MDedge Neurology

DENVER – Multiple treatment transitions in patients with neuromyelitis optica spectrum disorder (NMOSD) for nonmedical reasons are associated with increased neurological harm, including relapse risk and disease progression, new research shows.

“For the first time, we were able to quantify clinical outcomes associated with treatment transitions in people with NMOSD. Our data highlight that aspects outside of therapeutic efficacy may be remarkably meaningful in the effective suppression of disease advancement,” said senior investigator Darin T. Okuda, MD, professor of neurology and director of the neuroinnovation program at University of Texas Southwestern Medical Center in Dallas.

The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Treatment delayed?

NMOSD, an inflammatory syndrome of the central nervous system, can cause irreversible disability. As treatments have improved over time, transitioning from one medication to newer options has become increasingly common.

To better understand the effects of multiple treatment transitions, the researchers conducted a retrospective analysis of electronic medical records of 164 patients with aquaporin-4 IgG–positive NMOSD. Of these individuals, 89 met the study’s inclusion criteria.

Of the participants, 89% were female, and the median disease duration was 10.1 years. Forty-two patients had switched therapies at least once; 26 switched at least twice; 12 switched at least three times; six switched four times; and three switched therapies five times or more for a total of 174 treatment transitions.

Patients were stratified into two groups – those who transitioned for medical reasons (53.4%), and those who switched because of nonmedical/tolerability reasons (46.6%).

Top reasons for transitioning in the medical category included clinical relapse and/or new MRI activity (29.9%), physician-directed transition (11.5%), and increased physical or clinical disability (4.0%). Leading reasons for nonmedical transitions were side effects (16.7%), adherence/persistence (8.1%), and cost/access (5.75%).

A recurrent event survival analysis showed that, after just one transition for nonmedical or tolerability reasons, outcomes significantly improved, with the risk of hospitalization decreasing 40.3% (P = .005), the risk of relapse decreasing by 53.1% (P = .002), and the risk of advancement on MRI decreasing by 65.9% (P = .005).

Conversely, each additional drug discontinuation in the nonmedical group was associated with worse outcomes. These included a 25.2% increased risk of hospitalization (P = .0003), a 24.4% increase in relapse risk (P = .06), and a 41.9% increased risk of MRI advancement (P = .03).

In terms of transitions for medical reasons, there was a significantly increased risk of MRI advancement with the first switch (32.2%; P = .005). However, no significant increases in risk were associated with each additional transition (P = .33).

The median time spent on the first treatment was 306 days in the transition for medical reasons group and 378 days for the nonmedical/tolerability group.

The median duration of time spent between treatments during the initial transition was just 7 days among those transitioning for medical reasons versus 91 days for nonmedical reasons, with the median duration of additional transitions also substantially longer in the nonmedical reasons group, at 22 and 80 days, respectively.

“The median time spent on a first-line therapy regardless of [whether] that first transition was due to a medical or nonmedical tolerability reason was similar; however, the duration of that initial transition was 13 times longer if the transition had to do with a nonmedical or tolerability reason,” first author Alexander D. Smith, a clinical data specialist at UT Southwestern Medical Center, told conference delegates. “Similarly, each additional transition was almost four times longer if it had to do with a nonmedical or tolerability reason,” he said.

Dr. Okuda noted the longer window between treatment transitions may be a key factor in the different outcomes between the groups. “A central theory involves the increased amount of time between treatments,” he said.

“The reasons for the delay in starting a new treatment may be related to a variety of factors, including laboratory testing required to start a new treatment, third-party administrator coverage, time for the resolution of adverse reactions, and/or personal factors from the individual undergoing treatment, etc.”

Another factor, Mr. Smith said in his talk, is that, “when people are left miserable by a prior treatment exposure, they may simply be hesitant to get on the next therapy.”

The finding that only MRI advancement was associated with transitions for medical reasons suggests that worsening disease activity is not necessarily behind increased transitions, with nonmedical reasons often the cause, and more likely to be associated with the worse outcomes.

With the time between treatments a possible culprit, Dr. Okuda said the clinical implications are that “treatment transitions, regardless of the reason, should occur as quickly as possible to reduce the risk for disease progression associated with NMOSD.”

Mr. Smith echoed the suggestion, adding that “it’s important that even if disease activity is not present, complacency should be avoided.”

“Clinicians and third-party administrators should work to ensure that people with NMOSD have accelerated switches onto their next therapy, even if that disease activity is not present. In a sense, rapid treatment transitions may have equitable benefits to the treatments themselves,” Mr. Smith added.

Important research

Commenting on the study, Shailee Shah, MD, an assistant professor in the Neuroimmunology division at Vanderbilt University Medical Center, in Nashville, Tenn., noted the findings are consistent with generally higher concerns around switching treatments for nonmedical reasons.

“In general, if a high-efficacy medication is started, it appears that patients are less likely to require a transition to a different medication. It is a little harder to predict who may have issues with tolerability or nonmedical reasons to transition medications, and many providers would likely agree that these transitions do raise some concerns about the risk of relapse or hospitalization in the interim,” she said.

Dr. Shah added that in her experience patients who require multiple transitions are either started on lower-efficacy medications at treatment initiation or have highly refractory disease.

The study’s findings underscore that “identifying additional risk factors and underlying reasons for these findings will be imperative in the future,” Dr. Shah said.

The study was supported by Revert Health, a corporation founded by Dr. Okuda. Dr. Okuda reports receiving personal compensation for consulting and advisory services from Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Janssen Pharmaceuticals, Novartis, Osmotica Pharmaceuticals, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, and research support from Biogen, EMD Serono/Merck, and Novartis. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.

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

DENVER – Multiple treatment transitions in patients with neuromyelitis optica spectrum disorder (NMOSD) for nonmedical reasons are associated with increased neurological harm, including relapse risk and disease progression, new research shows.

“For the first time, we were able to quantify clinical outcomes associated with treatment transitions in people with NMOSD. Our data highlight that aspects outside of therapeutic efficacy may be remarkably meaningful in the effective suppression of disease advancement,” said senior investigator Darin T. Okuda, MD, professor of neurology and director of the neuroinnovation program at University of Texas Southwestern Medical Center in Dallas.

The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Treatment delayed?

NMOSD, an inflammatory syndrome of the central nervous system, can cause irreversible disability. As treatments have improved over time, transitioning from one medication to newer options has become increasingly common.

To better understand the effects of multiple treatment transitions, the researchers conducted a retrospective analysis of electronic medical records of 164 patients with aquaporin-4 IgG–positive NMOSD. Of these individuals, 89 met the study’s inclusion criteria.

Of the participants, 89% were female, and the median disease duration was 10.1 years. Forty-two patients had switched therapies at least once; 26 switched at least twice; 12 switched at least three times; six switched four times; and three switched therapies five times or more for a total of 174 treatment transitions.

Patients were stratified into two groups – those who transitioned for medical reasons (53.4%), and those who switched because of nonmedical/tolerability reasons (46.6%).

Top reasons for transitioning in the medical category included clinical relapse and/or new MRI activity (29.9%), physician-directed transition (11.5%), and increased physical or clinical disability (4.0%). Leading reasons for nonmedical transitions were side effects (16.7%), adherence/persistence (8.1%), and cost/access (5.75%).

A recurrent event survival analysis showed that, after just one transition for nonmedical or tolerability reasons, outcomes significantly improved, with the risk of hospitalization decreasing 40.3% (P = .005), the risk of relapse decreasing by 53.1% (P = .002), and the risk of advancement on MRI decreasing by 65.9% (P = .005).

Conversely, each additional drug discontinuation in the nonmedical group was associated with worse outcomes. These included a 25.2% increased risk of hospitalization (P = .0003), a 24.4% increase in relapse risk (P = .06), and a 41.9% increased risk of MRI advancement (P = .03).

In terms of transitions for medical reasons, there was a significantly increased risk of MRI advancement with the first switch (32.2%; P = .005). However, no significant increases in risk were associated with each additional transition (P = .33).

The median time spent on the first treatment was 306 days in the transition for medical reasons group and 378 days for the nonmedical/tolerability group.

The median duration of time spent between treatments during the initial transition was just 7 days among those transitioning for medical reasons versus 91 days for nonmedical reasons, with the median duration of additional transitions also substantially longer in the nonmedical reasons group, at 22 and 80 days, respectively.

“The median time spent on a first-line therapy regardless of [whether] that first transition was due to a medical or nonmedical tolerability reason was similar; however, the duration of that initial transition was 13 times longer if the transition had to do with a nonmedical or tolerability reason,” first author Alexander D. Smith, a clinical data specialist at UT Southwestern Medical Center, told conference delegates. “Similarly, each additional transition was almost four times longer if it had to do with a nonmedical or tolerability reason,” he said.

Dr. Okuda noted the longer window between treatment transitions may be a key factor in the different outcomes between the groups. “A central theory involves the increased amount of time between treatments,” he said.

“The reasons for the delay in starting a new treatment may be related to a variety of factors, including laboratory testing required to start a new treatment, third-party administrator coverage, time for the resolution of adverse reactions, and/or personal factors from the individual undergoing treatment, etc.”

Another factor, Mr. Smith said in his talk, is that, “when people are left miserable by a prior treatment exposure, they may simply be hesitant to get on the next therapy.”

The finding that only MRI advancement was associated with transitions for medical reasons suggests that worsening disease activity is not necessarily behind increased transitions, with nonmedical reasons often the cause, and more likely to be associated with the worse outcomes.

With the time between treatments a possible culprit, Dr. Okuda said the clinical implications are that “treatment transitions, regardless of the reason, should occur as quickly as possible to reduce the risk for disease progression associated with NMOSD.”

Mr. Smith echoed the suggestion, adding that “it’s important that even if disease activity is not present, complacency should be avoided.”

“Clinicians and third-party administrators should work to ensure that people with NMOSD have accelerated switches onto their next therapy, even if that disease activity is not present. In a sense, rapid treatment transitions may have equitable benefits to the treatments themselves,” Mr. Smith added.

Important research

Commenting on the study, Shailee Shah, MD, an assistant professor in the Neuroimmunology division at Vanderbilt University Medical Center, in Nashville, Tenn., noted the findings are consistent with generally higher concerns around switching treatments for nonmedical reasons.

“In general, if a high-efficacy medication is started, it appears that patients are less likely to require a transition to a different medication. It is a little harder to predict who may have issues with tolerability or nonmedical reasons to transition medications, and many providers would likely agree that these transitions do raise some concerns about the risk of relapse or hospitalization in the interim,” she said.

Dr. Shah added that in her experience patients who require multiple transitions are either started on lower-efficacy medications at treatment initiation or have highly refractory disease.

The study’s findings underscore that “identifying additional risk factors and underlying reasons for these findings will be imperative in the future,” Dr. Shah said.

The study was supported by Revert Health, a corporation founded by Dr. Okuda. Dr. Okuda reports receiving personal compensation for consulting and advisory services from Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Janssen Pharmaceuticals, Novartis, Osmotica Pharmaceuticals, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, and research support from Biogen, EMD Serono/Merck, and Novartis. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.

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

DENVER – Multiple treatment transitions in patients with neuromyelitis optica spectrum disorder (NMOSD) for nonmedical reasons are associated with increased neurological harm, including relapse risk and disease progression, new research shows.

“For the first time, we were able to quantify clinical outcomes associated with treatment transitions in people with NMOSD. Our data highlight that aspects outside of therapeutic efficacy may be remarkably meaningful in the effective suppression of disease advancement,” said senior investigator Darin T. Okuda, MD, professor of neurology and director of the neuroinnovation program at University of Texas Southwestern Medical Center in Dallas.

The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Treatment delayed?

NMOSD, an inflammatory syndrome of the central nervous system, can cause irreversible disability. As treatments have improved over time, transitioning from one medication to newer options has become increasingly common.

To better understand the effects of multiple treatment transitions, the researchers conducted a retrospective analysis of electronic medical records of 164 patients with aquaporin-4 IgG–positive NMOSD. Of these individuals, 89 met the study’s inclusion criteria.

Of the participants, 89% were female, and the median disease duration was 10.1 years. Forty-two patients had switched therapies at least once; 26 switched at least twice; 12 switched at least three times; six switched four times; and three switched therapies five times or more for a total of 174 treatment transitions.

Patients were stratified into two groups – those who transitioned for medical reasons (53.4%), and those who switched because of nonmedical/tolerability reasons (46.6%).

Top reasons for transitioning in the medical category included clinical relapse and/or new MRI activity (29.9%), physician-directed transition (11.5%), and increased physical or clinical disability (4.0%). Leading reasons for nonmedical transitions were side effects (16.7%), adherence/persistence (8.1%), and cost/access (5.75%).

A recurrent event survival analysis showed that, after just one transition for nonmedical or tolerability reasons, outcomes significantly improved, with the risk of hospitalization decreasing 40.3% (P = .005), the risk of relapse decreasing by 53.1% (P = .002), and the risk of advancement on MRI decreasing by 65.9% (P = .005).

Conversely, each additional drug discontinuation in the nonmedical group was associated with worse outcomes. These included a 25.2% increased risk of hospitalization (P = .0003), a 24.4% increase in relapse risk (P = .06), and a 41.9% increased risk of MRI advancement (P = .03).

In terms of transitions for medical reasons, there was a significantly increased risk of MRI advancement with the first switch (32.2%; P = .005). However, no significant increases in risk were associated with each additional transition (P = .33).

The median time spent on the first treatment was 306 days in the transition for medical reasons group and 378 days for the nonmedical/tolerability group.

The median duration of time spent between treatments during the initial transition was just 7 days among those transitioning for medical reasons versus 91 days for nonmedical reasons, with the median duration of additional transitions also substantially longer in the nonmedical reasons group, at 22 and 80 days, respectively.

“The median time spent on a first-line therapy regardless of [whether] that first transition was due to a medical or nonmedical tolerability reason was similar; however, the duration of that initial transition was 13 times longer if the transition had to do with a nonmedical or tolerability reason,” first author Alexander D. Smith, a clinical data specialist at UT Southwestern Medical Center, told conference delegates. “Similarly, each additional transition was almost four times longer if it had to do with a nonmedical or tolerability reason,” he said.

Dr. Okuda noted the longer window between treatment transitions may be a key factor in the different outcomes between the groups. “A central theory involves the increased amount of time between treatments,” he said.

“The reasons for the delay in starting a new treatment may be related to a variety of factors, including laboratory testing required to start a new treatment, third-party administrator coverage, time for the resolution of adverse reactions, and/or personal factors from the individual undergoing treatment, etc.”

Another factor, Mr. Smith said in his talk, is that, “when people are left miserable by a prior treatment exposure, they may simply be hesitant to get on the next therapy.”

The finding that only MRI advancement was associated with transitions for medical reasons suggests that worsening disease activity is not necessarily behind increased transitions, with nonmedical reasons often the cause, and more likely to be associated with the worse outcomes.

With the time between treatments a possible culprit, Dr. Okuda said the clinical implications are that “treatment transitions, regardless of the reason, should occur as quickly as possible to reduce the risk for disease progression associated with NMOSD.”

Mr. Smith echoed the suggestion, adding that “it’s important that even if disease activity is not present, complacency should be avoided.”

“Clinicians and third-party administrators should work to ensure that people with NMOSD have accelerated switches onto their next therapy, even if that disease activity is not present. In a sense, rapid treatment transitions may have equitable benefits to the treatments themselves,” Mr. Smith added.

Important research

Commenting on the study, Shailee Shah, MD, an assistant professor in the Neuroimmunology division at Vanderbilt University Medical Center, in Nashville, Tenn., noted the findings are consistent with generally higher concerns around switching treatments for nonmedical reasons.

“In general, if a high-efficacy medication is started, it appears that patients are less likely to require a transition to a different medication. It is a little harder to predict who may have issues with tolerability or nonmedical reasons to transition medications, and many providers would likely agree that these transitions do raise some concerns about the risk of relapse or hospitalization in the interim,” she said.

Dr. Shah added that in her experience patients who require multiple transitions are either started on lower-efficacy medications at treatment initiation or have highly refractory disease.

The study’s findings underscore that “identifying additional risk factors and underlying reasons for these findings will be imperative in the future,” Dr. Shah said.

The study was supported by Revert Health, a corporation founded by Dr. Okuda. Dr. Okuda reports receiving personal compensation for consulting and advisory services from Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Janssen Pharmaceuticals, Novartis, Osmotica Pharmaceuticals, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, and research support from Biogen, EMD Serono/Merck, and Novartis. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.

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

Aurora, Colo. – The access to and quality of multiple sclerosis (MS) care varies substantially depending on a patient’s race, ethnicity, gender, and geography, according to research on patient-reported health inequities presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

”Equal access to and quality of care are critical for managing a progressive disease such as multiple sclerosis,” said Chris Hardy, of Publicis Health Media, and her associates. “Despite increased awareness of health outcome disparities in the U.S., certain patients still experience inequities in care.”

The researchers sent emails to members of MyMSTeam, an online support network of more than 197,000 members, to request completion of a 34-question online survey. Questions addressed respondents’ ability to access care, resources in their neighborhood, and their interactions with their health care providers. Questions also addressed the burden of MS on individuals’ quality of life, which was considerable across all demographics. The 1,935 patients with MS who responded were overwhelmingly White, though the demographics varied by question.
 

A ‘widespread and significant problem’

“This study is important in pointing out the unfortunate, obvious [fact] that lack of access and lack of availability to treatment is still a widespread and significant problem in this country,” commented Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates who was not involved in the study. “Improving effective treatment of disease requires a more granular understanding of disease impact on a quantitative, multidimensional, objective patient-centric approach,” he added. “Racial and ethnic barriers to effective treatment cannot be allowed nor tolerated. We need to be more acutely aware that outreach, digital health, and remote assessments are tools that we need to incorporate to improve access and do better.”

The pervasive impact of MS

Overall, 85% of respondents reported that MS made it harder to do everyday chores, and 84% said their MS made it harder to exercise and interfered with their everyday life. Similarly high proportions of respondents reported that their MS causes them a lot of stress (80%), makes them feel anxious or depressed (77%), disrupts their work/employment (75%), and interferes with their social life (75%). In addition, more than half said their diagnosis negatively affects their family (59%) and makes them feel judged (53%).

Deanne Power, RN, MSCN, the lead nurse care partner at Octave Bioscience, who spoke as a representative of the study authors, said it’s critical that clinicians be aware of the health inequities that exist among their patient population.

“Some patients have lower income or language issues where English is not their primary language, and they don’t have access and are even afraid to call doctor or reach out [for help],” Ms. Power said. “If providers aren’t actively aware of these situations and talk to their patients, they can’t just say, ‘Oh, well, I just want you to go fill this prescription,’ when they don’t have money to put food on their table. Providers have got to know their patients as [more than] just an MS patient. This is a human being in front of you, and you better know what their life is like, because it’s impacting their MS.”
 

Access to care varied by race

Among the 1,906 respondents who answered questions about access to care, 9% were Black, 5% were Hispanic, and the rest were White. In these questions, differences between demographics arose when it came to individuals’ ability to conveniently see an MS specialist and their subsequent use of emergency services. For example, only 64% of Hispanic respondents reported convenient access to a health care provider specializing in MS, compared with 76% of White and 78% of Black respondents.

A significantly higher proportion of Hispanics also reported that they could not take time off from work when they were sick (25%) or to attend a doctor appointment (20%), compared with White (15% and 9%, respectively) and Black (18% and 12%) respondents. Meanwhile, a significantly higher proportion of Hispanics (35%) reported visiting the emergency department in the past year for MS-related issues, compared with White (19%) or Black (25%) respondents.

White respondents consistently had greater convenient access to dental offices, healthy foods, outpatient care, gyms, and parks and trails, compared with Black and Hispanic patients’ access. For example, 85% of White patients had convenient access to dental offices and 72% had access to outpatient care, compared with Black (74% and 65%) and Hispanic (78% and 52%) patients. Two-thirds of Hispanic respondents (67%) reported access to healthy foods and to gyms, parks, or trails, compared with more than three-quarters of both White and Black patients.
 

Other barriers to MS care

Both racial/ethnic and gender disparities emerged in how patients felt treated by their health care providers. Men were significantly more likely (70%) than women (65%) to say their health care provider listens to and understands them. A statistically significant higher proportion of men (71%) also said their clinician explained their MS test results to them, compared with women (62%), and only 28% of women, versus 37% of men, said their provider developed a long-term plan for them.

Anne Foelsch, the vice president of strategic partnerships at MyHealthTeam, who works with the authors, noted the large discrepancy that was seen particularly for Hispanic patients in terms of how they felt treated by their health care provider.

“Doctors might perceive that the relationship is the same with all of their patients when their patients have a very different perception of what that relationship is and whether they’re not being heard,” Ms. Foelsch said. “It’s important that clinicians take a little bit of time and learn a little bit more about a patient’s perspective and what it’s like when they have a chronic condition like MS and how it impacts their life, looking for those nuances that are different based on your ethnicity.”

Just over half of Hispanic patients (54%) said their provider explained their MS test results, compared with nearly two-thirds of White patients (65%) and 61% of Black patients. Hispanic patients were also less likely (55%) to say they felt their provider listens to and understands them than White (67%) or Black (65%) patients. Two-thirds of White respondents (67%) said their doctor recommended regular check-ups, compared with just over half of Black and Hispanic respondents (55%).

Other statistically significant disparities by race/ethnicity, where a higher proportion of White patients responded affirmatively than Black or Hispanic patients, included feeling treated with respect by their health care provider, feeling their provider is nonjudgmental, and saying their provider spends enough time with them, addresses their MS symptoms, and encourages shared decision-making.

“This study nicely documents and points out that despite our best intentions, we need to do much better as a community to help those with chronic and potentially disabling diseases like MS,” Dr. Gudesblatt said. “The racial, ethnic, and gender disparities only result in greater disability and societal costs by those who can least afford it. All therapies fail due to nonadherence, limited access, lack of insurance coverage, limited insurance coverage, high copays, long waits, cultural biases, and more.”

The researchers acknowledged that their survey respondents may not be representative of all patients with MS because the survey relied on those who chose to respond to the online survey.

The study authors were all employees of Publicis Health Media or MyHealthTeam. Dr. Gudesblatt reported no disclosures.
 

Aurora, Colo. – The access to and quality of multiple sclerosis (MS) care varies substantially depending on a patient’s race, ethnicity, gender, and geography, according to research on patient-reported health inequities presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

”Equal access to and quality of care are critical for managing a progressive disease such as multiple sclerosis,” said Chris Hardy, of Publicis Health Media, and her associates. “Despite increased awareness of health outcome disparities in the U.S., certain patients still experience inequities in care.”

The researchers sent emails to members of MyMSTeam, an online support network of more than 197,000 members, to request completion of a 34-question online survey. Questions addressed respondents’ ability to access care, resources in their neighborhood, and their interactions with their health care providers. Questions also addressed the burden of MS on individuals’ quality of life, which was considerable across all demographics. The 1,935 patients with MS who responded were overwhelmingly White, though the demographics varied by question.
 

A ‘widespread and significant problem’

“This study is important in pointing out the unfortunate, obvious [fact] that lack of access and lack of availability to treatment is still a widespread and significant problem in this country,” commented Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates who was not involved in the study. “Improving effective treatment of disease requires a more granular understanding of disease impact on a quantitative, multidimensional, objective patient-centric approach,” he added. “Racial and ethnic barriers to effective treatment cannot be allowed nor tolerated. We need to be more acutely aware that outreach, digital health, and remote assessments are tools that we need to incorporate to improve access and do better.”

The pervasive impact of MS

Overall, 85% of respondents reported that MS made it harder to do everyday chores, and 84% said their MS made it harder to exercise and interfered with their everyday life. Similarly high proportions of respondents reported that their MS causes them a lot of stress (80%), makes them feel anxious or depressed (77%), disrupts their work/employment (75%), and interferes with their social life (75%). In addition, more than half said their diagnosis negatively affects their family (59%) and makes them feel judged (53%).

Deanne Power, RN, MSCN, the lead nurse care partner at Octave Bioscience, who spoke as a representative of the study authors, said it’s critical that clinicians be aware of the health inequities that exist among their patient population.

“Some patients have lower income or language issues where English is not their primary language, and they don’t have access and are even afraid to call doctor or reach out [for help],” Ms. Power said. “If providers aren’t actively aware of these situations and talk to their patients, they can’t just say, ‘Oh, well, I just want you to go fill this prescription,’ when they don’t have money to put food on their table. Providers have got to know their patients as [more than] just an MS patient. This is a human being in front of you, and you better know what their life is like, because it’s impacting their MS.”
 

Access to care varied by race

Among the 1,906 respondents who answered questions about access to care, 9% were Black, 5% were Hispanic, and the rest were White. In these questions, differences between demographics arose when it came to individuals’ ability to conveniently see an MS specialist and their subsequent use of emergency services. For example, only 64% of Hispanic respondents reported convenient access to a health care provider specializing in MS, compared with 76% of White and 78% of Black respondents.

A significantly higher proportion of Hispanics also reported that they could not take time off from work when they were sick (25%) or to attend a doctor appointment (20%), compared with White (15% and 9%, respectively) and Black (18% and 12%) respondents. Meanwhile, a significantly higher proportion of Hispanics (35%) reported visiting the emergency department in the past year for MS-related issues, compared with White (19%) or Black (25%) respondents.

White respondents consistently had greater convenient access to dental offices, healthy foods, outpatient care, gyms, and parks and trails, compared with Black and Hispanic patients’ access. For example, 85% of White patients had convenient access to dental offices and 72% had access to outpatient care, compared with Black (74% and 65%) and Hispanic (78% and 52%) patients. Two-thirds of Hispanic respondents (67%) reported access to healthy foods and to gyms, parks, or trails, compared with more than three-quarters of both White and Black patients.
 

Other barriers to MS care

Both racial/ethnic and gender disparities emerged in how patients felt treated by their health care providers. Men were significantly more likely (70%) than women (65%) to say their health care provider listens to and understands them. A statistically significant higher proportion of men (71%) also said their clinician explained their MS test results to them, compared with women (62%), and only 28% of women, versus 37% of men, said their provider developed a long-term plan for them.

Anne Foelsch, the vice president of strategic partnerships at MyHealthTeam, who works with the authors, noted the large discrepancy that was seen particularly for Hispanic patients in terms of how they felt treated by their health care provider.

“Doctors might perceive that the relationship is the same with all of their patients when their patients have a very different perception of what that relationship is and whether they’re not being heard,” Ms. Foelsch said. “It’s important that clinicians take a little bit of time and learn a little bit more about a patient’s perspective and what it’s like when they have a chronic condition like MS and how it impacts their life, looking for those nuances that are different based on your ethnicity.”

Just over half of Hispanic patients (54%) said their provider explained their MS test results, compared with nearly two-thirds of White patients (65%) and 61% of Black patients. Hispanic patients were also less likely (55%) to say they felt their provider listens to and understands them than White (67%) or Black (65%) patients. Two-thirds of White respondents (67%) said their doctor recommended regular check-ups, compared with just over half of Black and Hispanic respondents (55%).

Other statistically significant disparities by race/ethnicity, where a higher proportion of White patients responded affirmatively than Black or Hispanic patients, included feeling treated with respect by their health care provider, feeling their provider is nonjudgmental, and saying their provider spends enough time with them, addresses their MS symptoms, and encourages shared decision-making.

“This study nicely documents and points out that despite our best intentions, we need to do much better as a community to help those with chronic and potentially disabling diseases like MS,” Dr. Gudesblatt said. “The racial, ethnic, and gender disparities only result in greater disability and societal costs by those who can least afford it. All therapies fail due to nonadherence, limited access, lack of insurance coverage, limited insurance coverage, high copays, long waits, cultural biases, and more.”

The researchers acknowledged that their survey respondents may not be representative of all patients with MS because the survey relied on those who chose to respond to the online survey.

The study authors were all employees of Publicis Health Media or MyHealthTeam. Dr. Gudesblatt reported no disclosures.
 

Aurora, Colo. – The access to and quality of multiple sclerosis (MS) care varies substantially depending on a patient’s race, ethnicity, gender, and geography, according to research on patient-reported health inequities presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

”Equal access to and quality of care are critical for managing a progressive disease such as multiple sclerosis,” said Chris Hardy, of Publicis Health Media, and her associates. “Despite increased awareness of health outcome disparities in the U.S., certain patients still experience inequities in care.”

The researchers sent emails to members of MyMSTeam, an online support network of more than 197,000 members, to request completion of a 34-question online survey. Questions addressed respondents’ ability to access care, resources in their neighborhood, and their interactions with their health care providers. Questions also addressed the burden of MS on individuals’ quality of life, which was considerable across all demographics. The 1,935 patients with MS who responded were overwhelmingly White, though the demographics varied by question.
 

A ‘widespread and significant problem’

“This study is important in pointing out the unfortunate, obvious [fact] that lack of access and lack of availability to treatment is still a widespread and significant problem in this country,” commented Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates who was not involved in the study. “Improving effective treatment of disease requires a more granular understanding of disease impact on a quantitative, multidimensional, objective patient-centric approach,” he added. “Racial and ethnic barriers to effective treatment cannot be allowed nor tolerated. We need to be more acutely aware that outreach, digital health, and remote assessments are tools that we need to incorporate to improve access and do better.”

The pervasive impact of MS

Overall, 85% of respondents reported that MS made it harder to do everyday chores, and 84% said their MS made it harder to exercise and interfered with their everyday life. Similarly high proportions of respondents reported that their MS causes them a lot of stress (80%), makes them feel anxious or depressed (77%), disrupts their work/employment (75%), and interferes with their social life (75%). In addition, more than half said their diagnosis negatively affects their family (59%) and makes them feel judged (53%).

Deanne Power, RN, MSCN, the lead nurse care partner at Octave Bioscience, who spoke as a representative of the study authors, said it’s critical that clinicians be aware of the health inequities that exist among their patient population.

“Some patients have lower income or language issues where English is not their primary language, and they don’t have access and are even afraid to call doctor or reach out [for help],” Ms. Power said. “If providers aren’t actively aware of these situations and talk to their patients, they can’t just say, ‘Oh, well, I just want you to go fill this prescription,’ when they don’t have money to put food on their table. Providers have got to know their patients as [more than] just an MS patient. This is a human being in front of you, and you better know what their life is like, because it’s impacting their MS.”
 

Access to care varied by race

Among the 1,906 respondents who answered questions about access to care, 9% were Black, 5% were Hispanic, and the rest were White. In these questions, differences between demographics arose when it came to individuals’ ability to conveniently see an MS specialist and their subsequent use of emergency services. For example, only 64% of Hispanic respondents reported convenient access to a health care provider specializing in MS, compared with 76% of White and 78% of Black respondents.

A significantly higher proportion of Hispanics also reported that they could not take time off from work when they were sick (25%) or to attend a doctor appointment (20%), compared with White (15% and 9%, respectively) and Black (18% and 12%) respondents. Meanwhile, a significantly higher proportion of Hispanics (35%) reported visiting the emergency department in the past year for MS-related issues, compared with White (19%) or Black (25%) respondents.

White respondents consistently had greater convenient access to dental offices, healthy foods, outpatient care, gyms, and parks and trails, compared with Black and Hispanic patients’ access. For example, 85% of White patients had convenient access to dental offices and 72% had access to outpatient care, compared with Black (74% and 65%) and Hispanic (78% and 52%) patients. Two-thirds of Hispanic respondents (67%) reported access to healthy foods and to gyms, parks, or trails, compared with more than three-quarters of both White and Black patients.
 

Other barriers to MS care

Both racial/ethnic and gender disparities emerged in how patients felt treated by their health care providers. Men were significantly more likely (70%) than women (65%) to say their health care provider listens to and understands them. A statistically significant higher proportion of men (71%) also said their clinician explained their MS test results to them, compared with women (62%), and only 28% of women, versus 37% of men, said their provider developed a long-term plan for them.

Anne Foelsch, the vice president of strategic partnerships at MyHealthTeam, who works with the authors, noted the large discrepancy that was seen particularly for Hispanic patients in terms of how they felt treated by their health care provider.

“Doctors might perceive that the relationship is the same with all of their patients when their patients have a very different perception of what that relationship is and whether they’re not being heard,” Ms. Foelsch said. “It’s important that clinicians take a little bit of time and learn a little bit more about a patient’s perspective and what it’s like when they have a chronic condition like MS and how it impacts their life, looking for those nuances that are different based on your ethnicity.”

Just over half of Hispanic patients (54%) said their provider explained their MS test results, compared with nearly two-thirds of White patients (65%) and 61% of Black patients. Hispanic patients were also less likely (55%) to say they felt their provider listens to and understands them than White (67%) or Black (65%) patients. Two-thirds of White respondents (67%) said their doctor recommended regular check-ups, compared with just over half of Black and Hispanic respondents (55%).

Other statistically significant disparities by race/ethnicity, where a higher proportion of White patients responded affirmatively than Black or Hispanic patients, included feeling treated with respect by their health care provider, feeling their provider is nonjudgmental, and saying their provider spends enough time with them, addresses their MS symptoms, and encourages shared decision-making.

“This study nicely documents and points out that despite our best intentions, we need to do much better as a community to help those with chronic and potentially disabling diseases like MS,” Dr. Gudesblatt said. “The racial, ethnic, and gender disparities only result in greater disability and societal costs by those who can least afford it. All therapies fail due to nonadherence, limited access, lack of insurance coverage, limited insurance coverage, high copays, long waits, cultural biases, and more.”

The researchers acknowledged that their survey respondents may not be representative of all patients with MS because the survey relied on those who chose to respond to the online survey.

The study authors were all employees of Publicis Health Media or MyHealthTeam. Dr. Gudesblatt reported no disclosures.
 

DENVER – The use of the monoclonal antibody satralizumab (Enspryng) for the long-term treatment of anti–aquaporin-4 (AQP4) antibody–positive neuromyelitis optica spectrum disorder (NMOSD) provides sustained freedom from relapse with no new safety concerns over 5 years, new research shows.  

“In long-term observations, we are seeing a nice, sustained suppression of relapses early, as well as late, in treatment,” said study investigator Anthony Traboulsee, MD, University of British Columbia, Vancouver, in presenting the findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“It remains very tolerable with no participants discontinuing because of side effects,” he said. “And importantly, [there are] no signs of a delayed risk of infections for both monotherapy and combination therapy.”

Satralizumab, a monoclonal recycling antibody, targets the interleukin (IL)–6 receptor, which is elevated in the serum and cerebrospinal fluid of patients in NMOSD.

The drug was approved by the Food and Drug Administration in 2020 for the treatment of AQP4 antibody–positive NMOSD after favorable results from two key trials: SAkuraSky and SAkuraStar.

The FDA approval marked satralizumab as the third therapy for NMOSD, following eculizumab (Soliris) and inebilizumab (Uplizna).

Satralizumab is administered in subcutaneous injections every 4 weeks after a run-in period of injections at weeks 0, 2, and 4.

Longest trial to date

To evaluate the drug’s long-term efficacy in the treatment of AQP4 IgG–positive NMOSD, patients from the two previous phase 3 trials were entered into the single arm, open-label SAkuraMoon study and continued treatment with the satralizumab 120 mg injections once monthly, with or without immunosuppressive therapy.

The study included 106 patients (mean age 44 years, 89.6% women), all of whom had received one or more doses of satralizumab by the data cutoff of January 2022.

With a median duration of satralizumab exposure of 5 years, the overall adjusted annualized rate of investigator protocol-defined relapse (ARR) was 0.09.

Longitudinal assessment further showed no significant increase in the relapse rate over the course of the study, with an ARR rate of 0.16 at year 1; 0.10 at year 2; 0.05 at year 3; and 0.07 at year 4.

At week 240 (4.6 years), 72% of satralizumab-treated patients were relapse-free, with 91% free from severe relapse.

In addition, 85% of patients had no sustained disability, as measured by Expanded Disability Status Scale (EDSS) worsening, over the study period.  

Asked if there are potential subgroups of patients who may be more susceptible to the worsening of disability, Dr. Traboulsee responded “not that we can tell as of yet.”

“I would like to explore this further as this is a relatively new observation, and, as far as I know, this is the longest follow-up for an NMO treatment trial cohort,” he said.

Favorable safety profile

The safety profile was also favorable, consistent with results in the earlier trials. The longer exposure to satralizumab was not associated with a higher risk of severe (grade 3 or higher) laboratory changes versus the double-blind studies. “Rates of adverse events and serious adverse events with overall satralizumab treatment were comparable with the double-blind periods,” said Dr. Traboulsee.

“With satralizumab combined with immunosuppressant therapy, we’re not seeing an increased rate of infections, because it’s not an immune suppressant – it doesn’t suppress lymphocytes or lower immunoglobulin,” he added.

While the use of combination therapy has been an important clinical concern, Dr. Traboulsee noted that “this does not appear to be the case with satralizumab when combined with daily prednisone or daily azathioprine.”

“There is no increased risk of infections, compared with placebo, and it interestingly appears lower than patients on prednisone or azathioprine alone,” he said.

While the median follow-up was 5 years, some in the clinical trial population have been on treatment for up to 7.9 years.

“Based on the current safety and efficacy data, they could stay on this therapy indefinitely, in my opinion,” Dr. Traboulsee said.

In addition to its long-term safety and efficacy, satralizumab “is easy for patients to take and does not require access to an infusion center. It’s easy for physicians to monitor safety, especially since no additional vaccinations or precautions are required beyond what is done in routine care.”

“What I conclude from that clinically is that this is a highly effective and safe therapy by itself or in combination with another agent,” Dr. Traboulsee said.

He noted that the lack of a bump in infections is “really encouraging and very important with a chronic disease that affects elderly patients. So far, so good,” he added.

‘A good first-line therapy’

Commenting on the study, Shailee Shah, MD, an assistant professor in the neuroimmunology division at Vanderbilt University Medical Center, Nashville, Tenn., agreed that the findings bode well for satralizumab’s long-term benefits.

“These are promising results and suggest that satralizumab is very effective in the long term, and even when patients relapse, those relapses are less severe than they would likely be if the patient were off therapy,” she said.

She noted that, while the ability to self-administer injections with satralizumab is convenient, preferences vary.

“This is patient dependent,” Dr. Shah said. “For some patients an injectable medication is ideal but for others an infusion medication [such as eculizumab] is preferred.”

Overall, however, Dr. Shah described satralizumab as “a good first-line therapy for patients with NMOSD in addition to eculizumab/ravulizumab and inebilizumab.”

“It is reasonable to consider this medication in isolation or with concomitant immunosuppressive therapy,” she said.

Dr. Traboulsee’s disclosures include relationships with Novartis, Roche, Sanofi (Genzyme), Ingo Kleiter, Alexion, Almirall, Bayer, Biogen, Celgene, Genentech, Hexal, Horizon, Merck, and Sanofi. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.

DENVER – The use of the monoclonal antibody satralizumab (Enspryng) for the long-term treatment of anti–aquaporin-4 (AQP4) antibody–positive neuromyelitis optica spectrum disorder (NMOSD) provides sustained freedom from relapse with no new safety concerns over 5 years, new research shows.  

“In long-term observations, we are seeing a nice, sustained suppression of relapses early, as well as late, in treatment,” said study investigator Anthony Traboulsee, MD, University of British Columbia, Vancouver, in presenting the findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“It remains very tolerable with no participants discontinuing because of side effects,” he said. “And importantly, [there are] no signs of a delayed risk of infections for both monotherapy and combination therapy.”

Satralizumab, a monoclonal recycling antibody, targets the interleukin (IL)–6 receptor, which is elevated in the serum and cerebrospinal fluid of patients in NMOSD.

The drug was approved by the Food and Drug Administration in 2020 for the treatment of AQP4 antibody–positive NMOSD after favorable results from two key trials: SAkuraSky and SAkuraStar.

The FDA approval marked satralizumab as the third therapy for NMOSD, following eculizumab (Soliris) and inebilizumab (Uplizna).

Satralizumab is administered in subcutaneous injections every 4 weeks after a run-in period of injections at weeks 0, 2, and 4.

Longest trial to date

To evaluate the drug’s long-term efficacy in the treatment of AQP4 IgG–positive NMOSD, patients from the two previous phase 3 trials were entered into the single arm, open-label SAkuraMoon study and continued treatment with the satralizumab 120 mg injections once monthly, with or without immunosuppressive therapy.

The study included 106 patients (mean age 44 years, 89.6% women), all of whom had received one or more doses of satralizumab by the data cutoff of January 2022.

With a median duration of satralizumab exposure of 5 years, the overall adjusted annualized rate of investigator protocol-defined relapse (ARR) was 0.09.

Longitudinal assessment further showed no significant increase in the relapse rate over the course of the study, with an ARR rate of 0.16 at year 1; 0.10 at year 2; 0.05 at year 3; and 0.07 at year 4.

At week 240 (4.6 years), 72% of satralizumab-treated patients were relapse-free, with 91% free from severe relapse.

In addition, 85% of patients had no sustained disability, as measured by Expanded Disability Status Scale (EDSS) worsening, over the study period.  

Asked if there are potential subgroups of patients who may be more susceptible to the worsening of disability, Dr. Traboulsee responded “not that we can tell as of yet.”

“I would like to explore this further as this is a relatively new observation, and, as far as I know, this is the longest follow-up for an NMO treatment trial cohort,” he said.

Favorable safety profile

The safety profile was also favorable, consistent with results in the earlier trials. The longer exposure to satralizumab was not associated with a higher risk of severe (grade 3 or higher) laboratory changes versus the double-blind studies. “Rates of adverse events and serious adverse events with overall satralizumab treatment were comparable with the double-blind periods,” said Dr. Traboulsee.

“With satralizumab combined with immunosuppressant therapy, we’re not seeing an increased rate of infections, because it’s not an immune suppressant – it doesn’t suppress lymphocytes or lower immunoglobulin,” he added.

While the use of combination therapy has been an important clinical concern, Dr. Traboulsee noted that “this does not appear to be the case with satralizumab when combined with daily prednisone or daily azathioprine.”

“There is no increased risk of infections, compared with placebo, and it interestingly appears lower than patients on prednisone or azathioprine alone,” he said.

While the median follow-up was 5 years, some in the clinical trial population have been on treatment for up to 7.9 years.

“Based on the current safety and efficacy data, they could stay on this therapy indefinitely, in my opinion,” Dr. Traboulsee said.

In addition to its long-term safety and efficacy, satralizumab “is easy for patients to take and does not require access to an infusion center. It’s easy for physicians to monitor safety, especially since no additional vaccinations or precautions are required beyond what is done in routine care.”

“What I conclude from that clinically is that this is a highly effective and safe therapy by itself or in combination with another agent,” Dr. Traboulsee said.

He noted that the lack of a bump in infections is “really encouraging and very important with a chronic disease that affects elderly patients. So far, so good,” he added.

‘A good first-line therapy’

Commenting on the study, Shailee Shah, MD, an assistant professor in the neuroimmunology division at Vanderbilt University Medical Center, Nashville, Tenn., agreed that the findings bode well for satralizumab’s long-term benefits.

“These are promising results and suggest that satralizumab is very effective in the long term, and even when patients relapse, those relapses are less severe than they would likely be if the patient were off therapy,” she said.

She noted that, while the ability to self-administer injections with satralizumab is convenient, preferences vary.

“This is patient dependent,” Dr. Shah said. “For some patients an injectable medication is ideal but for others an infusion medication [such as eculizumab] is preferred.”

Overall, however, Dr. Shah described satralizumab as “a good first-line therapy for patients with NMOSD in addition to eculizumab/ravulizumab and inebilizumab.”

“It is reasonable to consider this medication in isolation or with concomitant immunosuppressive therapy,” she said.

Dr. Traboulsee’s disclosures include relationships with Novartis, Roche, Sanofi (Genzyme), Ingo Kleiter, Alexion, Almirall, Bayer, Biogen, Celgene, Genentech, Hexal, Horizon, Merck, and Sanofi. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.

DENVER – The use of the monoclonal antibody satralizumab (Enspryng) for the long-term treatment of anti–aquaporin-4 (AQP4) antibody–positive neuromyelitis optica spectrum disorder (NMOSD) provides sustained freedom from relapse with no new safety concerns over 5 years, new research shows.  

“In long-term observations, we are seeing a nice, sustained suppression of relapses early, as well as late, in treatment,” said study investigator Anthony Traboulsee, MD, University of British Columbia, Vancouver, in presenting the findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“It remains very tolerable with no participants discontinuing because of side effects,” he said. “And importantly, [there are] no signs of a delayed risk of infections for both monotherapy and combination therapy.”

Satralizumab, a monoclonal recycling antibody, targets the interleukin (IL)–6 receptor, which is elevated in the serum and cerebrospinal fluid of patients in NMOSD.

The drug was approved by the Food and Drug Administration in 2020 for the treatment of AQP4 antibody–positive NMOSD after favorable results from two key trials: SAkuraSky and SAkuraStar.

The FDA approval marked satralizumab as the third therapy for NMOSD, following eculizumab (Soliris) and inebilizumab (Uplizna).

Satralizumab is administered in subcutaneous injections every 4 weeks after a run-in period of injections at weeks 0, 2, and 4.

Longest trial to date

To evaluate the drug’s long-term efficacy in the treatment of AQP4 IgG–positive NMOSD, patients from the two previous phase 3 trials were entered into the single arm, open-label SAkuraMoon study and continued treatment with the satralizumab 120 mg injections once monthly, with or without immunosuppressive therapy.

The study included 106 patients (mean age 44 years, 89.6% women), all of whom had received one or more doses of satralizumab by the data cutoff of January 2022.

With a median duration of satralizumab exposure of 5 years, the overall adjusted annualized rate of investigator protocol-defined relapse (ARR) was 0.09.

Longitudinal assessment further showed no significant increase in the relapse rate over the course of the study, with an ARR rate of 0.16 at year 1; 0.10 at year 2; 0.05 at year 3; and 0.07 at year 4.

At week 240 (4.6 years), 72% of satralizumab-treated patients were relapse-free, with 91% free from severe relapse.

In addition, 85% of patients had no sustained disability, as measured by Expanded Disability Status Scale (EDSS) worsening, over the study period.  

Asked if there are potential subgroups of patients who may be more susceptible to the worsening of disability, Dr. Traboulsee responded “not that we can tell as of yet.”

“I would like to explore this further as this is a relatively new observation, and, as far as I know, this is the longest follow-up for an NMO treatment trial cohort,” he said.

Favorable safety profile

The safety profile was also favorable, consistent with results in the earlier trials. The longer exposure to satralizumab was not associated with a higher risk of severe (grade 3 or higher) laboratory changes versus the double-blind studies. “Rates of adverse events and serious adverse events with overall satralizumab treatment were comparable with the double-blind periods,” said Dr. Traboulsee.

“With satralizumab combined with immunosuppressant therapy, we’re not seeing an increased rate of infections, because it’s not an immune suppressant – it doesn’t suppress lymphocytes or lower immunoglobulin,” he added.

While the use of combination therapy has been an important clinical concern, Dr. Traboulsee noted that “this does not appear to be the case with satralizumab when combined with daily prednisone or daily azathioprine.”

“There is no increased risk of infections, compared with placebo, and it interestingly appears lower than patients on prednisone or azathioprine alone,” he said.

While the median follow-up was 5 years, some in the clinical trial population have been on treatment for up to 7.9 years.

“Based on the current safety and efficacy data, they could stay on this therapy indefinitely, in my opinion,” Dr. Traboulsee said.

In addition to its long-term safety and efficacy, satralizumab “is easy for patients to take and does not require access to an infusion center. It’s easy for physicians to monitor safety, especially since no additional vaccinations or precautions are required beyond what is done in routine care.”

“What I conclude from that clinically is that this is a highly effective and safe therapy by itself or in combination with another agent,” Dr. Traboulsee said.

He noted that the lack of a bump in infections is “really encouraging and very important with a chronic disease that affects elderly patients. So far, so good,” he added.

‘A good first-line therapy’

Commenting on the study, Shailee Shah, MD, an assistant professor in the neuroimmunology division at Vanderbilt University Medical Center, Nashville, Tenn., agreed that the findings bode well for satralizumab’s long-term benefits.

“These are promising results and suggest that satralizumab is very effective in the long term, and even when patients relapse, those relapses are less severe than they would likely be if the patient were off therapy,” she said.

She noted that, while the ability to self-administer injections with satralizumab is convenient, preferences vary.

“This is patient dependent,” Dr. Shah said. “For some patients an injectable medication is ideal but for others an infusion medication [such as eculizumab] is preferred.”

Overall, however, Dr. Shah described satralizumab as “a good first-line therapy for patients with NMOSD in addition to eculizumab/ravulizumab and inebilizumab.”

“It is reasonable to consider this medication in isolation or with concomitant immunosuppressive therapy,” she said.

Dr. Traboulsee’s disclosures include relationships with Novartis, Roche, Sanofi (Genzyme), Ingo Kleiter, Alexion, Almirall, Bayer, Biogen, Celgene, Genentech, Hexal, Horizon, Merck, and Sanofi. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.

Linda Bluestein remembers all the doctors who missed, ignored, or incompletely diagnosed her chronic illness.

There was the orthopedic surgeon who noted her hyperextended elbows but failed to check any of her other joints. The gastroenterologist who insisted on performing multiple scoping procedures but wouldn’t discuss how to manage her symptoms. The other surgeon who, after performing arthroscopy on her injured knee, yelled at her: “There is nothing wrong with your knee! You’re fine!” in a room full of people.

And then there was the rheumatologist who said: “Oh, you want something to be wrong with you?”

“No,” she replied, “I want an explanation. I want to keep working. I just want to know why these things keep happening to me.”

The medical frustration she experienced was especially difficult because, like her health care providers, Linda Bluestein has an MD after her name. She is a board-certified anesthesiologist and integrative medicine physician.

Living with a chronic illness is a challenge for any patient. But physicians who are diagnosed with chronic conditions face a unique set of personal and professional issues.

Along with the physically demanding schedule of medical practice, they must cope with what many call a “culture of invincibility” within medicine. Doctors are not supposed to get sick. In fact, the unwritten rule is presenteeism – to function without adequate food or sleep and to never prioritize their own self-care over their dedication to their patients.

Whether their conditions are visible, such as muscular dystrophy and multiple sclerosis, or invisible, such as fibromyalgia and mental illnesses – and now, long COVID – these doctors often meet significant stigma. They fight the assumption that they are less capable than their colleagues.

But they also experience an invaluable benefit: They gain firsthand knowledge of the patient experience, a profound understanding which, they say, enhances how they care for their own patients.
 

What it takes to become a doctor when you have a chronic condition

In short, it’s not easy.

Data from the 2018 National Health Interview Survey show that more than half of U.S. adults had at least one of several chronic conditions, including rheumatoid arthritis, asthma, diabetes, hypertension, and kidney problems. Nearly a third of respondents had more than one condition. But fewer than 5% of medical students and 3% of practicing physicians report having a chronic illness or disability, according to studies from 2019 and 2021.

While that could mean that fewer people with chronic illness enter medicine, cases also exist in which aspiring physicians with conditions were dissuaded from pursuing a career in medicine at all.

Amy Stenehjem, MD, a physical medicine and rehabilitation physician, is one of the exceptions. Diagnosed with several autoimmune-related conditions as a teenager and young adult, Dr. Stenehjem was determined to become a doctor. In her 20s, her health was relatively stable, and she was able to manage medical school and residency. Her training institutions agreed to provide some accommodations that helped her succeed.

“They let me build some flexibility into the training,” Dr. Stenehjem said. “In medical school, when I knew I wasn’t going to be able to do a particular specialty as a career, they let me work with an attending doctor that did not require a lot of on-call time during that particular rotation.”

Dr. Stenehjem specialized in chronic neck and back disorders, fibromyalgia, chronic fatigue syndrome (myalgic encephalomyelitis), and autoimmune-related diseases. She practiced for more than a decade. But in 2011, her condition spiraled. She couldn’t walk a few steps or even sit upright without experiencing dizziness and shortness of breath. She had debilitating fatigue and episodes of fever, rash, headaches, and joint pain.

It would take 7 years and more than 20 doctors to determine Dr. Stenehjem’s multiple diagnoses. In addition to her autoimmune diseases, she was diagnosed with postural orthostatic tachycardia syndrome, autoinflammatory periodic fever syndrome, Lyme disease, and reactivated Epstein-Barr infection.

While she suspects that her providers gave her more “leeway” because she was a physician, many did not show a deep understanding of the severity of her symptoms and the impact those symptoms had.

“When I was practicing, I really didn’t fully understand the impact chronic illness had on my patients,” Dr. Stenehjem said. “Things like chronic dizziness, headaches, fatigue, pain, or brain fog can be really hard to understand unless you’ve experienced these symptoms. When I got sick, I finally realized, ‘Oh my goodness, when a patient says they’re dealing with fatigue, this is not your normal, I’m-super-tired-from-being-on-call fatigue. This is I-can’t-get-out-of-bed fatigue.’ That’s what people with chronic illness often deal with on a daily basis.”
 

Treating the individual

Dr. Stenehjem was aware that her chronic illness would affect her medical career. For Jason Baker, MD, an endocrinologist at Weill Cornell Medicine, New York, it came as a shock. Dr. Baker was a third-year medical student when he experienced increased urination and rapid weight loss. It was only when friends pressed him to visit student health that a blood test revealed type 1 diabetes. Dr. Baker suddenly found himself lying in a hospital bed.

He remembers an attending physician who simply handed him a textbook on diabetic ketoacidosis (DKA) and a resident who informed him that he had kidney damage, which turned out to be untrue. Neither discussed the psychological issues from a frightening diagnosis that would require lifelong, daily management.

“There certainly could have been a bit more empathy from some of the people I dealt with early on,” he said.

Although his training gave him a stark picture of worst-case scenarios, Dr. Baker found that knowledge motivating. “I’d already seen patients come in who had diabetes complications,” Dr. Baker says. “I vowed to never ever get those complications. It was a good balance of fear and motivation.”

Dr. Baker had not planned to specialize in endocrinology, but he quickly realized that his personal diagnosis could help others. Now he often shares his experience with his patients who have diabetes, which he says makes them more comfortable discussing their own problems.

His approach, Dr. Baker explained, is to treat everyone as an individual. Trying to neatly classify patients with chronic illness is a common mistake he notices among physicians.

“There’s a lot of misunderstanding about type 1 versus type 2 [diabetes],” Dr. Baker said, “and trying to categorize people when sometimes people can’t be categorized. That’s really with any chronic condition; there’s no one size fits all.”

Managing his health is still a time-consuming task. At work, he needs breaks to eat, check his blood sugar, or take insulin. “During the workday seeing patients, I have to also remember that I’m a patient,” Dr. Baker said. “I have to be okay with prioritizing my own health. Otherwise I can’t help anybody.”
 

‘I am not the doctor for you’

Chronic diseases such as diabetes or hypertension are familiar to most doctors, and with good management, patients can usually function normally. When chronic conditions become disabling, however, attitudes in the medical field can change.

According to data from the Centers for Disease Control and Prevention and from studies, people with disabilities experience significant disparities and barriers to care. Some of this can be linked to social determinants of health. People with disabilities are more likely to be poor and to rely on Medicare and Medicaid for insurance coverage. But lack of training, unwillingness to provide accommodations, ignorance of legal requirements, and inaccurate assumptions among physicians also play a role.

These are themes that Lisa Iezzoni, MD, a professor of medicine at Harvard Medical School, Boston, has heard from hundreds of patients with disabilities during the more than 25 years that she has conducted research.

In late 2019, Dr. Iezzoni and coinvestigators fielded a national survey of 714 practicing physicians. Only 40.7% reported they were “very confident” that they could provide the same quality of care to patients with disabilities as they do for other patients. And only 56.5% “strongly agreed” that they welcomed these patients into their practices.

The survey was conducted through a series of small focus groups that Dr. Iezzoni held with physicians in 2018. These yielded views that were startling, and in some cases, overtly discriminatory:

• Doctors complained about the “burden” of caring for a patient with a disability.
• They lacked the time or equipment, such as accessible exam tables or weight scales.
• They admitted to inventing excuses for why appointments were not available or routine diagnostic tests were not performed.
• They described being fearful of lawsuits under the Americans with Disabilities Act.

The overall message was summed up in one doctor’s statement: “I am not the doctor for you.”

“Doctors are people too,” Dr. Iezzoni pointed out. “And so they reflect the same prejudices and stigmatized attitudes of the rest of the population. It might be implicit, so they might not be aware of it. [But] it might be explicit.”

Ableism in the medical field is all too familiar to Dr. Iezzoni. She was diagnosed with multiple sclerosis at age 26 during her first year at Harvard Medical School in the early 1980s. Despite symptom flare-ups, Dr. Iezzoni was able to graduate with her class, but many instructors and administrators had little interest in accommodating her physical limitations. In fact, several physicians discouraged her from continuing to train.

Unable to take call, run up flights of stairs, or stand for hours at a time, Dr. Iezzoni remembers being told by a senior surgeon that she shouldn’t become a doctor since she lacked the “most important quality,” which was “24/7 availability.” A hospital CEO informed her: “There are too many doctors in the country right now for us to worry about training a handicapped physician. If that means that some people get left by the wayside, so be it.”

Ultimately, Harvard Medical School declined to write Dr. Iezzoni a letter of recommendation for an internship. She would never practice medicine. “My career was just truncated from the start,” Dr. Iezzoni said. “It never happened because of discrimination.”

She later learned the legal term for her treatment: constructive dismissal.

“The medical school didn’t outright say, ‘Go away. We’re not allowing you to graduate.’ ” Dr. Iezzoni explained. “But they made my life so difficult that I did so voluntarily.”

Dr. Iezzoni graduated in 1984, before the passage of the ADA in 1990, and she refers to her experience as a “ghost from the past,” a historical reminder of how the legal landscape has changed – even though the tendency toward bias may not have.
 

The fight for inclusion

Zainub Dhanani, a fifth-year medical student at Stanford (Calif.) University, won’t forget an interview at one of the other schools to which she applied. The interviewer asked how she expected to be in a hospital all day if she had a chronic illness.

“Does it really make sense?” he wanted to know.

The question shocked her in the moment, but now she sees this type of bias as linked to the inequalities that many marginalized groups face in health care and beyond. That’s also why she believes physician-patients are crucial to improve the quality of care for people with chronic illness and other groups that face discrimination.

Who else, she wonders, could provide that “reaffirming” experience for patients or have that “unique edge” other than a provider who has navigated the same world?

Ms. Dhanani is the executive director and founder of Medical Students With Disability and Chronic Illness, an organization dedicated to empowering these students through advocacy, education, accessibility, and community. The group now has 19 chapters at medical schools across the country.

Ms. Dhanani said she has received excellent accommodations from Stanford for her own condition (which she prefers not to disclose), but all medical schools are not as responsive to students with various physical needs. Her organization offers support and resources to inform these future physicians about their options and rights.

“Disability justice is also racial justice,” Ms. Dhanani stressed. “It’s also environmental justice. It’s also gender and sexuality-based justice. Those compounded layers of biases lead to worse and worse levels of care. As a patient, it’s terrifying. And as a future physician, it’s tragic to know that this is something so pervasive and yet so under-addressed in medicine.”
 

Soldiering on

Unfortunately, for some physicians with chronic illness, there are no practical accommodations that could save their careers in clinical practice.

Dr. Stenehjem now works part-time as a health consultant, helping those with chronic illnesses navigate their health care systems.

Dr. Bluestein offers a similar coaching service to patients with Ehlers-Danlos syndrome (EDS) and other connective tissue and hypermobility disorders. Because of her own EDS, she can no longer practice as an anesthesiologist but instead opened an integrative pain management practice for patients with complex pain conditions..

She believes the idea that doctors are “invincible” needs to change. She recalls the time her former group practice told her in no uncertain terms to “never call in sick.”

The stories she hears from her current clients are similar to her own. She can empathize, knowing firsthand the physical and psychological damage these attitudes can cause.

“When I was at my worst physically, I was also at my worst psychologically,” said Dr. Bluestein. “We tend to think of them as separate, but they go hand in hand. If we can validate people’s experiences rather than disregard them, it has a positive forward cycle, as opposed to the reverse, which is what usually happens.”

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

Linda Bluestein remembers all the doctors who missed, ignored, or incompletely diagnosed her chronic illness.

There was the orthopedic surgeon who noted her hyperextended elbows but failed to check any of her other joints. The gastroenterologist who insisted on performing multiple scoping procedures but wouldn’t discuss how to manage her symptoms. The other surgeon who, after performing arthroscopy on her injured knee, yelled at her: “There is nothing wrong with your knee! You’re fine!” in a room full of people.

And then there was the rheumatologist who said: “Oh, you want something to be wrong with you?”

“No,” she replied, “I want an explanation. I want to keep working. I just want to know why these things keep happening to me.”

The medical frustration she experienced was especially difficult because, like her health care providers, Linda Bluestein has an MD after her name. She is a board-certified anesthesiologist and integrative medicine physician.

Living with a chronic illness is a challenge for any patient. But physicians who are diagnosed with chronic conditions face a unique set of personal and professional issues.

Along with the physically demanding schedule of medical practice, they must cope with what many call a “culture of invincibility” within medicine. Doctors are not supposed to get sick. In fact, the unwritten rule is presenteeism – to function without adequate food or sleep and to never prioritize their own self-care over their dedication to their patients.

Whether their conditions are visible, such as muscular dystrophy and multiple sclerosis, or invisible, such as fibromyalgia and mental illnesses – and now, long COVID – these doctors often meet significant stigma. They fight the assumption that they are less capable than their colleagues.

But they also experience an invaluable benefit: They gain firsthand knowledge of the patient experience, a profound understanding which, they say, enhances how they care for their own patients.
 

What it takes to become a doctor when you have a chronic condition

In short, it’s not easy.

Data from the 2018 National Health Interview Survey show that more than half of U.S. adults had at least one of several chronic conditions, including rheumatoid arthritis, asthma, diabetes, hypertension, and kidney problems. Nearly a third of respondents had more than one condition. But fewer than 5% of medical students and 3% of practicing physicians report having a chronic illness or disability, according to studies from 2019 and 2021.

While that could mean that fewer people with chronic illness enter medicine, cases also exist in which aspiring physicians with conditions were dissuaded from pursuing a career in medicine at all.

Amy Stenehjem, MD, a physical medicine and rehabilitation physician, is one of the exceptions. Diagnosed with several autoimmune-related conditions as a teenager and young adult, Dr. Stenehjem was determined to become a doctor. In her 20s, her health was relatively stable, and she was able to manage medical school and residency. Her training institutions agreed to provide some accommodations that helped her succeed.

“They let me build some flexibility into the training,” Dr. Stenehjem said. “In medical school, when I knew I wasn’t going to be able to do a particular specialty as a career, they let me work with an attending doctor that did not require a lot of on-call time during that particular rotation.”

Dr. Stenehjem specialized in chronic neck and back disorders, fibromyalgia, chronic fatigue syndrome (myalgic encephalomyelitis), and autoimmune-related diseases. She practiced for more than a decade. But in 2011, her condition spiraled. She couldn’t walk a few steps or even sit upright without experiencing dizziness and shortness of breath. She had debilitating fatigue and episodes of fever, rash, headaches, and joint pain.

It would take 7 years and more than 20 doctors to determine Dr. Stenehjem’s multiple diagnoses. In addition to her autoimmune diseases, she was diagnosed with postural orthostatic tachycardia syndrome, autoinflammatory periodic fever syndrome, Lyme disease, and reactivated Epstein-Barr infection.

While she suspects that her providers gave her more “leeway” because she was a physician, many did not show a deep understanding of the severity of her symptoms and the impact those symptoms had.

“When I was practicing, I really didn’t fully understand the impact chronic illness had on my patients,” Dr. Stenehjem said. “Things like chronic dizziness, headaches, fatigue, pain, or brain fog can be really hard to understand unless you’ve experienced these symptoms. When I got sick, I finally realized, ‘Oh my goodness, when a patient says they’re dealing with fatigue, this is not your normal, I’m-super-tired-from-being-on-call fatigue. This is I-can’t-get-out-of-bed fatigue.’ That’s what people with chronic illness often deal with on a daily basis.”
 

Treating the individual

Dr. Stenehjem was aware that her chronic illness would affect her medical career. For Jason Baker, MD, an endocrinologist at Weill Cornell Medicine, New York, it came as a shock. Dr. Baker was a third-year medical student when he experienced increased urination and rapid weight loss. It was only when friends pressed him to visit student health that a blood test revealed type 1 diabetes. Dr. Baker suddenly found himself lying in a hospital bed.

He remembers an attending physician who simply handed him a textbook on diabetic ketoacidosis (DKA) and a resident who informed him that he had kidney damage, which turned out to be untrue. Neither discussed the psychological issues from a frightening diagnosis that would require lifelong, daily management.

“There certainly could have been a bit more empathy from some of the people I dealt with early on,” he said.

Although his training gave him a stark picture of worst-case scenarios, Dr. Baker found that knowledge motivating. “I’d already seen patients come in who had diabetes complications,” Dr. Baker says. “I vowed to never ever get those complications. It was a good balance of fear and motivation.”

Dr. Baker had not planned to specialize in endocrinology, but he quickly realized that his personal diagnosis could help others. Now he often shares his experience with his patients who have diabetes, which he says makes them more comfortable discussing their own problems.

His approach, Dr. Baker explained, is to treat everyone as an individual. Trying to neatly classify patients with chronic illness is a common mistake he notices among physicians.

“There’s a lot of misunderstanding about type 1 versus type 2 [diabetes],” Dr. Baker said, “and trying to categorize people when sometimes people can’t be categorized. That’s really with any chronic condition; there’s no one size fits all.”

Managing his health is still a time-consuming task. At work, he needs breaks to eat, check his blood sugar, or take insulin. “During the workday seeing patients, I have to also remember that I’m a patient,” Dr. Baker said. “I have to be okay with prioritizing my own health. Otherwise I can’t help anybody.”
 

‘I am not the doctor for you’

Chronic diseases such as diabetes or hypertension are familiar to most doctors, and with good management, patients can usually function normally. When chronic conditions become disabling, however, attitudes in the medical field can change.

According to data from the Centers for Disease Control and Prevention and from studies, people with disabilities experience significant disparities and barriers to care. Some of this can be linked to social determinants of health. People with disabilities are more likely to be poor and to rely on Medicare and Medicaid for insurance coverage. But lack of training, unwillingness to provide accommodations, ignorance of legal requirements, and inaccurate assumptions among physicians also play a role.

These are themes that Lisa Iezzoni, MD, a professor of medicine at Harvard Medical School, Boston, has heard from hundreds of patients with disabilities during the more than 25 years that she has conducted research.

In late 2019, Dr. Iezzoni and coinvestigators fielded a national survey of 714 practicing physicians. Only 40.7% reported they were “very confident” that they could provide the same quality of care to patients with disabilities as they do for other patients. And only 56.5% “strongly agreed” that they welcomed these patients into their practices.

The survey was conducted through a series of small focus groups that Dr. Iezzoni held with physicians in 2018. These yielded views that were startling, and in some cases, overtly discriminatory:

• Doctors complained about the “burden” of caring for a patient with a disability.
• They lacked the time or equipment, such as accessible exam tables or weight scales.
• They admitted to inventing excuses for why appointments were not available or routine diagnostic tests were not performed.
• They described being fearful of lawsuits under the Americans with Disabilities Act.

The overall message was summed up in one doctor’s statement: “I am not the doctor for you.”

“Doctors are people too,” Dr. Iezzoni pointed out. “And so they reflect the same prejudices and stigmatized attitudes of the rest of the population. It might be implicit, so they might not be aware of it. [But] it might be explicit.”

Ableism in the medical field is all too familiar to Dr. Iezzoni. She was diagnosed with multiple sclerosis at age 26 during her first year at Harvard Medical School in the early 1980s. Despite symptom flare-ups, Dr. Iezzoni was able to graduate with her class, but many instructors and administrators had little interest in accommodating her physical limitations. In fact, several physicians discouraged her from continuing to train.

Unable to take call, run up flights of stairs, or stand for hours at a time, Dr. Iezzoni remembers being told by a senior surgeon that she shouldn’t become a doctor since she lacked the “most important quality,” which was “24/7 availability.” A hospital CEO informed her: “There are too many doctors in the country right now for us to worry about training a handicapped physician. If that means that some people get left by the wayside, so be it.”

Ultimately, Harvard Medical School declined to write Dr. Iezzoni a letter of recommendation for an internship. She would never practice medicine. “My career was just truncated from the start,” Dr. Iezzoni said. “It never happened because of discrimination.”

She later learned the legal term for her treatment: constructive dismissal.

“The medical school didn’t outright say, ‘Go away. We’re not allowing you to graduate.’ ” Dr. Iezzoni explained. “But they made my life so difficult that I did so voluntarily.”

Dr. Iezzoni graduated in 1984, before the passage of the ADA in 1990, and she refers to her experience as a “ghost from the past,” a historical reminder of how the legal landscape has changed – even though the tendency toward bias may not have.
 

The fight for inclusion

Zainub Dhanani, a fifth-year medical student at Stanford (Calif.) University, won’t forget an interview at one of the other schools to which she applied. The interviewer asked how she expected to be in a hospital all day if she had a chronic illness.

“Does it really make sense?” he wanted to know.

The question shocked her in the moment, but now she sees this type of bias as linked to the inequalities that many marginalized groups face in health care and beyond. That’s also why she believes physician-patients are crucial to improve the quality of care for people with chronic illness and other groups that face discrimination.

Who else, she wonders, could provide that “reaffirming” experience for patients or have that “unique edge” other than a provider who has navigated the same world?

Ms. Dhanani is the executive director and founder of Medical Students With Disability and Chronic Illness, an organization dedicated to empowering these students through advocacy, education, accessibility, and community. The group now has 19 chapters at medical schools across the country.

Ms. Dhanani said she has received excellent accommodations from Stanford for her own condition (which she prefers not to disclose), but all medical schools are not as responsive to students with various physical needs. Her organization offers support and resources to inform these future physicians about their options and rights.

“Disability justice is also racial justice,” Ms. Dhanani stressed. “It’s also environmental justice. It’s also gender and sexuality-based justice. Those compounded layers of biases lead to worse and worse levels of care. As a patient, it’s terrifying. And as a future physician, it’s tragic to know that this is something so pervasive and yet so under-addressed in medicine.”
 

Soldiering on

Unfortunately, for some physicians with chronic illness, there are no practical accommodations that could save their careers in clinical practice.

Dr. Stenehjem now works part-time as a health consultant, helping those with chronic illnesses navigate their health care systems.

Dr. Bluestein offers a similar coaching service to patients with Ehlers-Danlos syndrome (EDS) and other connective tissue and hypermobility disorders. Because of her own EDS, she can no longer practice as an anesthesiologist but instead opened an integrative pain management practice for patients with complex pain conditions..

She believes the idea that doctors are “invincible” needs to change. She recalls the time her former group practice told her in no uncertain terms to “never call in sick.”

The stories she hears from her current clients are similar to her own. She can empathize, knowing firsthand the physical and psychological damage these attitudes can cause.

“When I was at my worst physically, I was also at my worst psychologically,” said Dr. Bluestein. “We tend to think of them as separate, but they go hand in hand. If we can validate people’s experiences rather than disregard them, it has a positive forward cycle, as opposed to the reverse, which is what usually happens.”

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

Linda Bluestein remembers all the doctors who missed, ignored, or incompletely diagnosed her chronic illness.

There was the orthopedic surgeon who noted her hyperextended elbows but failed to check any of her other joints. The gastroenterologist who insisted on performing multiple scoping procedures but wouldn’t discuss how to manage her symptoms. The other surgeon who, after performing arthroscopy on her injured knee, yelled at her: “There is nothing wrong with your knee! You’re fine!” in a room full of people.

And then there was the rheumatologist who said: “Oh, you want something to be wrong with you?”

“No,” she replied, “I want an explanation. I want to keep working. I just want to know why these things keep happening to me.”

The medical frustration she experienced was especially difficult because, like her health care providers, Linda Bluestein has an MD after her name. She is a board-certified anesthesiologist and integrative medicine physician.

Living with a chronic illness is a challenge for any patient. But physicians who are diagnosed with chronic conditions face a unique set of personal and professional issues.

Along with the physically demanding schedule of medical practice, they must cope with what many call a “culture of invincibility” within medicine. Doctors are not supposed to get sick. In fact, the unwritten rule is presenteeism – to function without adequate food or sleep and to never prioritize their own self-care over their dedication to their patients.

Whether their conditions are visible, such as muscular dystrophy and multiple sclerosis, or invisible, such as fibromyalgia and mental illnesses – and now, long COVID – these doctors often meet significant stigma. They fight the assumption that they are less capable than their colleagues.

But they also experience an invaluable benefit: They gain firsthand knowledge of the patient experience, a profound understanding which, they say, enhances how they care for their own patients.
 

What it takes to become a doctor when you have a chronic condition

In short, it’s not easy.

Data from the 2018 National Health Interview Survey show that more than half of U.S. adults had at least one of several chronic conditions, including rheumatoid arthritis, asthma, diabetes, hypertension, and kidney problems. Nearly a third of respondents had more than one condition. But fewer than 5% of medical students and 3% of practicing physicians report having a chronic illness or disability, according to studies from 2019 and 2021.

While that could mean that fewer people with chronic illness enter medicine, cases also exist in which aspiring physicians with conditions were dissuaded from pursuing a career in medicine at all.

Amy Stenehjem, MD, a physical medicine and rehabilitation physician, is one of the exceptions. Diagnosed with several autoimmune-related conditions as a teenager and young adult, Dr. Stenehjem was determined to become a doctor. In her 20s, her health was relatively stable, and she was able to manage medical school and residency. Her training institutions agreed to provide some accommodations that helped her succeed.

“They let me build some flexibility into the training,” Dr. Stenehjem said. “In medical school, when I knew I wasn’t going to be able to do a particular specialty as a career, they let me work with an attending doctor that did not require a lot of on-call time during that particular rotation.”

Dr. Stenehjem specialized in chronic neck and back disorders, fibromyalgia, chronic fatigue syndrome (myalgic encephalomyelitis), and autoimmune-related diseases. She practiced for more than a decade. But in 2011, her condition spiraled. She couldn’t walk a few steps or even sit upright without experiencing dizziness and shortness of breath. She had debilitating fatigue and episodes of fever, rash, headaches, and joint pain.

It would take 7 years and more than 20 doctors to determine Dr. Stenehjem’s multiple diagnoses. In addition to her autoimmune diseases, she was diagnosed with postural orthostatic tachycardia syndrome, autoinflammatory periodic fever syndrome, Lyme disease, and reactivated Epstein-Barr infection.

While she suspects that her providers gave her more “leeway” because she was a physician, many did not show a deep understanding of the severity of her symptoms and the impact those symptoms had.

“When I was practicing, I really didn’t fully understand the impact chronic illness had on my patients,” Dr. Stenehjem said. “Things like chronic dizziness, headaches, fatigue, pain, or brain fog can be really hard to understand unless you’ve experienced these symptoms. When I got sick, I finally realized, ‘Oh my goodness, when a patient says they’re dealing with fatigue, this is not your normal, I’m-super-tired-from-being-on-call fatigue. This is I-can’t-get-out-of-bed fatigue.’ That’s what people with chronic illness often deal with on a daily basis.”
 

Treating the individual

Dr. Stenehjem was aware that her chronic illness would affect her medical career. For Jason Baker, MD, an endocrinologist at Weill Cornell Medicine, New York, it came as a shock. Dr. Baker was a third-year medical student when he experienced increased urination and rapid weight loss. It was only when friends pressed him to visit student health that a blood test revealed type 1 diabetes. Dr. Baker suddenly found himself lying in a hospital bed.

He remembers an attending physician who simply handed him a textbook on diabetic ketoacidosis (DKA) and a resident who informed him that he had kidney damage, which turned out to be untrue. Neither discussed the psychological issues from a frightening diagnosis that would require lifelong, daily management.

“There certainly could have been a bit more empathy from some of the people I dealt with early on,” he said.

Although his training gave him a stark picture of worst-case scenarios, Dr. Baker found that knowledge motivating. “I’d already seen patients come in who had diabetes complications,” Dr. Baker says. “I vowed to never ever get those complications. It was a good balance of fear and motivation.”

Dr. Baker had not planned to specialize in endocrinology, but he quickly realized that his personal diagnosis could help others. Now he often shares his experience with his patients who have diabetes, which he says makes them more comfortable discussing their own problems.

His approach, Dr. Baker explained, is to treat everyone as an individual. Trying to neatly classify patients with chronic illness is a common mistake he notices among physicians.

“There’s a lot of misunderstanding about type 1 versus type 2 [diabetes],” Dr. Baker said, “and trying to categorize people when sometimes people can’t be categorized. That’s really with any chronic condition; there’s no one size fits all.”

Managing his health is still a time-consuming task. At work, he needs breaks to eat, check his blood sugar, or take insulin. “During the workday seeing patients, I have to also remember that I’m a patient,” Dr. Baker said. “I have to be okay with prioritizing my own health. Otherwise I can’t help anybody.”
 

‘I am not the doctor for you’

Chronic diseases such as diabetes or hypertension are familiar to most doctors, and with good management, patients can usually function normally. When chronic conditions become disabling, however, attitudes in the medical field can change.

According to data from the Centers for Disease Control and Prevention and from studies, people with disabilities experience significant disparities and barriers to care. Some of this can be linked to social determinants of health. People with disabilities are more likely to be poor and to rely on Medicare and Medicaid for insurance coverage. But lack of training, unwillingness to provide accommodations, ignorance of legal requirements, and inaccurate assumptions among physicians also play a role.

These are themes that Lisa Iezzoni, MD, a professor of medicine at Harvard Medical School, Boston, has heard from hundreds of patients with disabilities during the more than 25 years that she has conducted research.

In late 2019, Dr. Iezzoni and coinvestigators fielded a national survey of 714 practicing physicians. Only 40.7% reported they were “very confident” that they could provide the same quality of care to patients with disabilities as they do for other patients. And only 56.5% “strongly agreed” that they welcomed these patients into their practices.

The survey was conducted through a series of small focus groups that Dr. Iezzoni held with physicians in 2018. These yielded views that were startling, and in some cases, overtly discriminatory:

• Doctors complained about the “burden” of caring for a patient with a disability.
• They lacked the time or equipment, such as accessible exam tables or weight scales.
• They admitted to inventing excuses for why appointments were not available or routine diagnostic tests were not performed.
• They described being fearful of lawsuits under the Americans with Disabilities Act.

The overall message was summed up in one doctor’s statement: “I am not the doctor for you.”

“Doctors are people too,” Dr. Iezzoni pointed out. “And so they reflect the same prejudices and stigmatized attitudes of the rest of the population. It might be implicit, so they might not be aware of it. [But] it might be explicit.”

Ableism in the medical field is all too familiar to Dr. Iezzoni. She was diagnosed with multiple sclerosis at age 26 during her first year at Harvard Medical School in the early 1980s. Despite symptom flare-ups, Dr. Iezzoni was able to graduate with her class, but many instructors and administrators had little interest in accommodating her physical limitations. In fact, several physicians discouraged her from continuing to train.

Unable to take call, run up flights of stairs, or stand for hours at a time, Dr. Iezzoni remembers being told by a senior surgeon that she shouldn’t become a doctor since she lacked the “most important quality,” which was “24/7 availability.” A hospital CEO informed her: “There are too many doctors in the country right now for us to worry about training a handicapped physician. If that means that some people get left by the wayside, so be it.”

Ultimately, Harvard Medical School declined to write Dr. Iezzoni a letter of recommendation for an internship. She would never practice medicine. “My career was just truncated from the start,” Dr. Iezzoni said. “It never happened because of discrimination.”

She later learned the legal term for her treatment: constructive dismissal.

“The medical school didn’t outright say, ‘Go away. We’re not allowing you to graduate.’ ” Dr. Iezzoni explained. “But they made my life so difficult that I did so voluntarily.”

Dr. Iezzoni graduated in 1984, before the passage of the ADA in 1990, and she refers to her experience as a “ghost from the past,” a historical reminder of how the legal landscape has changed – even though the tendency toward bias may not have.
 

The fight for inclusion

Zainub Dhanani, a fifth-year medical student at Stanford (Calif.) University, won’t forget an interview at one of the other schools to which she applied. The interviewer asked how she expected to be in a hospital all day if she had a chronic illness.

“Does it really make sense?” he wanted to know.

The question shocked her in the moment, but now she sees this type of bias as linked to the inequalities that many marginalized groups face in health care and beyond. That’s also why she believes physician-patients are crucial to improve the quality of care for people with chronic illness and other groups that face discrimination.

Who else, she wonders, could provide that “reaffirming” experience for patients or have that “unique edge” other than a provider who has navigated the same world?

Ms. Dhanani is the executive director and founder of Medical Students With Disability and Chronic Illness, an organization dedicated to empowering these students through advocacy, education, accessibility, and community. The group now has 19 chapters at medical schools across the country.

Ms. Dhanani said she has received excellent accommodations from Stanford for her own condition (which she prefers not to disclose), but all medical schools are not as responsive to students with various physical needs. Her organization offers support and resources to inform these future physicians about their options and rights.

“Disability justice is also racial justice,” Ms. Dhanani stressed. “It’s also environmental justice. It’s also gender and sexuality-based justice. Those compounded layers of biases lead to worse and worse levels of care. As a patient, it’s terrifying. And as a future physician, it’s tragic to know that this is something so pervasive and yet so under-addressed in medicine.”
 

Soldiering on

Unfortunately, for some physicians with chronic illness, there are no practical accommodations that could save their careers in clinical practice.

Dr. Stenehjem now works part-time as a health consultant, helping those with chronic illnesses navigate their health care systems.

Dr. Bluestein offers a similar coaching service to patients with Ehlers-Danlos syndrome (EDS) and other connective tissue and hypermobility disorders. Because of her own EDS, she can no longer practice as an anesthesiologist but instead opened an integrative pain management practice for patients with complex pain conditions..

She believes the idea that doctors are “invincible” needs to change. She recalls the time her former group practice told her in no uncertain terms to “never call in sick.”

The stories she hears from her current clients are similar to her own. She can empathize, knowing firsthand the physical and psychological damage these attitudes can cause.

“When I was at my worst physically, I was also at my worst psychologically,” said Dr. Bluestein. “We tend to think of them as separate, but they go hand in hand. If we can validate people’s experiences rather than disregard them, it has a positive forward cycle, as opposed to the reverse, which is what usually happens.”

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

My use of drug names is a mixed bag of terms.

In medical school we learn drugs by their generic names, but it doesn’t take long before we realize that each has both a generic name and one (or more) brand names. I suppose there’s also the chemical names, but no one outside the lab uses those. They’re waaaaay too long.

There is, for better or worse, a lot of variability in this. The purists (almost always academics, or cardiologists, or academic cardiologists) insist on generic names only. In their notes, conversations, presentations, whatever. If you’re a medical student or resident under them, you learn fast not to use the brand name.

After 30 years of doing this ... I don’t care. My notes are a mishmash of both.

Let’s face it, brand names are generally shorter and easier to type, spell, and pronounce than the generic names. I still need to know both, but when I’m writing up a note Keppra is far easier than levetiracetam. And most patients find the brand names a lot easier to say and remember.

An even weirder point, which is my own, is that one of my teaching attendings insisted that we capitalize both generic and brand names while on his rotation. Why? He never explained that, but he was pretty insistent. Now, for whatever reason, the habit has stuck with me. I’m sure the cardiologist down the hall would love to send my notes back, heavily marked up with red ink.

There’s even a weird subdivisions in this: Aspirin is a brand name by Bayer. Shouldn’t it be capitalized in our notes? But it isn’t, and to make things more confusing that varies by country. Why? (if you’re curious, it’s a strange combination of 100-year-old patent claims, generic trademark rulings, and also what country you’re in, whether it was involved in World War I, and, if so, which side. Really).

So the medical lists in my notes are certainly understandable, though aren’t going to score me any points for academic correctness. Not that I care. As a medical Shakespeare might have written, Imitrex, Onzetra, Zembrace, Tosymra, Sumavel, Alsuma, Imigran, Migraitan, and Zecuity ... are still sumatriptan by any other name.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

My use of drug names is a mixed bag of terms.

In medical school we learn drugs by their generic names, but it doesn’t take long before we realize that each has both a generic name and one (or more) brand names. I suppose there’s also the chemical names, but no one outside the lab uses those. They’re waaaaay too long.

There is, for better or worse, a lot of variability in this. The purists (almost always academics, or cardiologists, or academic cardiologists) insist on generic names only. In their notes, conversations, presentations, whatever. If you’re a medical student or resident under them, you learn fast not to use the brand name.

After 30 years of doing this ... I don’t care. My notes are a mishmash of both.

Let’s face it, brand names are generally shorter and easier to type, spell, and pronounce than the generic names. I still need to know both, but when I’m writing up a note Keppra is far easier than levetiracetam. And most patients find the brand names a lot easier to say and remember.

An even weirder point, which is my own, is that one of my teaching attendings insisted that we capitalize both generic and brand names while on his rotation. Why? He never explained that, but he was pretty insistent. Now, for whatever reason, the habit has stuck with me. I’m sure the cardiologist down the hall would love to send my notes back, heavily marked up with red ink.

There’s even a weird subdivisions in this: Aspirin is a brand name by Bayer. Shouldn’t it be capitalized in our notes? But it isn’t, and to make things more confusing that varies by country. Why? (if you’re curious, it’s a strange combination of 100-year-old patent claims, generic trademark rulings, and also what country you’re in, whether it was involved in World War I, and, if so, which side. Really).

So the medical lists in my notes are certainly understandable, though aren’t going to score me any points for academic correctness. Not that I care. As a medical Shakespeare might have written, Imitrex, Onzetra, Zembrace, Tosymra, Sumavel, Alsuma, Imigran, Migraitan, and Zecuity ... are still sumatriptan by any other name.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

My use of drug names is a mixed bag of terms.

In medical school we learn drugs by their generic names, but it doesn’t take long before we realize that each has both a generic name and one (or more) brand names. I suppose there’s also the chemical names, but no one outside the lab uses those. They’re waaaaay too long.

There is, for better or worse, a lot of variability in this. The purists (almost always academics, or cardiologists, or academic cardiologists) insist on generic names only. In their notes, conversations, presentations, whatever. If you’re a medical student or resident under them, you learn fast not to use the brand name.

After 30 years of doing this ... I don’t care. My notes are a mishmash of both.

Let’s face it, brand names are generally shorter and easier to type, spell, and pronounce than the generic names. I still need to know both, but when I’m writing up a note Keppra is far easier than levetiracetam. And most patients find the brand names a lot easier to say and remember.

An even weirder point, which is my own, is that one of my teaching attendings insisted that we capitalize both generic and brand names while on his rotation. Why? He never explained that, but he was pretty insistent. Now, for whatever reason, the habit has stuck with me. I’m sure the cardiologist down the hall would love to send my notes back, heavily marked up with red ink.

There’s even a weird subdivisions in this: Aspirin is a brand name by Bayer. Shouldn’t it be capitalized in our notes? But it isn’t, and to make things more confusing that varies by country. Why? (if you’re curious, it’s a strange combination of 100-year-old patent claims, generic trademark rulings, and also what country you’re in, whether it was involved in World War I, and, if so, which side. Really).

So the medical lists in my notes are certainly understandable, though aren’t going to score me any points for academic correctness. Not that I care. As a medical Shakespeare might have written, Imitrex, Onzetra, Zembrace, Tosymra, Sumavel, Alsuma, Imigran, Migraitan, and Zecuity ... are still sumatriptan by any other name.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

DENVER – The use of mindfulness-based interventions for patients with multiple sclerosis (MS), whether delivered in person or through online video conferencing, resulted in improved cognitive function and reduced symptoms of depression, anxiety, and stress, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Two studies assessed the effects of two mindfulness-based stress reduction (MBSR) programs, one primarily in person until the pandemic forced a move to online participation, and the other exclusively online. The in-person course also found, in a subset of the participants, that blood inflammation markers matched the patients’ reported reduction in stress and loneliness.
 

Putting mindfulness to the test

Previous research has found that life stressors are linked to clinical MS flares, Chris Hemond, MD, an assistant professor of neurology at the University of Massachusetts, Worcester, told attendees. He also noted previous research exploring possible explanations for how MBSR programs might improve clinical symptoms of MS. One hypothesis involves an effect on the “forebrain limbic areas responsible for the neurobiological stress response.” Part of this study therefore involved looking for possible MRI changes before and after the MBSR program to test this hypothesis.

The study involved 23 patients, all women with relapsing remitting MS with an median age of 45, and 57% of whom were taking B cell–depleting agents. The patients’ average Expanded Disability Status Scale score was 2, and none experienced any new clinical or MRI disease activity during a 12-week observation period.

Patients volunteered to participate in the free 8-week MBSR program. Half attended MBSR classes in person while the other half had to attend virtual classes due to the pandemic. The program involved eight weekly 2.5-hour classes with daily homework assignments. The program, developed by Jon Kabat-Zinn at the University of Massachusetts, is intended to be “mental training for nonjudgmental awareness of moment-to-moment experience” that aims to “improve accuracy of perception, acceptance of intractable health-related changes, realistic sense of control, and appreciation of available life experiences,” Dr. Hemond said.

Among the 91% of participants who completed the course, 57% underwent both pre- and postcourse structural MRI scans, and 83% completed both the pre- and postcourse questionnaires. A subset of patients (53%) also provided blood samples for analysis of inflammatory gene expression markers.

“The conserved transcriptional response to adversity (CTRA) score was determined using well-established methods from 53 prespecified blood gene expression markers representing a composite of inflammation, interferon response, and immunoglobulin expression,” Dr. Hemond explained.

Participants’ average scores both pre- and post questionnaires revealed statistically significant improvements in stress, anxiety, depression, fatigue, loneliness, well-being, and interoceptive awareness (P < .01 for all).

Although precise values were not provided in the presentation, patients’ scores significantly decreased on the Brief Inventory of Perceived Stress (BIPS) for “lack of control,” “pushed,” and “conflict” (P < .03). Average scores also improved (decreased) on the Modified Fatigue Inventory Scale, the UCLA Loneliness Scale, and all three subscales of the Depression Anxiety Stress Scales assessment (P <.01). Participants’ scores increased on the Mental Health Continuum “hedonic” and “eudaimonic well-being” scales (P < .05).

Improvements on the Multidimensional Assessment of Interoceptive Awareness included self-regulation, attention regulation, “noticing” (P = .02), “not worrying” (P < .01), “emotional awareness” (P < .01), “body listening” (P < .01), and “trusting” (P < .01).

After adjustment for age, race, body mass index, medical therapy and time, the researchers found changes in inflammatory gene expression in the 12 participants who provided blood samples, and these changes correlated inversely with changes in their reported loneliness (P =.002), pain (P <.001), several interoception aspects (P < .01), and stress (P < .0001), particularly regarding feeling a lack of control.

Although no structural MRI changes were observed in the amygdala or prefrontal cortex, the researchers did see a 1% volume increase on the right-side hippocampus. Though the increase was significant (P < .01) and right hippocampal enlargement has been linked with MBSR in past studies, Dr. Hemond acknowledged the study’s small sample size and urged caution in interpreting that finding.

Dr. Hemond also reported that interaction between higher CTRA and the MSBR training attenuated the right hippocampal volume increase that was seen with MBSR, a finding which raises more questions than it answers.

The primary finding, however, was that “mindfulness-based stress reduction was associated with substantial improvement in multiple patient-reported outcomes of the debilitating ‘silent symptoms’ of MS,” Dr. Hemond told attendees. Though the study is limited by its small sample size, observational biases, and missing data, the findings suggest the possibility that MBSR is also associated with structural limbic brain changes, especially in the right hippocampus.
 

Another tool for managing MS

Ellen Mowry, MD, MCR, a professor of neurology and epidemiology at Johns Hopkins University, Baltimore, who attended the presentation, said she was very enthusiastic about this research.

“People with MS often are seeking ways that they can have self-efficacy and managing the symptoms of their disease, and we know that the disease-modifying therapies make a big difference, but we need additional therapies that can help people feel better and live better with MS,” Dr. Mowry commented.

She also acknowledged the challenges, however, in developing a mindfulness program that is accessible by a broad range of MS patients. This particular program involved several hours of work per day.

“People with MS often are either on the younger side, and they’re working and raising their family and doing all the same stuff that everybody else is doing, or they might be quite disabled and have more fatigue and other things that might make it really challenging to persist through that long of an intervention,” Dr. Mowry said.

The ideal program would be one that’s financially accessible, either through insurance, society more broadly, or another source, and which is logistically feasible for a wide range of patients. Finding a “sweet spot” with a program that doesn’t “require such a lengthy amount of time in order to see a success would be really great,” Dr. Mowry said. “You have to start somewhere, though, and you have to start with a program that’s already been tried and true and work from there.”
 

An online-only mindfulness program

One possible way to find that sweet spot is through an all-online program that patients access from home, similar to the 8-week MBSR program offered by Concord (N.H.) Hospital featured in the second study. The program was conducted via Zoom during once weekly synchronous meetings throughout 2021 and 2022 for eight cohorts of 5-15 participants each. The time of day the program was offered alternated between evening and daytime courses each quarter and was free for patients because of a hospital grant, according to Nicole Delcourt, BSN, RN, MSCN, of Concord Hospital Neurology, who facilitated patient sign-ups for the program.

Before and after each 8-week course, participants completed the PHQ-9, the PROMIS Cognitive Function, the PROMIS Fatigue–MS, and the Wasson Health Confidence assessments. Among the total 77 participating adults with MS, the completion rate was 81%, with 73% completing the preprogram assessments and 53% completed the postprogram assessments.

The assessments revealed a statistically significant increase in cognitive function and health confidence and decrease in depressive symptoms and fatigue following the program. Participants’ average PROMIS Cognitive Function scores increased from 16.7 before the program to 22.4 after, and their average Wasson Health Confidence score increased from 13.6 to 15.3 (P < .01 for both). Meanwhile, improvement in depressive symptoms was seen in participants’ decrease in Patient Health Questionnaire–9 scores from an average 6.9 to 4.6 (P = .01), and their average PROMIS Fatigue scores fell slightly but significantly from 59.3 to 55.3 (P < .05).

The participants “really felt like they were more in touch with their own feelings and emotions, and it helped them self-regulate,” Ms. Delcourt sad, “so it was really exciting.”

Patients also expressed satisfaction more subjectively in their feedback surveys. “I feel more aware of my body’s reactions to food and movement, and things that make me feel better physically,” one participant said. Another said that the class’s “lasting value ... will be to remember my own needs and how to become one with them.” Another participant praised the relevance of the printed and course materials, the speed of feedback on homework, and the quality of the video conference.

Dr. Hemond owns stock in VIVIO health. No other authors of either study reported other disclosures. Dr. Mowry has received grant funding from Biogen and Genentech. Ms. Delcourt had no disclosures. The in-person program study was funded by CMSC. Funding information for the Concord online program was unavailable.

DENVER – The use of mindfulness-based interventions for patients with multiple sclerosis (MS), whether delivered in person or through online video conferencing, resulted in improved cognitive function and reduced symptoms of depression, anxiety, and stress, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Two studies assessed the effects of two mindfulness-based stress reduction (MBSR) programs, one primarily in person until the pandemic forced a move to online participation, and the other exclusively online. The in-person course also found, in a subset of the participants, that blood inflammation markers matched the patients’ reported reduction in stress and loneliness.
 

Putting mindfulness to the test

Previous research has found that life stressors are linked to clinical MS flares, Chris Hemond, MD, an assistant professor of neurology at the University of Massachusetts, Worcester, told attendees. He also noted previous research exploring possible explanations for how MBSR programs might improve clinical symptoms of MS. One hypothesis involves an effect on the “forebrain limbic areas responsible for the neurobiological stress response.” Part of this study therefore involved looking for possible MRI changes before and after the MBSR program to test this hypothesis.

The study involved 23 patients, all women with relapsing remitting MS with an median age of 45, and 57% of whom were taking B cell–depleting agents. The patients’ average Expanded Disability Status Scale score was 2, and none experienced any new clinical or MRI disease activity during a 12-week observation period.

Patients volunteered to participate in the free 8-week MBSR program. Half attended MBSR classes in person while the other half had to attend virtual classes due to the pandemic. The program involved eight weekly 2.5-hour classes with daily homework assignments. The program, developed by Jon Kabat-Zinn at the University of Massachusetts, is intended to be “mental training for nonjudgmental awareness of moment-to-moment experience” that aims to “improve accuracy of perception, acceptance of intractable health-related changes, realistic sense of control, and appreciation of available life experiences,” Dr. Hemond said.

Among the 91% of participants who completed the course, 57% underwent both pre- and postcourse structural MRI scans, and 83% completed both the pre- and postcourse questionnaires. A subset of patients (53%) also provided blood samples for analysis of inflammatory gene expression markers.

“The conserved transcriptional response to adversity (CTRA) score was determined using well-established methods from 53 prespecified blood gene expression markers representing a composite of inflammation, interferon response, and immunoglobulin expression,” Dr. Hemond explained.

Participants’ average scores both pre- and post questionnaires revealed statistically significant improvements in stress, anxiety, depression, fatigue, loneliness, well-being, and interoceptive awareness (P < .01 for all).

Although precise values were not provided in the presentation, patients’ scores significantly decreased on the Brief Inventory of Perceived Stress (BIPS) for “lack of control,” “pushed,” and “conflict” (P < .03). Average scores also improved (decreased) on the Modified Fatigue Inventory Scale, the UCLA Loneliness Scale, and all three subscales of the Depression Anxiety Stress Scales assessment (P <.01). Participants’ scores increased on the Mental Health Continuum “hedonic” and “eudaimonic well-being” scales (P < .05).

Improvements on the Multidimensional Assessment of Interoceptive Awareness included self-regulation, attention regulation, “noticing” (P = .02), “not worrying” (P < .01), “emotional awareness” (P < .01), “body listening” (P < .01), and “trusting” (P < .01).

After adjustment for age, race, body mass index, medical therapy and time, the researchers found changes in inflammatory gene expression in the 12 participants who provided blood samples, and these changes correlated inversely with changes in their reported loneliness (P =.002), pain (P <.001), several interoception aspects (P < .01), and stress (P < .0001), particularly regarding feeling a lack of control.

Although no structural MRI changes were observed in the amygdala or prefrontal cortex, the researchers did see a 1% volume increase on the right-side hippocampus. Though the increase was significant (P < .01) and right hippocampal enlargement has been linked with MBSR in past studies, Dr. Hemond acknowledged the study’s small sample size and urged caution in interpreting that finding.

Dr. Hemond also reported that interaction between higher CTRA and the MSBR training attenuated the right hippocampal volume increase that was seen with MBSR, a finding which raises more questions than it answers.

The primary finding, however, was that “mindfulness-based stress reduction was associated with substantial improvement in multiple patient-reported outcomes of the debilitating ‘silent symptoms’ of MS,” Dr. Hemond told attendees. Though the study is limited by its small sample size, observational biases, and missing data, the findings suggest the possibility that MBSR is also associated with structural limbic brain changes, especially in the right hippocampus.
 

Another tool for managing MS

Ellen Mowry, MD, MCR, a professor of neurology and epidemiology at Johns Hopkins University, Baltimore, who attended the presentation, said she was very enthusiastic about this research.

“People with MS often are seeking ways that they can have self-efficacy and managing the symptoms of their disease, and we know that the disease-modifying therapies make a big difference, but we need additional therapies that can help people feel better and live better with MS,” Dr. Mowry commented.

She also acknowledged the challenges, however, in developing a mindfulness program that is accessible by a broad range of MS patients. This particular program involved several hours of work per day.

“People with MS often are either on the younger side, and they’re working and raising their family and doing all the same stuff that everybody else is doing, or they might be quite disabled and have more fatigue and other things that might make it really challenging to persist through that long of an intervention,” Dr. Mowry said.

The ideal program would be one that’s financially accessible, either through insurance, society more broadly, or another source, and which is logistically feasible for a wide range of patients. Finding a “sweet spot” with a program that doesn’t “require such a lengthy amount of time in order to see a success would be really great,” Dr. Mowry said. “You have to start somewhere, though, and you have to start with a program that’s already been tried and true and work from there.”
 

An online-only mindfulness program

One possible way to find that sweet spot is through an all-online program that patients access from home, similar to the 8-week MBSR program offered by Concord (N.H.) Hospital featured in the second study. The program was conducted via Zoom during once weekly synchronous meetings throughout 2021 and 2022 for eight cohorts of 5-15 participants each. The time of day the program was offered alternated between evening and daytime courses each quarter and was free for patients because of a hospital grant, according to Nicole Delcourt, BSN, RN, MSCN, of Concord Hospital Neurology, who facilitated patient sign-ups for the program.

Before and after each 8-week course, participants completed the PHQ-9, the PROMIS Cognitive Function, the PROMIS Fatigue–MS, and the Wasson Health Confidence assessments. Among the total 77 participating adults with MS, the completion rate was 81%, with 73% completing the preprogram assessments and 53% completed the postprogram assessments.

The assessments revealed a statistically significant increase in cognitive function and health confidence and decrease in depressive symptoms and fatigue following the program. Participants’ average PROMIS Cognitive Function scores increased from 16.7 before the program to 22.4 after, and their average Wasson Health Confidence score increased from 13.6 to 15.3 (P < .01 for both). Meanwhile, improvement in depressive symptoms was seen in participants’ decrease in Patient Health Questionnaire–9 scores from an average 6.9 to 4.6 (P = .01), and their average PROMIS Fatigue scores fell slightly but significantly from 59.3 to 55.3 (P < .05).

The participants “really felt like they were more in touch with their own feelings and emotions, and it helped them self-regulate,” Ms. Delcourt sad, “so it was really exciting.”

Patients also expressed satisfaction more subjectively in their feedback surveys. “I feel more aware of my body’s reactions to food and movement, and things that make me feel better physically,” one participant said. Another said that the class’s “lasting value ... will be to remember my own needs and how to become one with them.” Another participant praised the relevance of the printed and course materials, the speed of feedback on homework, and the quality of the video conference.

Dr. Hemond owns stock in VIVIO health. No other authors of either study reported other disclosures. Dr. Mowry has received grant funding from Biogen and Genentech. Ms. Delcourt had no disclosures. The in-person program study was funded by CMSC. Funding information for the Concord online program was unavailable.

DENVER – The use of mindfulness-based interventions for patients with multiple sclerosis (MS), whether delivered in person or through online video conferencing, resulted in improved cognitive function and reduced symptoms of depression, anxiety, and stress, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Two studies assessed the effects of two mindfulness-based stress reduction (MBSR) programs, one primarily in person until the pandemic forced a move to online participation, and the other exclusively online. The in-person course also found, in a subset of the participants, that blood inflammation markers matched the patients’ reported reduction in stress and loneliness.
 

Putting mindfulness to the test

Previous research has found that life stressors are linked to clinical MS flares, Chris Hemond, MD, an assistant professor of neurology at the University of Massachusetts, Worcester, told attendees. He also noted previous research exploring possible explanations for how MBSR programs might improve clinical symptoms of MS. One hypothesis involves an effect on the “forebrain limbic areas responsible for the neurobiological stress response.” Part of this study therefore involved looking for possible MRI changes before and after the MBSR program to test this hypothesis.

The study involved 23 patients, all women with relapsing remitting MS with an median age of 45, and 57% of whom were taking B cell–depleting agents. The patients’ average Expanded Disability Status Scale score was 2, and none experienced any new clinical or MRI disease activity during a 12-week observation period.

Patients volunteered to participate in the free 8-week MBSR program. Half attended MBSR classes in person while the other half had to attend virtual classes due to the pandemic. The program involved eight weekly 2.5-hour classes with daily homework assignments. The program, developed by Jon Kabat-Zinn at the University of Massachusetts, is intended to be “mental training for nonjudgmental awareness of moment-to-moment experience” that aims to “improve accuracy of perception, acceptance of intractable health-related changes, realistic sense of control, and appreciation of available life experiences,” Dr. Hemond said.

Among the 91% of participants who completed the course, 57% underwent both pre- and postcourse structural MRI scans, and 83% completed both the pre- and postcourse questionnaires. A subset of patients (53%) also provided blood samples for analysis of inflammatory gene expression markers.

“The conserved transcriptional response to adversity (CTRA) score was determined using well-established methods from 53 prespecified blood gene expression markers representing a composite of inflammation, interferon response, and immunoglobulin expression,” Dr. Hemond explained.

Participants’ average scores both pre- and post questionnaires revealed statistically significant improvements in stress, anxiety, depression, fatigue, loneliness, well-being, and interoceptive awareness (P < .01 for all).

Although precise values were not provided in the presentation, patients’ scores significantly decreased on the Brief Inventory of Perceived Stress (BIPS) for “lack of control,” “pushed,” and “conflict” (P < .03). Average scores also improved (decreased) on the Modified Fatigue Inventory Scale, the UCLA Loneliness Scale, and all three subscales of the Depression Anxiety Stress Scales assessment (P <.01). Participants’ scores increased on the Mental Health Continuum “hedonic” and “eudaimonic well-being” scales (P < .05).

Improvements on the Multidimensional Assessment of Interoceptive Awareness included self-regulation, attention regulation, “noticing” (P = .02), “not worrying” (P < .01), “emotional awareness” (P < .01), “body listening” (P < .01), and “trusting” (P < .01).

After adjustment for age, race, body mass index, medical therapy and time, the researchers found changes in inflammatory gene expression in the 12 participants who provided blood samples, and these changes correlated inversely with changes in their reported loneliness (P =.002), pain (P <.001), several interoception aspects (P < .01), and stress (P < .0001), particularly regarding feeling a lack of control.

Although no structural MRI changes were observed in the amygdala or prefrontal cortex, the researchers did see a 1% volume increase on the right-side hippocampus. Though the increase was significant (P < .01) and right hippocampal enlargement has been linked with MBSR in past studies, Dr. Hemond acknowledged the study’s small sample size and urged caution in interpreting that finding.

Dr. Hemond also reported that interaction between higher CTRA and the MSBR training attenuated the right hippocampal volume increase that was seen with MBSR, a finding which raises more questions than it answers.

The primary finding, however, was that “mindfulness-based stress reduction was associated with substantial improvement in multiple patient-reported outcomes of the debilitating ‘silent symptoms’ of MS,” Dr. Hemond told attendees. Though the study is limited by its small sample size, observational biases, and missing data, the findings suggest the possibility that MBSR is also associated with structural limbic brain changes, especially in the right hippocampus.
 

Another tool for managing MS

Ellen Mowry, MD, MCR, a professor of neurology and epidemiology at Johns Hopkins University, Baltimore, who attended the presentation, said she was very enthusiastic about this research.

“People with MS often are seeking ways that they can have self-efficacy and managing the symptoms of their disease, and we know that the disease-modifying therapies make a big difference, but we need additional therapies that can help people feel better and live better with MS,” Dr. Mowry commented.

She also acknowledged the challenges, however, in developing a mindfulness program that is accessible by a broad range of MS patients. This particular program involved several hours of work per day.

“People with MS often are either on the younger side, and they’re working and raising their family and doing all the same stuff that everybody else is doing, or they might be quite disabled and have more fatigue and other things that might make it really challenging to persist through that long of an intervention,” Dr. Mowry said.

The ideal program would be one that’s financially accessible, either through insurance, society more broadly, or another source, and which is logistically feasible for a wide range of patients. Finding a “sweet spot” with a program that doesn’t “require such a lengthy amount of time in order to see a success would be really great,” Dr. Mowry said. “You have to start somewhere, though, and you have to start with a program that’s already been tried and true and work from there.”
 

An online-only mindfulness program

One possible way to find that sweet spot is through an all-online program that patients access from home, similar to the 8-week MBSR program offered by Concord (N.H.) Hospital featured in the second study. The program was conducted via Zoom during once weekly synchronous meetings throughout 2021 and 2022 for eight cohorts of 5-15 participants each. The time of day the program was offered alternated between evening and daytime courses each quarter and was free for patients because of a hospital grant, according to Nicole Delcourt, BSN, RN, MSCN, of Concord Hospital Neurology, who facilitated patient sign-ups for the program.

Before and after each 8-week course, participants completed the PHQ-9, the PROMIS Cognitive Function, the PROMIS Fatigue–MS, and the Wasson Health Confidence assessments. Among the total 77 participating adults with MS, the completion rate was 81%, with 73% completing the preprogram assessments and 53% completed the postprogram assessments.

The assessments revealed a statistically significant increase in cognitive function and health confidence and decrease in depressive symptoms and fatigue following the program. Participants’ average PROMIS Cognitive Function scores increased from 16.7 before the program to 22.4 after, and their average Wasson Health Confidence score increased from 13.6 to 15.3 (P < .01 for both). Meanwhile, improvement in depressive symptoms was seen in participants’ decrease in Patient Health Questionnaire–9 scores from an average 6.9 to 4.6 (P = .01), and their average PROMIS Fatigue scores fell slightly but significantly from 59.3 to 55.3 (P < .05).

The participants “really felt like they were more in touch with their own feelings and emotions, and it helped them self-regulate,” Ms. Delcourt sad, “so it was really exciting.”

Patients also expressed satisfaction more subjectively in their feedback surveys. “I feel more aware of my body’s reactions to food and movement, and things that make me feel better physically,” one participant said. Another said that the class’s “lasting value ... will be to remember my own needs and how to become one with them.” Another participant praised the relevance of the printed and course materials, the speed of feedback on homework, and the quality of the video conference.

Dr. Hemond owns stock in VIVIO health. No other authors of either study reported other disclosures. Dr. Mowry has received grant funding from Biogen and Genentech. Ms. Delcourt had no disclosures. The in-person program study was funded by CMSC. Funding information for the Concord online program was unavailable.

CHICAGO – Patients with a certain type of brain tumor could soon be treated with an oral targeted drug instead of undergoing more toxic chemotherapy and radiation, say researchers reporting new results that could potentially change the treatment landscape.

The investigational drug vorasidenib (Servier) is awaiting approval for use in gliomas bearing mutations in IDH1 and IDH2.

Results from the pivotal phase 3 INDIGO trial show that the drug was associated with a significant delay in time to disease progression when compared with placebo.  

The median progression-free survival (PFS) was 27.7 months for patients on vorasidenib, compared with 11.1 months for patients assigned to placebo (hazard ratio for progression or death with vorasidenib of 0.39 (P < .0001).

Vorasidenib was also associated with significantly longer time to the next treatment, and patients generally tolerated the drug well, reported first author Ingo K. Mellinghoff, MD, from Memorial Sloan Kettering Cancer Center, New York.

The results show that “treatment with an oral precision medicine therapy can produce a reduction in the risk of tumor progression by 61%, so that is, we think, a significant sign of efficacy that has potential to change the landscape in this disease,” he commented.

Dr. Mellinghoff spoke at a media briefing prior to presenting the data at a plenary session at the annual meeting of the American Society of Clinical Oncology.

The study was published online in the New England Journal of Medicine to coincide with the presentation.

“What you just heard is a trial that was well done and well thought out: to use an oral, targeted, well-tolerated therapy to see if we could delay the use of our standard chemotherapy and radiation,” commented ASCO expert Glenn Lesser, MD, from Wake Forest Baptist Health in Winston-Salem, N.C., the invited discussant at the briefing.

“The results are quite striking and they’re statistically highly significant, and more importantly, they’re clinically very, very significant,” he continued.

“The results of this study really suggest that, in selected patients with IDH-mutant low-grade gliomas, we can potentially delay the use of these toxic chemotherapies and radiation, maybe for years if not many years, and as a result delay the long-term toxicities of those therapies in a group of patients who typically are experiencing long-term survival,” Dr. Lesser added.
 

Brain-penetrating oral drug

Vorasidenib is an oral inhibitor of the IDH1 and IDH2 enzymes, with the ability to cross the blood-brain barrier. Mutations in IDH1 are found in about 80% of grade 2 gliomas, and IDH2 mutations occur in about 4%.

Adjuvant chemoradiotherapy has become the standard of care for patients with IDH-mutant grade 3 gliomas and patients with IDH-mutant grade 2 tumors who are thought to be a high risk for early progression.

Many patients with IDH-mutant grade 2 gliomas are initially followed with serial MRI scans, with toxic therapies reserved for use after disease progression, Dr. Mellinghoff noted.

Vorasidenib offers the potential for delaying the use of more toxic therapies and the potential to alter the natural history of diffuse glioma while helping patients to maintain a good quality of life, he said.
 

Study details

The INDIGO trial involved 331 patients with grade 2 gliomas with IDH mutations, who were enrolled across 77 centers in 10 countries in North America, Europe, and the Middle East.

Patients were aged 12-80 years and had residual or recurrent grade 2 IDH1- or IDH2-mutated oligodendroglioma or astrocytoma, with measurable nonenhancing disease and no prior treatment for glioma (with the most recent surgery 1-5 years before randomization). They were eligible for the study if they were not in immediate need of chemotherapy and/or radiation.

After stratification by 1p/19q status and baseline tumor size, they were randomly assigned to receive either vorasidenib 40 mg daily or placebo in 28-day cycles.

At the second planned interim analysis data cutoff in September 2022, at a median follow-up of 14.2 months, 226 (68.3%) of the 331 patients remained on treatment.

The primary endpoint was median PFS by blinded independent central review, which as noted above was 16.6 months longer in those on the drug, compared with placebo.

The time to next therapy was also significantly longer with vorasidenib, with a median not yet reached, compared with 17.4 months for placebo (hazard ratio, 0.26, P < .001).

Adverse events of any grade occurring in more than 20% of those receiving vorasidenib were elevated liver enzymes, fatigue, headache, diarrhea, and nausea. Grade 3 or 4 ALT elevations occurred in 9.6% of patients assigned to vorasidenib, but not in the placebo group.

Vorasidenib received fast-track status from the Food and Drug Administration in March. It is currently being studied in a phase 1 trial in combination with pembrolizumab (Keytruda) in patients with grade 2/3 gliomas, and further exploration of the drug in combination with other agents is being considered.

The study was funded by Servier Pharmaceuticals, manufacturer of vorasidenib. Dr. Mellinghoff disclosed honoraria from Roche, a consulting or advisory role with Agios, Black Diamond Therapeutics, Debiopharm Group, Puma Biotechnology, Voyager Therapeutics, research funding from Amgen, General Electric, Lilly, and travel expenses from Agios, AstraZeneca, Puma Biotechnology, Roche, and Voyager Therapeutics. Dr. Lesser disclosed honoraria from SDP Oncology, consulting/advising for Cancer Expert Now, Agio, IN8bio, and Ono Pharmaceutical.

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

CHICAGO – Patients with a certain type of brain tumor could soon be treated with an oral targeted drug instead of undergoing more toxic chemotherapy and radiation, say researchers reporting new results that could potentially change the treatment landscape.

The investigational drug vorasidenib (Servier) is awaiting approval for use in gliomas bearing mutations in IDH1 and IDH2.

Results from the pivotal phase 3 INDIGO trial show that the drug was associated with a significant delay in time to disease progression when compared with placebo.  

The median progression-free survival (PFS) was 27.7 months for patients on vorasidenib, compared with 11.1 months for patients assigned to placebo (hazard ratio for progression or death with vorasidenib of 0.39 (P < .0001).

Vorasidenib was also associated with significantly longer time to the next treatment, and patients generally tolerated the drug well, reported first author Ingo K. Mellinghoff, MD, from Memorial Sloan Kettering Cancer Center, New York.

The results show that “treatment with an oral precision medicine therapy can produce a reduction in the risk of tumor progression by 61%, so that is, we think, a significant sign of efficacy that has potential to change the landscape in this disease,” he commented.

Dr. Mellinghoff spoke at a media briefing prior to presenting the data at a plenary session at the annual meeting of the American Society of Clinical Oncology.

The study was published online in the New England Journal of Medicine to coincide with the presentation.

“What you just heard is a trial that was well done and well thought out: to use an oral, targeted, well-tolerated therapy to see if we could delay the use of our standard chemotherapy and radiation,” commented ASCO expert Glenn Lesser, MD, from Wake Forest Baptist Health in Winston-Salem, N.C., the invited discussant at the briefing.

“The results are quite striking and they’re statistically highly significant, and more importantly, they’re clinically very, very significant,” he continued.

“The results of this study really suggest that, in selected patients with IDH-mutant low-grade gliomas, we can potentially delay the use of these toxic chemotherapies and radiation, maybe for years if not many years, and as a result delay the long-term toxicities of those therapies in a group of patients who typically are experiencing long-term survival,” Dr. Lesser added.
 

Brain-penetrating oral drug

Vorasidenib is an oral inhibitor of the IDH1 and IDH2 enzymes, with the ability to cross the blood-brain barrier. Mutations in IDH1 are found in about 80% of grade 2 gliomas, and IDH2 mutations occur in about 4%.

Adjuvant chemoradiotherapy has become the standard of care for patients with IDH-mutant grade 3 gliomas and patients with IDH-mutant grade 2 tumors who are thought to be a high risk for early progression.

Many patients with IDH-mutant grade 2 gliomas are initially followed with serial MRI scans, with toxic therapies reserved for use after disease progression, Dr. Mellinghoff noted.

Vorasidenib offers the potential for delaying the use of more toxic therapies and the potential to alter the natural history of diffuse glioma while helping patients to maintain a good quality of life, he said.
 

Study details

The INDIGO trial involved 331 patients with grade 2 gliomas with IDH mutations, who were enrolled across 77 centers in 10 countries in North America, Europe, and the Middle East.

Patients were aged 12-80 years and had residual or recurrent grade 2 IDH1- or IDH2-mutated oligodendroglioma or astrocytoma, with measurable nonenhancing disease and no prior treatment for glioma (with the most recent surgery 1-5 years before randomization). They were eligible for the study if they were not in immediate need of chemotherapy and/or radiation.

After stratification by 1p/19q status and baseline tumor size, they were randomly assigned to receive either vorasidenib 40 mg daily or placebo in 28-day cycles.

At the second planned interim analysis data cutoff in September 2022, at a median follow-up of 14.2 months, 226 (68.3%) of the 331 patients remained on treatment.

The primary endpoint was median PFS by blinded independent central review, which as noted above was 16.6 months longer in those on the drug, compared with placebo.

The time to next therapy was also significantly longer with vorasidenib, with a median not yet reached, compared with 17.4 months for placebo (hazard ratio, 0.26, P < .001).

Adverse events of any grade occurring in more than 20% of those receiving vorasidenib were elevated liver enzymes, fatigue, headache, diarrhea, and nausea. Grade 3 or 4 ALT elevations occurred in 9.6% of patients assigned to vorasidenib, but not in the placebo group.

Vorasidenib received fast-track status from the Food and Drug Administration in March. It is currently being studied in a phase 1 trial in combination with pembrolizumab (Keytruda) in patients with grade 2/3 gliomas, and further exploration of the drug in combination with other agents is being considered.

The study was funded by Servier Pharmaceuticals, manufacturer of vorasidenib. Dr. Mellinghoff disclosed honoraria from Roche, a consulting or advisory role with Agios, Black Diamond Therapeutics, Debiopharm Group, Puma Biotechnology, Voyager Therapeutics, research funding from Amgen, General Electric, Lilly, and travel expenses from Agios, AstraZeneca, Puma Biotechnology, Roche, and Voyager Therapeutics. Dr. Lesser disclosed honoraria from SDP Oncology, consulting/advising for Cancer Expert Now, Agio, IN8bio, and Ono Pharmaceutical.

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

CHICAGO – Patients with a certain type of brain tumor could soon be treated with an oral targeted drug instead of undergoing more toxic chemotherapy and radiation, say researchers reporting new results that could potentially change the treatment landscape.

The investigational drug vorasidenib (Servier) is awaiting approval for use in gliomas bearing mutations in IDH1 and IDH2.

Results from the pivotal phase 3 INDIGO trial show that the drug was associated with a significant delay in time to disease progression when compared with placebo.  

The median progression-free survival (PFS) was 27.7 months for patients on vorasidenib, compared with 11.1 months for patients assigned to placebo (hazard ratio for progression or death with vorasidenib of 0.39 (P < .0001).

Vorasidenib was also associated with significantly longer time to the next treatment, and patients generally tolerated the drug well, reported first author Ingo K. Mellinghoff, MD, from Memorial Sloan Kettering Cancer Center, New York.

The results show that “treatment with an oral precision medicine therapy can produce a reduction in the risk of tumor progression by 61%, so that is, we think, a significant sign of efficacy that has potential to change the landscape in this disease,” he commented.

Dr. Mellinghoff spoke at a media briefing prior to presenting the data at a plenary session at the annual meeting of the American Society of Clinical Oncology.

The study was published online in the New England Journal of Medicine to coincide with the presentation.

“What you just heard is a trial that was well done and well thought out: to use an oral, targeted, well-tolerated therapy to see if we could delay the use of our standard chemotherapy and radiation,” commented ASCO expert Glenn Lesser, MD, from Wake Forest Baptist Health in Winston-Salem, N.C., the invited discussant at the briefing.

“The results are quite striking and they’re statistically highly significant, and more importantly, they’re clinically very, very significant,” he continued.

“The results of this study really suggest that, in selected patients with IDH-mutant low-grade gliomas, we can potentially delay the use of these toxic chemotherapies and radiation, maybe for years if not many years, and as a result delay the long-term toxicities of those therapies in a group of patients who typically are experiencing long-term survival,” Dr. Lesser added.
 

Brain-penetrating oral drug

Vorasidenib is an oral inhibitor of the IDH1 and IDH2 enzymes, with the ability to cross the blood-brain barrier. Mutations in IDH1 are found in about 80% of grade 2 gliomas, and IDH2 mutations occur in about 4%.

Adjuvant chemoradiotherapy has become the standard of care for patients with IDH-mutant grade 3 gliomas and patients with IDH-mutant grade 2 tumors who are thought to be a high risk for early progression.

Many patients with IDH-mutant grade 2 gliomas are initially followed with serial MRI scans, with toxic therapies reserved for use after disease progression, Dr. Mellinghoff noted.

Vorasidenib offers the potential for delaying the use of more toxic therapies and the potential to alter the natural history of diffuse glioma while helping patients to maintain a good quality of life, he said.
 

Study details

The INDIGO trial involved 331 patients with grade 2 gliomas with IDH mutations, who were enrolled across 77 centers in 10 countries in North America, Europe, and the Middle East.

Patients were aged 12-80 years and had residual or recurrent grade 2 IDH1- or IDH2-mutated oligodendroglioma or astrocytoma, with measurable nonenhancing disease and no prior treatment for glioma (with the most recent surgery 1-5 years before randomization). They were eligible for the study if they were not in immediate need of chemotherapy and/or radiation.

After stratification by 1p/19q status and baseline tumor size, they were randomly assigned to receive either vorasidenib 40 mg daily or placebo in 28-day cycles.

At the second planned interim analysis data cutoff in September 2022, at a median follow-up of 14.2 months, 226 (68.3%) of the 331 patients remained on treatment.

The primary endpoint was median PFS by blinded independent central review, which as noted above was 16.6 months longer in those on the drug, compared with placebo.

The time to next therapy was also significantly longer with vorasidenib, with a median not yet reached, compared with 17.4 months for placebo (hazard ratio, 0.26, P < .001).

Adverse events of any grade occurring in more than 20% of those receiving vorasidenib were elevated liver enzymes, fatigue, headache, diarrhea, and nausea. Grade 3 or 4 ALT elevations occurred in 9.6% of patients assigned to vorasidenib, but not in the placebo group.

Vorasidenib received fast-track status from the Food and Drug Administration in March. It is currently being studied in a phase 1 trial in combination with pembrolizumab (Keytruda) in patients with grade 2/3 gliomas, and further exploration of the drug in combination with other agents is being considered.

The study was funded by Servier Pharmaceuticals, manufacturer of vorasidenib. Dr. Mellinghoff disclosed honoraria from Roche, a consulting or advisory role with Agios, Black Diamond Therapeutics, Debiopharm Group, Puma Biotechnology, Voyager Therapeutics, research funding from Amgen, General Electric, Lilly, and travel expenses from Agios, AstraZeneca, Puma Biotechnology, Roche, and Voyager Therapeutics. Dr. Lesser disclosed honoraria from SDP Oncology, consulting/advising for Cancer Expert Now, Agio, IN8bio, and Ono Pharmaceutical.

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

Taking a daily flavanol supplement improves hippocampal-dependent memory in older adults who have a relatively poor diet, results of a large new study suggest.

There’s increasing evidence that certain nutrients are important for the aging body and brain, study investigator Scott Small, MD, the Boris and Rose Katz Professor of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, told this news organization.

“With this new study, I think we can begin to say flavanols might be the first one that really is a nutrient for the aging brain.”

These findings, said Dr. Small, represent “the beginning of a new era” that will eventually lead to formal recommendations” related to ideal intake of flavanols to reduce cognitive aging.

The findings were published online in the Proceedings of the National Academy of Science.
 

Better cognitive aging

Cognitive aging refers to the decline in cognitive abilities that are not thought to be caused by neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Cognitive aging targets two areas of the brain: the hippocampus, which is related to memory function, and the prefrontal cortex, which is related to attention and executive function.

Previous research has linked flavanols, which are found in foods like apples, pears, berries, and cocoa beans, to improved cognitive aging. The evidence shows that consuming these nutrients might be associated with the hippocampal-dependent memory component of cognitive aging.

The new study, known as COcoa Supplement and Multivitamin Outcomes Study-Web (COSMOS-Web), included 3,562 generally healthy men and women, mean age 71 years, who were mostly well-educated and non-Hispanic/non-Latinx White individuals.

Participants were randomly assigned to receive oral flavanol-containing cocoa extract (500 mg of cocoa flavanols, including 80 mg of epicatechin) or a placebo daily.

The primary endpoint was hippocampal-dependent memory at year 1 as assessed with the ModRey, a neuropsychological test designed to measure hippocampal function.

Results showed participants in both groups had a typical learning (practice) effect, with similar improvements (d = 0.025; P = .42).

Researchers used other tests to measure cognition: the Color/Directional Flanker Task, a measure of prefrontal cortex function, and the ModBent, a measure that’s sensitive to dentate gyrus function. The flavanol intervention did not affect ModBent results or performance on the Flanker test after 1 year.

However, it was a different story for those with a poor diet at baseline. Researchers stratified participants into tertiles on the basis of diet quality as measured by the Healthy Eating Index (HEI) scores. Those in the lowest tertile had poorer baseline hippocampal-dependent memory performance but not memory related to the prefrontal cortex.

The flavanol intervention improved performance on the ModRey test, compared with placebo in participants in the low HEI tertile (overall effect: d = 0.086; P = .011) but not among those with a medium or high HEI at baseline.

“We confirmed that the flavanol intervention only benefits people who are relatively deficient at baseline,” said Dr. Small.

The correlation with hippocampal-dependent memory was confirmed in a subset of 1,361 study participants who provided a urine sample. Researchers measured urinary 5-(3′,4′-dihydroxyphenyl)-gamma-valerolactone metabolite (gVLM) concentrations, a validated biomarker of flavanol consumption.

After stratifying these results into tertiles, researchers found performance on the ModRey was significantly improved with the dietary flavanol intervention (overall effect: d = 0.141; P = .006) in the lowest gVLM tertile.
 

Memory restored

When participants in the lowest tertile consumed the supplement, “their flavanol levels went back to normal, and when that happened, their memory was restored,” said Dr. Small.

It appears that there is a sort of ceiling effect to the flavanol benefits. “It seems what you need to do is normalize your flavanol levels; if you go above normal, there was no evidence that your memory keeps on getting better,” said Dr. Small.

The study included only older adults, so it’s unclear what the impact of flavanol supplementation is in younger adults. But cognitive aging “begins its slippery side” in the 40s, said Dr. Small. “If this is truly a nutrient that is taken to prevent that slide from happening, it might be beneficial to start in our 40s.”

He recognized that the effect size is not large but said this is “very dependent” on baseline factors and most study participants had a rather healthy diet. “None of our participants were really highly deficient” in flavanols, he said.

“To see a stronger effect size, we need to do another study where we recruit people who are very low, truly deficient, in flavanols, and then see what happens.”

Showing that flavanols are linked to the hippocampal and not to the prefrontal component of cognitive aging “speaks to the mechanism,” said Dr. Small.

Though the exact mechanism linking flavanols with enhanced memory isn’t clear, there are some clues; for example, research suggests cognitive aging affects the dentate gyrus, a subregion of the hippocampus.

The flavanol supplements were well tolerated. “I can say with close to certainty that this is very safe,” said Dr. Small, adding the flavanols have now been used in numerous studies.

The findings suggest flavanol consumption might be part of future dietary guidelines. “I suspect that once there is sufficient evidence, flavanols will be part of the dietary recommendations for healthy aging,” said Dr. Small.
 

A word of caution

Heather M. Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, said that though science suggests a balanced diet is good for overall brain health, no single food, beverage, ingredient, vitamin, or supplement has yet been proven to prevent dementia, treat or cure Alzheimer’s, or benefit cognitive function or brain health.

Experts agree the best source of vitamins and other nutrients is from whole foods as part of a balanced diet. “We recognize that, for a variety of reasons, this may not always be possible,” said Dr. Snyder.

However, she noted, dietary supplements are not subject to the same rigorous review and regulation process as medications.

“The Alzheimer’s Association strongly encourages individuals to have conversations with their physicians about all medications and dietary supplements they are currently taking or interested in starting.” 

COSMOS is supported by an investigator-initiated grant from Mars Edge, a segment of Mars, company engaged in flavanol research and flavanol-related commercial activities, which included infrastructure support and the donation of study pills and packaging. Small reports receiving an unrestricted research grant from Mars.

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

Taking a daily flavanol supplement improves hippocampal-dependent memory in older adults who have a relatively poor diet, results of a large new study suggest.

There’s increasing evidence that certain nutrients are important for the aging body and brain, study investigator Scott Small, MD, the Boris and Rose Katz Professor of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, told this news organization.

“With this new study, I think we can begin to say flavanols might be the first one that really is a nutrient for the aging brain.”

These findings, said Dr. Small, represent “the beginning of a new era” that will eventually lead to formal recommendations” related to ideal intake of flavanols to reduce cognitive aging.

The findings were published online in the Proceedings of the National Academy of Science.
 

Better cognitive aging

Cognitive aging refers to the decline in cognitive abilities that are not thought to be caused by neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Cognitive aging targets two areas of the brain: the hippocampus, which is related to memory function, and the prefrontal cortex, which is related to attention and executive function.

Previous research has linked flavanols, which are found in foods like apples, pears, berries, and cocoa beans, to improved cognitive aging. The evidence shows that consuming these nutrients might be associated with the hippocampal-dependent memory component of cognitive aging.

The new study, known as COcoa Supplement and Multivitamin Outcomes Study-Web (COSMOS-Web), included 3,562 generally healthy men and women, mean age 71 years, who were mostly well-educated and non-Hispanic/non-Latinx White individuals.

Participants were randomly assigned to receive oral flavanol-containing cocoa extract (500 mg of cocoa flavanols, including 80 mg of epicatechin) or a placebo daily.

The primary endpoint was hippocampal-dependent memory at year 1 as assessed with the ModRey, a neuropsychological test designed to measure hippocampal function.

Results showed participants in both groups had a typical learning (practice) effect, with similar improvements (d = 0.025; P = .42).

Researchers used other tests to measure cognition: the Color/Directional Flanker Task, a measure of prefrontal cortex function, and the ModBent, a measure that’s sensitive to dentate gyrus function. The flavanol intervention did not affect ModBent results or performance on the Flanker test after 1 year.

However, it was a different story for those with a poor diet at baseline. Researchers stratified participants into tertiles on the basis of diet quality as measured by the Healthy Eating Index (HEI) scores. Those in the lowest tertile had poorer baseline hippocampal-dependent memory performance but not memory related to the prefrontal cortex.

The flavanol intervention improved performance on the ModRey test, compared with placebo in participants in the low HEI tertile (overall effect: d = 0.086; P = .011) but not among those with a medium or high HEI at baseline.

“We confirmed that the flavanol intervention only benefits people who are relatively deficient at baseline,” said Dr. Small.

The correlation with hippocampal-dependent memory was confirmed in a subset of 1,361 study participants who provided a urine sample. Researchers measured urinary 5-(3′,4′-dihydroxyphenyl)-gamma-valerolactone metabolite (gVLM) concentrations, a validated biomarker of flavanol consumption.

After stratifying these results into tertiles, researchers found performance on the ModRey was significantly improved with the dietary flavanol intervention (overall effect: d = 0.141; P = .006) in the lowest gVLM tertile.
 

Memory restored

When participants in the lowest tertile consumed the supplement, “their flavanol levels went back to normal, and when that happened, their memory was restored,” said Dr. Small.

It appears that there is a sort of ceiling effect to the flavanol benefits. “It seems what you need to do is normalize your flavanol levels; if you go above normal, there was no evidence that your memory keeps on getting better,” said Dr. Small.

The study included only older adults, so it’s unclear what the impact of flavanol supplementation is in younger adults. But cognitive aging “begins its slippery side” in the 40s, said Dr. Small. “If this is truly a nutrient that is taken to prevent that slide from happening, it might be beneficial to start in our 40s.”

He recognized that the effect size is not large but said this is “very dependent” on baseline factors and most study participants had a rather healthy diet. “None of our participants were really highly deficient” in flavanols, he said.

“To see a stronger effect size, we need to do another study where we recruit people who are very low, truly deficient, in flavanols, and then see what happens.”

Showing that flavanols are linked to the hippocampal and not to the prefrontal component of cognitive aging “speaks to the mechanism,” said Dr. Small.

Though the exact mechanism linking flavanols with enhanced memory isn’t clear, there are some clues; for example, research suggests cognitive aging affects the dentate gyrus, a subregion of the hippocampus.

The flavanol supplements were well tolerated. “I can say with close to certainty that this is very safe,” said Dr. Small, adding the flavanols have now been used in numerous studies.

The findings suggest flavanol consumption might be part of future dietary guidelines. “I suspect that once there is sufficient evidence, flavanols will be part of the dietary recommendations for healthy aging,” said Dr. Small.
 

A word of caution

Heather M. Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, said that though science suggests a balanced diet is good for overall brain health, no single food, beverage, ingredient, vitamin, or supplement has yet been proven to prevent dementia, treat or cure Alzheimer’s, or benefit cognitive function or brain health.

Experts agree the best source of vitamins and other nutrients is from whole foods as part of a balanced diet. “We recognize that, for a variety of reasons, this may not always be possible,” said Dr. Snyder.

However, she noted, dietary supplements are not subject to the same rigorous review and regulation process as medications.

“The Alzheimer’s Association strongly encourages individuals to have conversations with their physicians about all medications and dietary supplements they are currently taking or interested in starting.” 

COSMOS is supported by an investigator-initiated grant from Mars Edge, a segment of Mars, company engaged in flavanol research and flavanol-related commercial activities, which included infrastructure support and the donation of study pills and packaging. Small reports receiving an unrestricted research grant from Mars.

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

Taking a daily flavanol supplement improves hippocampal-dependent memory in older adults who have a relatively poor diet, results of a large new study suggest.

There’s increasing evidence that certain nutrients are important for the aging body and brain, study investigator Scott Small, MD, the Boris and Rose Katz Professor of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, told this news organization.

“With this new study, I think we can begin to say flavanols might be the first one that really is a nutrient for the aging brain.”

These findings, said Dr. Small, represent “the beginning of a new era” that will eventually lead to formal recommendations” related to ideal intake of flavanols to reduce cognitive aging.

The findings were published online in the Proceedings of the National Academy of Science.
 

Better cognitive aging

Cognitive aging refers to the decline in cognitive abilities that are not thought to be caused by neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Cognitive aging targets two areas of the brain: the hippocampus, which is related to memory function, and the prefrontal cortex, which is related to attention and executive function.

Previous research has linked flavanols, which are found in foods like apples, pears, berries, and cocoa beans, to improved cognitive aging. The evidence shows that consuming these nutrients might be associated with the hippocampal-dependent memory component of cognitive aging.

The new study, known as COcoa Supplement and Multivitamin Outcomes Study-Web (COSMOS-Web), included 3,562 generally healthy men and women, mean age 71 years, who were mostly well-educated and non-Hispanic/non-Latinx White individuals.

Participants were randomly assigned to receive oral flavanol-containing cocoa extract (500 mg of cocoa flavanols, including 80 mg of epicatechin) or a placebo daily.

The primary endpoint was hippocampal-dependent memory at year 1 as assessed with the ModRey, a neuropsychological test designed to measure hippocampal function.

Results showed participants in both groups had a typical learning (practice) effect, with similar improvements (d = 0.025; P = .42).

Researchers used other tests to measure cognition: the Color/Directional Flanker Task, a measure of prefrontal cortex function, and the ModBent, a measure that’s sensitive to dentate gyrus function. The flavanol intervention did not affect ModBent results or performance on the Flanker test after 1 year.

However, it was a different story for those with a poor diet at baseline. Researchers stratified participants into tertiles on the basis of diet quality as measured by the Healthy Eating Index (HEI) scores. Those in the lowest tertile had poorer baseline hippocampal-dependent memory performance but not memory related to the prefrontal cortex.

The flavanol intervention improved performance on the ModRey test, compared with placebo in participants in the low HEI tertile (overall effect: d = 0.086; P = .011) but not among those with a medium or high HEI at baseline.

“We confirmed that the flavanol intervention only benefits people who are relatively deficient at baseline,” said Dr. Small.

The correlation with hippocampal-dependent memory was confirmed in a subset of 1,361 study participants who provided a urine sample. Researchers measured urinary 5-(3′,4′-dihydroxyphenyl)-gamma-valerolactone metabolite (gVLM) concentrations, a validated biomarker of flavanol consumption.

After stratifying these results into tertiles, researchers found performance on the ModRey was significantly improved with the dietary flavanol intervention (overall effect: d = 0.141; P = .006) in the lowest gVLM tertile.
 

Memory restored

When participants in the lowest tertile consumed the supplement, “their flavanol levels went back to normal, and when that happened, their memory was restored,” said Dr. Small.

It appears that there is a sort of ceiling effect to the flavanol benefits. “It seems what you need to do is normalize your flavanol levels; if you go above normal, there was no evidence that your memory keeps on getting better,” said Dr. Small.

The study included only older adults, so it’s unclear what the impact of flavanol supplementation is in younger adults. But cognitive aging “begins its slippery side” in the 40s, said Dr. Small. “If this is truly a nutrient that is taken to prevent that slide from happening, it might be beneficial to start in our 40s.”

He recognized that the effect size is not large but said this is “very dependent” on baseline factors and most study participants had a rather healthy diet. “None of our participants were really highly deficient” in flavanols, he said.

“To see a stronger effect size, we need to do another study where we recruit people who are very low, truly deficient, in flavanols, and then see what happens.”

Showing that flavanols are linked to the hippocampal and not to the prefrontal component of cognitive aging “speaks to the mechanism,” said Dr. Small.

Though the exact mechanism linking flavanols with enhanced memory isn’t clear, there are some clues; for example, research suggests cognitive aging affects the dentate gyrus, a subregion of the hippocampus.

The flavanol supplements were well tolerated. “I can say with close to certainty that this is very safe,” said Dr. Small, adding the flavanols have now been used in numerous studies.

The findings suggest flavanol consumption might be part of future dietary guidelines. “I suspect that once there is sufficient evidence, flavanols will be part of the dietary recommendations for healthy aging,” said Dr. Small.
 

A word of caution

Heather M. Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, said that though science suggests a balanced diet is good for overall brain health, no single food, beverage, ingredient, vitamin, or supplement has yet been proven to prevent dementia, treat or cure Alzheimer’s, or benefit cognitive function or brain health.

Experts agree the best source of vitamins and other nutrients is from whole foods as part of a balanced diet. “We recognize that, for a variety of reasons, this may not always be possible,” said Dr. Snyder.

However, she noted, dietary supplements are not subject to the same rigorous review and regulation process as medications.

“The Alzheimer’s Association strongly encourages individuals to have conversations with their physicians about all medications and dietary supplements they are currently taking or interested in starting.” 

COSMOS is supported by an investigator-initiated grant from Mars Edge, a segment of Mars, company engaged in flavanol research and flavanol-related commercial activities, which included infrastructure support and the donation of study pills and packaging. Small reports receiving an unrestricted research grant from Mars.

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

Autologous hematopoietic stem cell transplant (AHSCT) is more effective than fingolimod and natalizumab for patients with highly active relapsing-remitting multiple sclerosis (MS), data indicate.

In a multicenter study that emulated pairwise trials, AHSCT was associated with a higher likelihood of disability improvement, compared with fingolimod (hazard ratio, 2.70).

Once the immune system is reconstituted, it can contribute to the healing process. AHSCT thus provides the possibility of improvement in MS. Disease-modifying therapies that require continued use, however, could inhibit that process.

“If you can stop the inflammation that’s driving this disease fairly early on, [patients] do have the capacity to repair,” said study author Mark Freedman, MD, a professor of neurology at the University of Ottawa. “And we start to see that especially in a treatment [like AHSCT] where you don’t maintain the hit on the immune system.”

The study was published online in JAMA Neurology.
 

Pairwise analyses

Single-arm studies and an open-label, randomized trial have suggested that AHSCT has efficacy. The regimen is associated with a 0.3%-2.0% risk for mortality, but this risk has declined with better patient selection and clinical experience, according to the researchers. Comparative studies of AHSCT and DMTs are needed, but they are difficult to carry out, which is why the current team chose a propensity-score matched case–control design, according to lead author Tomas Kalincik, MD, PhD, head of the University of Melbourne’s Clinical Outcomes Research Unit.

The researchers examined data from 4,915 patients with relapsing-remitting MS. Of this population, 3.4% received AHSCT, 52.0% received fingolimod, 30.3% received natalizumab, and 14.2% received ocrelizumab. The proportion of women in the treatment groups ranged from 65% to 70%.

The researchers used pairwise matching to simulate the randomized, controlled trials comparing AHSCT with fingolimod, natalizumab, and ocrelizumab. Patients were matched on the basis of sex, age, disability, relapse events at 12 and 24 months before baseline, time from first symptoms to baseline, the most effective previous DMT, and geographical region.

Compared with fingolimod, AHSCT was associated with fewer relapses (annualized relapse rate, 0.09 vs. 0.20; P < .001). This finding was confirmed by a reduced cumulative hazard of relapse (HR, 0.26).

Compared with natalizumab, AHSCT had only a modestly greater effect on annualized relapse rates (ARR, 0.08 vs. 0.10; P = .03), with a cumulative HR for relapses of 0.51.

There was no significant difference in the risk for relapse between treatment with AHSCT and with ocrelizumab (ARR, 0.09 vs. 0.06; P = .86), nor was the risk of cumulative relapses significantly different between these treatments.

Among patients included in the pairwise analyses who received AHSCT, 23.3% developed febrile neutropenia during mobilization, 11.3% developed serum sickness, and 8.8% were admitted to an intensive care unit. There were 82 serious adverse events among 58 patients after they were discharged post AHSCT treatment, including infections (59.8% of adverse events) that were primarily due to viral sources (41.5% of adverse events). There was one death (0.6%) due to veno-occlusive disease of the liver following busulfan exposure.

Some AHSCT protocols are stronger than others, and milder immune ablative measures are less likely to produce lasting effects. “We completely remove the old immune system and put in a brand new one,” said Dr. Freedman, referring to the practice at his center. “That’s a fairly horrendous procedure, and, not surprisingly, we’ve had a slight increase in the types of side effects, compared with other groups who don’t use that heavy-duty conditioning regimen, but we’ve had absolutely zero return of inflammatory events over 23 years that we’ve been doing this. Nobody’s had another attack, no one has even developed a single new MRI lesion.”

The so-called medium and light conditioning regimens are associated with a return of disease activity in about 25% of patients within 3 years, Dr. Freedman added. “You start to see new MRI lesions form and relapses occurring. It’s still better than any of the higher efficacy therapies, but it’s not stopped the disease.”

A key limitation of the study is that its efficacy analysis did not distinguish between different intensities of AHSCT regimens, according to the authors.
 

Encouraging results

AHSCT is highly effective at temporarily eliminating inflammation in the central nervous system, according to Jeffrey Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, and Anne Cross, MD, professor of neurology at Washington University, St. Louis, who wrote an editorial that accompanied the study. As many as 35% of patients require DMTs at some point after AHSCT.

The results of the new study are encouraging, but plenty of unanswered questions remain, Dr. Cohen said. “Many studies demonstrate AHSCT to have potent durable efficacy that appears to be greater than that of the available DMTs, but some studies – for example, this one – suggest that AHSCT may be superior to some but not all DMTs. Therefore, where to place AHSCT in the overall treatment sequence remains uncertain.” Randomized, controlled trials that are now in process “hopefully will clarify,” he added.

The study was supported by the National Health and Medical Research Council of Australia, Multiple Sclerosis Australia, and the MS Foundation of Canada. Dr. Kalincik has financial relationships with Eisai, Novartis, Biogen, Merck, Roche, Sanofi Genzyme, Teva, Celgene, Bristol-Myers Squibb, and Janssen. Dr. Freedman has financial relationships with Sanofi-Genzyme Canada, Alexion, Atara Biotherapeutics, Bayer Healthcare, Beigene, BMS (Celgene), EMD, Hoffmann-La Roche, Janssen, Merck Serono, Quanterix, Novartis, Sanofi-Genzyme, Teva Canada Innovation, Celestra Health, McKesson, and EMD Serono. Dr. Cohen has financial relationships with Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI.

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

Autologous hematopoietic stem cell transplant (AHSCT) is more effective than fingolimod and natalizumab for patients with highly active relapsing-remitting multiple sclerosis (MS), data indicate.

In a multicenter study that emulated pairwise trials, AHSCT was associated with a higher likelihood of disability improvement, compared with fingolimod (hazard ratio, 2.70).

Once the immune system is reconstituted, it can contribute to the healing process. AHSCT thus provides the possibility of improvement in MS. Disease-modifying therapies that require continued use, however, could inhibit that process.

“If you can stop the inflammation that’s driving this disease fairly early on, [patients] do have the capacity to repair,” said study author Mark Freedman, MD, a professor of neurology at the University of Ottawa. “And we start to see that especially in a treatment [like AHSCT] where you don’t maintain the hit on the immune system.”

The study was published online in JAMA Neurology.
 

Pairwise analyses

Single-arm studies and an open-label, randomized trial have suggested that AHSCT has efficacy. The regimen is associated with a 0.3%-2.0% risk for mortality, but this risk has declined with better patient selection and clinical experience, according to the researchers. Comparative studies of AHSCT and DMTs are needed, but they are difficult to carry out, which is why the current team chose a propensity-score matched case–control design, according to lead author Tomas Kalincik, MD, PhD, head of the University of Melbourne’s Clinical Outcomes Research Unit.

The researchers examined data from 4,915 patients with relapsing-remitting MS. Of this population, 3.4% received AHSCT, 52.0% received fingolimod, 30.3% received natalizumab, and 14.2% received ocrelizumab. The proportion of women in the treatment groups ranged from 65% to 70%.

The researchers used pairwise matching to simulate the randomized, controlled trials comparing AHSCT with fingolimod, natalizumab, and ocrelizumab. Patients were matched on the basis of sex, age, disability, relapse events at 12 and 24 months before baseline, time from first symptoms to baseline, the most effective previous DMT, and geographical region.

Compared with fingolimod, AHSCT was associated with fewer relapses (annualized relapse rate, 0.09 vs. 0.20; P < .001). This finding was confirmed by a reduced cumulative hazard of relapse (HR, 0.26).

Compared with natalizumab, AHSCT had only a modestly greater effect on annualized relapse rates (ARR, 0.08 vs. 0.10; P = .03), with a cumulative HR for relapses of 0.51.

There was no significant difference in the risk for relapse between treatment with AHSCT and with ocrelizumab (ARR, 0.09 vs. 0.06; P = .86), nor was the risk of cumulative relapses significantly different between these treatments.

Among patients included in the pairwise analyses who received AHSCT, 23.3% developed febrile neutropenia during mobilization, 11.3% developed serum sickness, and 8.8% were admitted to an intensive care unit. There were 82 serious adverse events among 58 patients after they were discharged post AHSCT treatment, including infections (59.8% of adverse events) that were primarily due to viral sources (41.5% of adverse events). There was one death (0.6%) due to veno-occlusive disease of the liver following busulfan exposure.

Some AHSCT protocols are stronger than others, and milder immune ablative measures are less likely to produce lasting effects. “We completely remove the old immune system and put in a brand new one,” said Dr. Freedman, referring to the practice at his center. “That’s a fairly horrendous procedure, and, not surprisingly, we’ve had a slight increase in the types of side effects, compared with other groups who don’t use that heavy-duty conditioning regimen, but we’ve had absolutely zero return of inflammatory events over 23 years that we’ve been doing this. Nobody’s had another attack, no one has even developed a single new MRI lesion.”

The so-called medium and light conditioning regimens are associated with a return of disease activity in about 25% of patients within 3 years, Dr. Freedman added. “You start to see new MRI lesions form and relapses occurring. It’s still better than any of the higher efficacy therapies, but it’s not stopped the disease.”

A key limitation of the study is that its efficacy analysis did not distinguish between different intensities of AHSCT regimens, according to the authors.
 

Encouraging results

AHSCT is highly effective at temporarily eliminating inflammation in the central nervous system, according to Jeffrey Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, and Anne Cross, MD, professor of neurology at Washington University, St. Louis, who wrote an editorial that accompanied the study. As many as 35% of patients require DMTs at some point after AHSCT.

The results of the new study are encouraging, but plenty of unanswered questions remain, Dr. Cohen said. “Many studies demonstrate AHSCT to have potent durable efficacy that appears to be greater than that of the available DMTs, but some studies – for example, this one – suggest that AHSCT may be superior to some but not all DMTs. Therefore, where to place AHSCT in the overall treatment sequence remains uncertain.” Randomized, controlled trials that are now in process “hopefully will clarify,” he added.

The study was supported by the National Health and Medical Research Council of Australia, Multiple Sclerosis Australia, and the MS Foundation of Canada. Dr. Kalincik has financial relationships with Eisai, Novartis, Biogen, Merck, Roche, Sanofi Genzyme, Teva, Celgene, Bristol-Myers Squibb, and Janssen. Dr. Freedman has financial relationships with Sanofi-Genzyme Canada, Alexion, Atara Biotherapeutics, Bayer Healthcare, Beigene, BMS (Celgene), EMD, Hoffmann-La Roche, Janssen, Merck Serono, Quanterix, Novartis, Sanofi-Genzyme, Teva Canada Innovation, Celestra Health, McKesson, and EMD Serono. Dr. Cohen has financial relationships with Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI.

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

Autologous hematopoietic stem cell transplant (AHSCT) is more effective than fingolimod and natalizumab for patients with highly active relapsing-remitting multiple sclerosis (MS), data indicate.

In a multicenter study that emulated pairwise trials, AHSCT was associated with a higher likelihood of disability improvement, compared with fingolimod (hazard ratio, 2.70).

Once the immune system is reconstituted, it can contribute to the healing process. AHSCT thus provides the possibility of improvement in MS. Disease-modifying therapies that require continued use, however, could inhibit that process.

“If you can stop the inflammation that’s driving this disease fairly early on, [patients] do have the capacity to repair,” said study author Mark Freedman, MD, a professor of neurology at the University of Ottawa. “And we start to see that especially in a treatment [like AHSCT] where you don’t maintain the hit on the immune system.”

The study was published online in JAMA Neurology.
 

Pairwise analyses

Single-arm studies and an open-label, randomized trial have suggested that AHSCT has efficacy. The regimen is associated with a 0.3%-2.0% risk for mortality, but this risk has declined with better patient selection and clinical experience, according to the researchers. Comparative studies of AHSCT and DMTs are needed, but they are difficult to carry out, which is why the current team chose a propensity-score matched case–control design, according to lead author Tomas Kalincik, MD, PhD, head of the University of Melbourne’s Clinical Outcomes Research Unit.

The researchers examined data from 4,915 patients with relapsing-remitting MS. Of this population, 3.4% received AHSCT, 52.0% received fingolimod, 30.3% received natalizumab, and 14.2% received ocrelizumab. The proportion of women in the treatment groups ranged from 65% to 70%.

The researchers used pairwise matching to simulate the randomized, controlled trials comparing AHSCT with fingolimod, natalizumab, and ocrelizumab. Patients were matched on the basis of sex, age, disability, relapse events at 12 and 24 months before baseline, time from first symptoms to baseline, the most effective previous DMT, and geographical region.

Compared with fingolimod, AHSCT was associated with fewer relapses (annualized relapse rate, 0.09 vs. 0.20; P < .001). This finding was confirmed by a reduced cumulative hazard of relapse (HR, 0.26).

Compared with natalizumab, AHSCT had only a modestly greater effect on annualized relapse rates (ARR, 0.08 vs. 0.10; P = .03), with a cumulative HR for relapses of 0.51.

There was no significant difference in the risk for relapse between treatment with AHSCT and with ocrelizumab (ARR, 0.09 vs. 0.06; P = .86), nor was the risk of cumulative relapses significantly different between these treatments.

Among patients included in the pairwise analyses who received AHSCT, 23.3% developed febrile neutropenia during mobilization, 11.3% developed serum sickness, and 8.8% were admitted to an intensive care unit. There were 82 serious adverse events among 58 patients after they were discharged post AHSCT treatment, including infections (59.8% of adverse events) that were primarily due to viral sources (41.5% of adverse events). There was one death (0.6%) due to veno-occlusive disease of the liver following busulfan exposure.

Some AHSCT protocols are stronger than others, and milder immune ablative measures are less likely to produce lasting effects. “We completely remove the old immune system and put in a brand new one,” said Dr. Freedman, referring to the practice at his center. “That’s a fairly horrendous procedure, and, not surprisingly, we’ve had a slight increase in the types of side effects, compared with other groups who don’t use that heavy-duty conditioning regimen, but we’ve had absolutely zero return of inflammatory events over 23 years that we’ve been doing this. Nobody’s had another attack, no one has even developed a single new MRI lesion.”

The so-called medium and light conditioning regimens are associated with a return of disease activity in about 25% of patients within 3 years, Dr. Freedman added. “You start to see new MRI lesions form and relapses occurring. It’s still better than any of the higher efficacy therapies, but it’s not stopped the disease.”

A key limitation of the study is that its efficacy analysis did not distinguish between different intensities of AHSCT regimens, according to the authors.
 

Encouraging results

AHSCT is highly effective at temporarily eliminating inflammation in the central nervous system, according to Jeffrey Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, and Anne Cross, MD, professor of neurology at Washington University, St. Louis, who wrote an editorial that accompanied the study. As many as 35% of patients require DMTs at some point after AHSCT.

The results of the new study are encouraging, but plenty of unanswered questions remain, Dr. Cohen said. “Many studies demonstrate AHSCT to have potent durable efficacy that appears to be greater than that of the available DMTs, but some studies – for example, this one – suggest that AHSCT may be superior to some but not all DMTs. Therefore, where to place AHSCT in the overall treatment sequence remains uncertain.” Randomized, controlled trials that are now in process “hopefully will clarify,” he added.

The study was supported by the National Health and Medical Research Council of Australia, Multiple Sclerosis Australia, and the MS Foundation of Canada. Dr. Kalincik has financial relationships with Eisai, Novartis, Biogen, Merck, Roche, Sanofi Genzyme, Teva, Celgene, Bristol-Myers Squibb, and Janssen. Dr. Freedman has financial relationships with Sanofi-Genzyme Canada, Alexion, Atara Biotherapeutics, Bayer Healthcare, Beigene, BMS (Celgene), EMD, Hoffmann-La Roche, Janssen, Merck Serono, Quanterix, Novartis, Sanofi-Genzyme, Teva Canada Innovation, Celestra Health, McKesson, and EMD Serono. Dr. Cohen has financial relationships with Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI.

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

The Centers for Medicare & Medicaid Services has announced that Medicare will cover drugs designed to slow Alzheimer’s disease once they receive traditional approval by the Food and Drug Administration.

The one caveat is that CMS will require physicians to participate in registries that collect evidence about how these drugs work in the real world.

Physicians will be able to submit this evidence through a nationwide, CMS-facilitated portal that will be available when any product gains traditional approval and will collect information via an easy-to-use format.

“If the FDA grants traditional approval, then Medicare will cover it in appropriate settings that also support the collection of real-world information to study the usefulness of these drugs for people with Medicare,” the CMS says in a news release.

“CMS has always been committed to helping people obtain timely access to innovative treatments that meaningfully improve care and outcomes for this disease,” added CMS Administrator Chiquita Brooks-LaSure.

“If the FDA grants traditional approval, CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered,” Ms. Brooks-LaSure explained.

The CMS says broader Medicare coverage for an Alzheimer’s drug would begin on the same day the FDA grants traditional approval. Under CMS’ current coverage policy, if the FDA grants traditional approval to other drugs in this class, they would also be eligible for broader coverage.

Currently two drugs in this class – aducanumab (Aduhelm) and lecanemab (Leqembi) – have received accelerated approval from the FDA, but no product has received traditional approval.

Lecanemab might be the first to cross the line.

On June 9, the FDA Peripheral and Central Nervous System Drugs Advisory Committee will discuss results of a confirmatory trial of lecanemab, with a potential decision on traditional approval expected shortly thereafter.

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

The Centers for Medicare & Medicaid Services has announced that Medicare will cover drugs designed to slow Alzheimer’s disease once they receive traditional approval by the Food and Drug Administration.

The one caveat is that CMS will require physicians to participate in registries that collect evidence about how these drugs work in the real world.

Physicians will be able to submit this evidence through a nationwide, CMS-facilitated portal that will be available when any product gains traditional approval and will collect information via an easy-to-use format.

“If the FDA grants traditional approval, then Medicare will cover it in appropriate settings that also support the collection of real-world information to study the usefulness of these drugs for people with Medicare,” the CMS says in a news release.

“CMS has always been committed to helping people obtain timely access to innovative treatments that meaningfully improve care and outcomes for this disease,” added CMS Administrator Chiquita Brooks-LaSure.

“If the FDA grants traditional approval, CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered,” Ms. Brooks-LaSure explained.

The CMS says broader Medicare coverage for an Alzheimer’s drug would begin on the same day the FDA grants traditional approval. Under CMS’ current coverage policy, if the FDA grants traditional approval to other drugs in this class, they would also be eligible for broader coverage.

Currently two drugs in this class – aducanumab (Aduhelm) and lecanemab (Leqembi) – have received accelerated approval from the FDA, but no product has received traditional approval.

Lecanemab might be the first to cross the line.

On June 9, the FDA Peripheral and Central Nervous System Drugs Advisory Committee will discuss results of a confirmatory trial of lecanemab, with a potential decision on traditional approval expected shortly thereafter.

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

The Centers for Medicare & Medicaid Services has announced that Medicare will cover drugs designed to slow Alzheimer’s disease once they receive traditional approval by the Food and Drug Administration.

The one caveat is that CMS will require physicians to participate in registries that collect evidence about how these drugs work in the real world.

Physicians will be able to submit this evidence through a nationwide, CMS-facilitated portal that will be available when any product gains traditional approval and will collect information via an easy-to-use format.

“If the FDA grants traditional approval, then Medicare will cover it in appropriate settings that also support the collection of real-world information to study the usefulness of these drugs for people with Medicare,” the CMS says in a news release.

“CMS has always been committed to helping people obtain timely access to innovative treatments that meaningfully improve care and outcomes for this disease,” added CMS Administrator Chiquita Brooks-LaSure.

“If the FDA grants traditional approval, CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered,” Ms. Brooks-LaSure explained.

The CMS says broader Medicare coverage for an Alzheimer’s drug would begin on the same day the FDA grants traditional approval. Under CMS’ current coverage policy, if the FDA grants traditional approval to other drugs in this class, they would also be eligible for broader coverage.

Currently two drugs in this class – aducanumab (Aduhelm) and lecanemab (Leqembi) – have received accelerated approval from the FDA, but no product has received traditional approval.

Lecanemab might be the first to cross the line.

On June 9, the FDA Peripheral and Central Nervous System Drugs Advisory Committee will discuss results of a confirmatory trial of lecanemab, with a potential decision on traditional approval expected shortly thereafter.

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