hospital of Philadelphia and the Grace R. Loeb Endowed Chair in Neurosciences there. And although she is unaware of a single case of childhood MS presenting as primary progressive disease, the impact of relapsing-remitting childhood MS may ultimately be progressive damage.
Pediatric MS is also quite rare, a characteristic that makes therapeutic progress challenging. Recruiting sufficient patients for a definitive phase 3 trial is incredibly difficult, especially when multiple trials are commencing simultaneously, not only in the United States but around the world.
Nevertheless, there has been excellent news, Dr. Banwell said in a video interview. Fingolimod (Gilenya), the immunomodulator approved for adult relapsing-remitting MS, gained a pediatric approval under the breakthrough therapy designation on May 11, 2018, on the basis of the successful phase 3 PARADIGMS study.
Compared with intramuscular interferon beta-1a, fingolimod cut the annualized relapse rate by 82%. It also was associated with a 53% annualized reduction in new or newly enlarged T2 lesions and 66% decrease in gadolinium-enhancing T1 lesions.
This big win is prompting researchers and clinicians to rethink the pediatric MS treatment paradigm, Dr. Banwell said. Traditional thinking falls along a dose-escalation pattern that follows relapses. However, “we may take a cue from our rheumatology colleagues, who have seen the benefit of starting with more aggressive treatment and higher doses, getting disease control, and then slowly tapering off.”
Whether this option could actually modify disease progression, as it seems to do in some other inflammatory disorders, is an intriguing – but unproven – possibility, she said.
Dr. Banwell disclosed that she received financial remuneration as a central MRI reviewer for the Novartis-sponsored PARADIGMS study.
NASHVILLE, TENN. – Pediatric multiple sclerosis is a confirmed clinical entity, which virtually always presents as relapsing-remitting disease, Brenda Banwell, MD, said at the at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“MS in children is the same disease as MS in adults,” said Dr. Banwell, chief of neurology at Children’s Hospital of Philadelphia and the Grace R. Loeb Endowed Chair in Neurosciences there. And although she is unaware of a single case of childhood MS presenting as primary progressive disease, the impact of relapsing-remitting childhood MS may ultimately be progressive damage.
Pediatric MS is also quite rare, a characteristic that makes therapeutic progress challenging. Recruiting sufficient patients for a definitive phase 3 trial is incredibly difficult, especially when multiple trials are commencing simultaneously, not only in the United States but around the world.
Nevertheless, there has been excellent news, Dr. Banwell said in a video interview. Fingolimod (Gilenya), the immunomodulator approved for adult relapsing-remitting MS, gained a pediatric approval under the breakthrough therapy designation on May 11, 2018, on the basis of the successful phase 3 PARADIGMS study.
Compared with intramuscular interferon beta-1a, fingolimod cut the annualized relapse rate by 82%. It also was associated with a 53% annualized reduction in new or newly enlarged T2 lesions and 66% decrease in gadolinium-enhancing T1 lesions.
This big win is prompting researchers and clinicians to rethink the pediatric MS treatment paradigm, Dr. Banwell said. Traditional thinking falls along a dose-escalation pattern that follows relapses. However, “we may take a cue from our rheumatology colleagues, who have seen the benefit of starting with more aggressive treatment and higher doses, getting disease control, and then slowly tapering off.”
Whether this option could actually modify disease progression, as it seems to do in some other inflammatory disorders, is an intriguing – but unproven – possibility, she said.
Dr. Banwell disclosed that she received financial remuneration as a central MRI reviewer for the Novartis-sponsored PARADIGMS study.
REPORTING FROM THE CMSC ANNUAL MEETING
