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Ocrelizumab’s Benefits on Confirmed Disability Improvement Persist in Open-Label Extension
This outcome remains more likely in patients who started on ocrelizumab than in those who switched to it from interferon beta.
NASHVILLE—The benefits of ocrelizumab on 24-week confirmed disability improvement, which were demonstrated in two-year, double-blind, controlled trials, were maintained for two years in an open-label extension study in patients with relapsing-remitting multiple sclerosis (MS), according to data described at the 2018 CMSC Annual Meeting.
The 96-week, double-blind, controlled periods of the OPERA I and II trials demonstrated the efficacy and safety of ocrelizumab in relapsing-remitting MS. Upon completion of the controlled treatment periods, all patients were eligible to enter an open-label extension phase during which they would receive ocrelizumab. Robert T. Naismith, MD, Associate Professor of Neurology at Washington University School of Medicine in St. Louis, and colleagues reviewed data from this extension phase to assess the effect of switching to ocrelizumab or maintaining ocrelizumab therapy on the proportion of patients experiencing disability improvement.
Difference Between Groups Endured
During the controlled treatment period, patients received IV ocrelizumab (600 mg) every 24 weeks or subcutaneous interferon beta-1a (44 μg) three times weekly for 96 weeks. At the start of the open-label extension period, patients continued ocrelizumab or were switched from interferon beta-1a to ocrelizumab. Disability improvement compared with baseline was defined as a reduction in Expanded Disability Status Scale (EDSS) score of 1.0 or more points for patients with a baseline EDSS score from 2.0 to 5.5, or a reduction of 0.5 or more points for patients with a baseline EDSS score greater than 5.5. Time to onset of 24-week confirmed disability improvement was analyzed in patients with a baseline EDSS score of 2.0 or greater.
More than 89% of patients who entered the open-label extension period completed two years of the open-label extension. The group that started and continued ocrelizumab (n = 454), compared with the group that switched from interferon beta-1a to ocrelizumab (n = 419), had a higher proportion of patients with 24-week confirmed disability improvement in the year before the switch (16.8% vs 13.3%). At year 1 of the extension, the group that started and continued ocrelizumab included 399 participants, and 20.6% had 24-week confirmed disability improvement, compared with 16.6% of the group that switched from interferon beta-1a to ocrelizumab, which included 366 participants. At year 2, the former group included 363 patients, and 23.7% had 24-week confirmed disability improvement. The latter group included 339 participants, and 18.9% of them achieved this outcome.
Analyzing Four Years of Treatment
When the investigators examined data for four years of treatment (ie, the double-blind and extension phases), they observed that between 20% and 25% of patients with an EDSS score of 2 or more who received ocrelizumab had improvement in EDSS score. When they examined patients with EDSS scores lower than 2, the results were similar. “This [finding] parallels some of the effects that we see in clinical efficacy, based upon a reduction in MRI parameters such as T1 and T2 lesions,” said Dr. Naismith.
“What we are seeing, especially with some of our high-efficacy therapies, is that patients come back and report that they are feeling better in subsequent visits. I admit, I never tell patients that this is an expectation they should have…. But it is always nice to hear from a patient that they are doing better in some tangible way in their lives,” Dr. Naismith concluded.
—Erik Greb
This outcome remains more likely in patients who started on ocrelizumab than in those who switched to it from interferon beta.
This outcome remains more likely in patients who started on ocrelizumab than in those who switched to it from interferon beta.
NASHVILLE—The benefits of ocrelizumab on 24-week confirmed disability improvement, which were demonstrated in two-year, double-blind, controlled trials, were maintained for two years in an open-label extension study in patients with relapsing-remitting multiple sclerosis (MS), according to data described at the 2018 CMSC Annual Meeting.
The 96-week, double-blind, controlled periods of the OPERA I and II trials demonstrated the efficacy and safety of ocrelizumab in relapsing-remitting MS. Upon completion of the controlled treatment periods, all patients were eligible to enter an open-label extension phase during which they would receive ocrelizumab. Robert T. Naismith, MD, Associate Professor of Neurology at Washington University School of Medicine in St. Louis, and colleagues reviewed data from this extension phase to assess the effect of switching to ocrelizumab or maintaining ocrelizumab therapy on the proportion of patients experiencing disability improvement.
Difference Between Groups Endured
During the controlled treatment period, patients received IV ocrelizumab (600 mg) every 24 weeks or subcutaneous interferon beta-1a (44 μg) three times weekly for 96 weeks. At the start of the open-label extension period, patients continued ocrelizumab or were switched from interferon beta-1a to ocrelizumab. Disability improvement compared with baseline was defined as a reduction in Expanded Disability Status Scale (EDSS) score of 1.0 or more points for patients with a baseline EDSS score from 2.0 to 5.5, or a reduction of 0.5 or more points for patients with a baseline EDSS score greater than 5.5. Time to onset of 24-week confirmed disability improvement was analyzed in patients with a baseline EDSS score of 2.0 or greater.
More than 89% of patients who entered the open-label extension period completed two years of the open-label extension. The group that started and continued ocrelizumab (n = 454), compared with the group that switched from interferon beta-1a to ocrelizumab (n = 419), had a higher proportion of patients with 24-week confirmed disability improvement in the year before the switch (16.8% vs 13.3%). At year 1 of the extension, the group that started and continued ocrelizumab included 399 participants, and 20.6% had 24-week confirmed disability improvement, compared with 16.6% of the group that switched from interferon beta-1a to ocrelizumab, which included 366 participants. At year 2, the former group included 363 patients, and 23.7% had 24-week confirmed disability improvement. The latter group included 339 participants, and 18.9% of them achieved this outcome.
Analyzing Four Years of Treatment
When the investigators examined data for four years of treatment (ie, the double-blind and extension phases), they observed that between 20% and 25% of patients with an EDSS score of 2 or more who received ocrelizumab had improvement in EDSS score. When they examined patients with EDSS scores lower than 2, the results were similar. “This [finding] parallels some of the effects that we see in clinical efficacy, based upon a reduction in MRI parameters such as T1 and T2 lesions,” said Dr. Naismith.
“What we are seeing, especially with some of our high-efficacy therapies, is that patients come back and report that they are feeling better in subsequent visits. I admit, I never tell patients that this is an expectation they should have…. But it is always nice to hear from a patient that they are doing better in some tangible way in their lives,” Dr. Naismith concluded.
—Erik Greb
NASHVILLE—The benefits of ocrelizumab on 24-week confirmed disability improvement, which were demonstrated in two-year, double-blind, controlled trials, were maintained for two years in an open-label extension study in patients with relapsing-remitting multiple sclerosis (MS), according to data described at the 2018 CMSC Annual Meeting.
The 96-week, double-blind, controlled periods of the OPERA I and II trials demonstrated the efficacy and safety of ocrelizumab in relapsing-remitting MS. Upon completion of the controlled treatment periods, all patients were eligible to enter an open-label extension phase during which they would receive ocrelizumab. Robert T. Naismith, MD, Associate Professor of Neurology at Washington University School of Medicine in St. Louis, and colleagues reviewed data from this extension phase to assess the effect of switching to ocrelizumab or maintaining ocrelizumab therapy on the proportion of patients experiencing disability improvement.
Difference Between Groups Endured
During the controlled treatment period, patients received IV ocrelizumab (600 mg) every 24 weeks or subcutaneous interferon beta-1a (44 μg) three times weekly for 96 weeks. At the start of the open-label extension period, patients continued ocrelizumab or were switched from interferon beta-1a to ocrelizumab. Disability improvement compared with baseline was defined as a reduction in Expanded Disability Status Scale (EDSS) score of 1.0 or more points for patients with a baseline EDSS score from 2.0 to 5.5, or a reduction of 0.5 or more points for patients with a baseline EDSS score greater than 5.5. Time to onset of 24-week confirmed disability improvement was analyzed in patients with a baseline EDSS score of 2.0 or greater.
More than 89% of patients who entered the open-label extension period completed two years of the open-label extension. The group that started and continued ocrelizumab (n = 454), compared with the group that switched from interferon beta-1a to ocrelizumab (n = 419), had a higher proportion of patients with 24-week confirmed disability improvement in the year before the switch (16.8% vs 13.3%). At year 1 of the extension, the group that started and continued ocrelizumab included 399 participants, and 20.6% had 24-week confirmed disability improvement, compared with 16.6% of the group that switched from interferon beta-1a to ocrelizumab, which included 366 participants. At year 2, the former group included 363 patients, and 23.7% had 24-week confirmed disability improvement. The latter group included 339 participants, and 18.9% of them achieved this outcome.
Analyzing Four Years of Treatment
When the investigators examined data for four years of treatment (ie, the double-blind and extension phases), they observed that between 20% and 25% of patients with an EDSS score of 2 or more who received ocrelizumab had improvement in EDSS score. When they examined patients with EDSS scores lower than 2, the results were similar. “This [finding] parallels some of the effects that we see in clinical efficacy, based upon a reduction in MRI parameters such as T1 and T2 lesions,” said Dr. Naismith.
“What we are seeing, especially with some of our high-efficacy therapies, is that patients come back and report that they are feeling better in subsequent visits. I admit, I never tell patients that this is an expectation they should have…. But it is always nice to hear from a patient that they are doing better in some tangible way in their lives,” Dr. Naismith concluded.
—Erik Greb
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
Can Neurologists Predict a Patient’s Nonadherence to DMTs for MS?
NASHVILLE—Demographic characteristics, comorbidities, and previous treatments can predict intentional and unintentional nonadherence to disease-modifying therapy (DMT) for multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting. Neurologists should consider risk factors for nonadherence to treatment when selecting an appropriate therapy, said the researchers.
Approximately 33% of patients with MS do not adhere to their DMT regimens. Nonadherence results in suboptimal therapeutic efficacy and increased disability and costs. Unintentional nonadherence may result from cognitive impairment or circumstances that the patient does not control directly. Intentional nonadherence, on the other hand, involves a deliberate decision not to take prescribed medication as directed. Factors that predict patient nonadherence to treatment, whether intentional or unintentional, could affect the choice of DMT.
An Observational Study
Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues sought to explore factors associated with intentional and unintentional nonadherence to DMT in patients with MS. They conducted an observational, cross-sectional study of patient-reported outcomes (PROs) obtained at a single MS center in the United States during routine clinical care. The assessments included standardized, validated, computerized cognitive testing (NeuroTrax); Expanded Disability Status Scale (EDSS) score; and PROs (ie, Beck Depression Inventory [BDI], Modified Fatigue Impact Scale [MFIS], and Morisky Medication Adherence Scale [MMAS-8]). The investigators also obtained demographic data such as age, gender, marital status, employment, driving capability, and prior DMTs. Patients receiving an infused DMT were excluded from the study.
Of 499 patients, 273 (54.7%) met the inclusion criteria. About 76% of participants were female, and the population’s average age was 49. Of the 273 participants, 82 (30.0%) were intentionally nonadherent and 133 (48.7%) were unintentionally nonadherent. Higher depression scores and previous DMTs were associated with a greater risk of intentional nonadherence, as predicted by MMAS-8. Higher MFIS scores were associated with greater risk of unintentional nonadherence.
Increased age was associated with a lower risk of intentional and unintentional nonadherence. EDSS scores, mean NeuroTrax global cognitive summary scores, and MFIS physical subscale scores were not associated with intentional nonadherence. Prior DMT and EDSS scores were not associated with unintentional nonadherence.
How Can Adherence Be Improved?
“Treatment of the underlying cause of nonadherence might be critical to improve quality of life and impact outcomes and adherence,” Dr. Gudesblatt told Neurology Reviews.
“Identifying the risk of nonadherence is critical to the choice of DMT. For example, if self-administered therapy is prescribed to someone who is not adherent, that would be a bad choice,” he added. “If there are multiple risk factors for nonadherence, then the clinician must take this into account in the final discussion of [the] choice … of DMT. This [consideration] will be critical in the long run for preservation of ability and avoiding disability.”
Dr. Gudesblatt and colleagues plan to investigate this topic in longitudinal studies and research the effect of cognition on nonadherence. Neurologists have “so much more to do to better understand patients’ perceptions, improve outcomes, and improve decision making and management,” Dr. Gudesblatt concluded.
—Erik Greb
NASHVILLE—Demographic characteristics, comorbidities, and previous treatments can predict intentional and unintentional nonadherence to disease-modifying therapy (DMT) for multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting. Neurologists should consider risk factors for nonadherence to treatment when selecting an appropriate therapy, said the researchers.
Approximately 33% of patients with MS do not adhere to their DMT regimens. Nonadherence results in suboptimal therapeutic efficacy and increased disability and costs. Unintentional nonadherence may result from cognitive impairment or circumstances that the patient does not control directly. Intentional nonadherence, on the other hand, involves a deliberate decision not to take prescribed medication as directed. Factors that predict patient nonadherence to treatment, whether intentional or unintentional, could affect the choice of DMT.
An Observational Study
Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues sought to explore factors associated with intentional and unintentional nonadherence to DMT in patients with MS. They conducted an observational, cross-sectional study of patient-reported outcomes (PROs) obtained at a single MS center in the United States during routine clinical care. The assessments included standardized, validated, computerized cognitive testing (NeuroTrax); Expanded Disability Status Scale (EDSS) score; and PROs (ie, Beck Depression Inventory [BDI], Modified Fatigue Impact Scale [MFIS], and Morisky Medication Adherence Scale [MMAS-8]). The investigators also obtained demographic data such as age, gender, marital status, employment, driving capability, and prior DMTs. Patients receiving an infused DMT were excluded from the study.
Of 499 patients, 273 (54.7%) met the inclusion criteria. About 76% of participants were female, and the population’s average age was 49. Of the 273 participants, 82 (30.0%) were intentionally nonadherent and 133 (48.7%) were unintentionally nonadherent. Higher depression scores and previous DMTs were associated with a greater risk of intentional nonadherence, as predicted by MMAS-8. Higher MFIS scores were associated with greater risk of unintentional nonadherence.
Increased age was associated with a lower risk of intentional and unintentional nonadherence. EDSS scores, mean NeuroTrax global cognitive summary scores, and MFIS physical subscale scores were not associated with intentional nonadherence. Prior DMT and EDSS scores were not associated with unintentional nonadherence.
How Can Adherence Be Improved?
“Treatment of the underlying cause of nonadherence might be critical to improve quality of life and impact outcomes and adherence,” Dr. Gudesblatt told Neurology Reviews.
“Identifying the risk of nonadherence is critical to the choice of DMT. For example, if self-administered therapy is prescribed to someone who is not adherent, that would be a bad choice,” he added. “If there are multiple risk factors for nonadherence, then the clinician must take this into account in the final discussion of [the] choice … of DMT. This [consideration] will be critical in the long run for preservation of ability and avoiding disability.”
Dr. Gudesblatt and colleagues plan to investigate this topic in longitudinal studies and research the effect of cognition on nonadherence. Neurologists have “so much more to do to better understand patients’ perceptions, improve outcomes, and improve decision making and management,” Dr. Gudesblatt concluded.
—Erik Greb
NASHVILLE—Demographic characteristics, comorbidities, and previous treatments can predict intentional and unintentional nonadherence to disease-modifying therapy (DMT) for multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting. Neurologists should consider risk factors for nonadherence to treatment when selecting an appropriate therapy, said the researchers.
Approximately 33% of patients with MS do not adhere to their DMT regimens. Nonadherence results in suboptimal therapeutic efficacy and increased disability and costs. Unintentional nonadherence may result from cognitive impairment or circumstances that the patient does not control directly. Intentional nonadherence, on the other hand, involves a deliberate decision not to take prescribed medication as directed. Factors that predict patient nonadherence to treatment, whether intentional or unintentional, could affect the choice of DMT.
An Observational Study
Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues sought to explore factors associated with intentional and unintentional nonadherence to DMT in patients with MS. They conducted an observational, cross-sectional study of patient-reported outcomes (PROs) obtained at a single MS center in the United States during routine clinical care. The assessments included standardized, validated, computerized cognitive testing (NeuroTrax); Expanded Disability Status Scale (EDSS) score; and PROs (ie, Beck Depression Inventory [BDI], Modified Fatigue Impact Scale [MFIS], and Morisky Medication Adherence Scale [MMAS-8]). The investigators also obtained demographic data such as age, gender, marital status, employment, driving capability, and prior DMTs. Patients receiving an infused DMT were excluded from the study.
Of 499 patients, 273 (54.7%) met the inclusion criteria. About 76% of participants were female, and the population’s average age was 49. Of the 273 participants, 82 (30.0%) were intentionally nonadherent and 133 (48.7%) were unintentionally nonadherent. Higher depression scores and previous DMTs were associated with a greater risk of intentional nonadherence, as predicted by MMAS-8. Higher MFIS scores were associated with greater risk of unintentional nonadherence.
Increased age was associated with a lower risk of intentional and unintentional nonadherence. EDSS scores, mean NeuroTrax global cognitive summary scores, and MFIS physical subscale scores were not associated with intentional nonadherence. Prior DMT and EDSS scores were not associated with unintentional nonadherence.
How Can Adherence Be Improved?
“Treatment of the underlying cause of nonadherence might be critical to improve quality of life and impact outcomes and adherence,” Dr. Gudesblatt told Neurology Reviews.
“Identifying the risk of nonadherence is critical to the choice of DMT. For example, if self-administered therapy is prescribed to someone who is not adherent, that would be a bad choice,” he added. “If there are multiple risk factors for nonadherence, then the clinician must take this into account in the final discussion of [the] choice … of DMT. This [consideration] will be critical in the long run for preservation of ability and avoiding disability.”
Dr. Gudesblatt and colleagues plan to investigate this topic in longitudinal studies and research the effect of cognition on nonadherence. Neurologists have “so much more to do to better understand patients’ perceptions, improve outcomes, and improve decision making and management,” Dr. Gudesblatt concluded.
—Erik Greb
How Does the Gut Microbiome Differ in Patients With Relapsing MS Versus Controls?
NASHVILLE—The microbiome composition of patients with multiple sclerosis (MS) may differ significantly from that of healthy controls, according to data presented at the 2018 CMSC Annual Meeting.
Although the etiology of MS remains unknown, genetic and environmental factors play a role. Evidence from animal models has suggested that alteration of the gut microbiota may modulate immune-mediated demyelination, suggesting a role of the microbiome in MS pathogenesis.
To examine the gut microbiome in patients with relapsing MS versus controls, Raffaella Umeton, MD, Neurology Resident Physician at the University of Massachusetts Memorial Medical Center in Worcester, and colleagues collected 42 stool samples from patients with relapsing-remitting MS and secondary progressive MS with relapses, as well as 28 control samples from healthy donors.
Investigators obtained demographic and clinical data from medical record review and extracted DNA from stool samples. Their statistical analyses included Quantitative Insights Into Microbial Ecology (QIIME) for comparing operational taxonomic unit representation at the species, genus, and family levels.
Ruminococcus torques, Ruminococcus obeum, and Lactospiraces bacterium showed a significantly higher abundance in the relapsing-remitting MS population, compared with healthy controls, and these associations were confirmed at the genus level. Associations with Escherichia coli and Oscillibacter also were significant and confirmed at the genus and family levels.
Bacteroides fragilis and Roseburia were more abundant in healthy donors than in patients with relapsing-remitting MS, and Haemophilus parainfluenzae and Sutterella wadsworthensis were more abundant in healthy donors at the species, genus, and family levels.
“Larger studies are necessary to investigate the changes within the gut microbiome and MS, which may lead to potential disease activity biomarkers and therapies,” Dr. Umeton and colleagues concluded.
—Erica Tricarico
NASHVILLE—The microbiome composition of patients with multiple sclerosis (MS) may differ significantly from that of healthy controls, according to data presented at the 2018 CMSC Annual Meeting.
Although the etiology of MS remains unknown, genetic and environmental factors play a role. Evidence from animal models has suggested that alteration of the gut microbiota may modulate immune-mediated demyelination, suggesting a role of the microbiome in MS pathogenesis.
To examine the gut microbiome in patients with relapsing MS versus controls, Raffaella Umeton, MD, Neurology Resident Physician at the University of Massachusetts Memorial Medical Center in Worcester, and colleagues collected 42 stool samples from patients with relapsing-remitting MS and secondary progressive MS with relapses, as well as 28 control samples from healthy donors.
Investigators obtained demographic and clinical data from medical record review and extracted DNA from stool samples. Their statistical analyses included Quantitative Insights Into Microbial Ecology (QIIME) for comparing operational taxonomic unit representation at the species, genus, and family levels.
Ruminococcus torques, Ruminococcus obeum, and Lactospiraces bacterium showed a significantly higher abundance in the relapsing-remitting MS population, compared with healthy controls, and these associations were confirmed at the genus level. Associations with Escherichia coli and Oscillibacter also were significant and confirmed at the genus and family levels.
Bacteroides fragilis and Roseburia were more abundant in healthy donors than in patients with relapsing-remitting MS, and Haemophilus parainfluenzae and Sutterella wadsworthensis were more abundant in healthy donors at the species, genus, and family levels.
“Larger studies are necessary to investigate the changes within the gut microbiome and MS, which may lead to potential disease activity biomarkers and therapies,” Dr. Umeton and colleagues concluded.
—Erica Tricarico
NASHVILLE—The microbiome composition of patients with multiple sclerosis (MS) may differ significantly from that of healthy controls, according to data presented at the 2018 CMSC Annual Meeting.
Although the etiology of MS remains unknown, genetic and environmental factors play a role. Evidence from animal models has suggested that alteration of the gut microbiota may modulate immune-mediated demyelination, suggesting a role of the microbiome in MS pathogenesis.
To examine the gut microbiome in patients with relapsing MS versus controls, Raffaella Umeton, MD, Neurology Resident Physician at the University of Massachusetts Memorial Medical Center in Worcester, and colleagues collected 42 stool samples from patients with relapsing-remitting MS and secondary progressive MS with relapses, as well as 28 control samples from healthy donors.
Investigators obtained demographic and clinical data from medical record review and extracted DNA from stool samples. Their statistical analyses included Quantitative Insights Into Microbial Ecology (QIIME) for comparing operational taxonomic unit representation at the species, genus, and family levels.
Ruminococcus torques, Ruminococcus obeum, and Lactospiraces bacterium showed a significantly higher abundance in the relapsing-remitting MS population, compared with healthy controls, and these associations were confirmed at the genus level. Associations with Escherichia coli and Oscillibacter also were significant and confirmed at the genus and family levels.
Bacteroides fragilis and Roseburia were more abundant in healthy donors than in patients with relapsing-remitting MS, and Haemophilus parainfluenzae and Sutterella wadsworthensis were more abundant in healthy donors at the species, genus, and family levels.
“Larger studies are necessary to investigate the changes within the gut microbiome and MS, which may lead to potential disease activity biomarkers and therapies,” Dr. Umeton and colleagues concluded.
—Erica Tricarico
A Mediterranean Diet May Be Associated With Lower Depression and Cognitive Impairment Scores in Patients With MS
NASHVILLE—Adherence to a Mediterranean-style diet may be associated with less severe depressive and cognitive impairment symptoms among patients with multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting.
Symptoms of depression, fatigue, and cognitive impairment are common among people with MS and adversely affect quality of life. In the general population, adherence to a Mediterranean-style diet has been associated with improvements in mood, fatigue, and cognitive impairment. It unknown, however, if similar associations exist in the MS population.
To study this question, Leah Mische, a medical student at the Johns Hopkins University School of Medicine in Baltimore, and colleagues assessed the associations between adherence to a Mediterranean-style diet and self-reported symptoms of depression, fatigue, and cognitive impairment in patients with MS.
Thirty-four patients with MS completed a 24-hour dietary recall. Researchers used the responses to quantify patients’ adherence to a Mediterranean-style diet using a validated scoring approach that incorporates high intakes of fruits, vegetables, whole grains, seafood, polyunsaturated fat, and nuts and legumes, low intakes of red and processed meats, and moderate alcohol consumption.
Patients with a greater than median intake of each food group received 1 point. Scores for red and processed meats (where lower intakes are desired) were reversed, and those with moderate alcohol consumption also received 1 point.
The investigators obtained overall Mediterranean diet scores, which ranged from 0 (poor diet quality) to 8 (high diet quality), by summing up individual food group points. In addition, participants provided information about depression, fatigue, and cognitive impairment symptoms by completing Neuro-Quality of Life subscales. Finally, the researchers assessed the association between Mediterranean diet scores and Neuro-Quality of Life subscales using Spearman correlations and linear regression models adjusted for age and sex.
The mean age of participants was 44.6, and 67% were female. Higher Mediterranean diet scores were associated with less severe depressive and cognitive impairment symptoms. In addition, patients in the top tertile of Mediterranean diet scores had a significantly lower average depressive symptoms score, compared with those in the bottom tertile (mean difference, 4.1). Mediterranean diet scores were not associated with fatigue severity.
“Interventional studies are needed to determine the directionality of this relationship,” Ms. Mische and colleagues concluded.
—Erica Tricarico
NASHVILLE—Adherence to a Mediterranean-style diet may be associated with less severe depressive and cognitive impairment symptoms among patients with multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting.
Symptoms of depression, fatigue, and cognitive impairment are common among people with MS and adversely affect quality of life. In the general population, adherence to a Mediterranean-style diet has been associated with improvements in mood, fatigue, and cognitive impairment. It unknown, however, if similar associations exist in the MS population.
To study this question, Leah Mische, a medical student at the Johns Hopkins University School of Medicine in Baltimore, and colleagues assessed the associations between adherence to a Mediterranean-style diet and self-reported symptoms of depression, fatigue, and cognitive impairment in patients with MS.
Thirty-four patients with MS completed a 24-hour dietary recall. Researchers used the responses to quantify patients’ adherence to a Mediterranean-style diet using a validated scoring approach that incorporates high intakes of fruits, vegetables, whole grains, seafood, polyunsaturated fat, and nuts and legumes, low intakes of red and processed meats, and moderate alcohol consumption.
Patients with a greater than median intake of each food group received 1 point. Scores for red and processed meats (where lower intakes are desired) were reversed, and those with moderate alcohol consumption also received 1 point.
The investigators obtained overall Mediterranean diet scores, which ranged from 0 (poor diet quality) to 8 (high diet quality), by summing up individual food group points. In addition, participants provided information about depression, fatigue, and cognitive impairment symptoms by completing Neuro-Quality of Life subscales. Finally, the researchers assessed the association between Mediterranean diet scores and Neuro-Quality of Life subscales using Spearman correlations and linear regression models adjusted for age and sex.
The mean age of participants was 44.6, and 67% were female. Higher Mediterranean diet scores were associated with less severe depressive and cognitive impairment symptoms. In addition, patients in the top tertile of Mediterranean diet scores had a significantly lower average depressive symptoms score, compared with those in the bottom tertile (mean difference, 4.1). Mediterranean diet scores were not associated with fatigue severity.
“Interventional studies are needed to determine the directionality of this relationship,” Ms. Mische and colleagues concluded.
—Erica Tricarico
NASHVILLE—Adherence to a Mediterranean-style diet may be associated with less severe depressive and cognitive impairment symptoms among patients with multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting.
Symptoms of depression, fatigue, and cognitive impairment are common among people with MS and adversely affect quality of life. In the general population, adherence to a Mediterranean-style diet has been associated with improvements in mood, fatigue, and cognitive impairment. It unknown, however, if similar associations exist in the MS population.
To study this question, Leah Mische, a medical student at the Johns Hopkins University School of Medicine in Baltimore, and colleagues assessed the associations between adherence to a Mediterranean-style diet and self-reported symptoms of depression, fatigue, and cognitive impairment in patients with MS.
Thirty-four patients with MS completed a 24-hour dietary recall. Researchers used the responses to quantify patients’ adherence to a Mediterranean-style diet using a validated scoring approach that incorporates high intakes of fruits, vegetables, whole grains, seafood, polyunsaturated fat, and nuts and legumes, low intakes of red and processed meats, and moderate alcohol consumption.
Patients with a greater than median intake of each food group received 1 point. Scores for red and processed meats (where lower intakes are desired) were reversed, and those with moderate alcohol consumption also received 1 point.
The investigators obtained overall Mediterranean diet scores, which ranged from 0 (poor diet quality) to 8 (high diet quality), by summing up individual food group points. In addition, participants provided information about depression, fatigue, and cognitive impairment symptoms by completing Neuro-Quality of Life subscales. Finally, the researchers assessed the association between Mediterranean diet scores and Neuro-Quality of Life subscales using Spearman correlations and linear regression models adjusted for age and sex.
The mean age of participants was 44.6, and 67% were female. Higher Mediterranean diet scores were associated with less severe depressive and cognitive impairment symptoms. In addition, patients in the top tertile of Mediterranean diet scores had a significantly lower average depressive symptoms score, compared with those in the bottom tertile (mean difference, 4.1). Mediterranean diet scores were not associated with fatigue severity.
“Interventional studies are needed to determine the directionality of this relationship,” Ms. Mische and colleagues concluded.
—Erica Tricarico