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Hypertension is associated with more than a twofold increased risk of developing late-onset epilepsy even in patients who have not had a previous stroke, new research suggests.

After excluding individuals with normal blood pressure who were taking antihypertensive medication, investigators found hypertension was linked to an almost 2.5-fold higher risk of epilepsy.

“Our findings further expand upon our knowledge of the negative effects hypertension has on brain health and, regarding epilepsy, that effect may be starting even in midlife,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University.

“Practicing clinicians should be vigilant to diagnose hypertension, discuss with patients all potential long-term brain health outcomes, and need for treatment. Furthermore, in those presenting with new-onset epilepsy later in life, screening for potentially undiagnosed hypertension should be included in the initial workup,” she said.

The study was published online Nov. 17, 2021, in Epilepsia.
 

Unknown etiology

“New-onset epilepsy risk increases with increasing age over the age of 65 and can affect 15-20 per 1,000 older individuals. Although the most common causes for seizures in this age group are prior history of stroke and presence of dementia, for about 30%-40% of patients, the etiology of seizures remains unknown,” Dr. Stefanidou said.

“We wanted to study if modifiable vascular risk factors that are known to contribute both to vascular brain aging and to neurodegeneration may directly predict the development of epilepsy, even in the absence of clinical stroke or dementia,” she added.

To investigate, the researchers turned to data from participants in the Offspring Cohort of the Framingham Health Study (FHS). The original FHS was an ongoing longitudinal community-based study that first began in 1948. Offspring of the original cohort and their spouses (n = 5,124) were enrolled in the Offspring Cohort in 1971, with surveillance of these second-generation participants based on exam visits occurring every 4 years.

The study included participants who had attended exam 5 (1991-1995), were age 45 years or older, had available vascular risk factor (VRF) data, and available follow-up data on epilepsy status (n = 2,986; mean age, 58 years; 48% male).

The investigators conducted two statistical analyses. In the primary model, they adjusted for age and gender, while in a secondary model they also adjusted for prevalent and interim stroke. They also conducted an analysis that excluded participants treated with antihypertensive medication and had normal blood pressure.
 

Plausible mechanisms

During a mean follow-up of 19.2 years, 55 incident epilepsy cases were identified. The mean age of these patients was 73.8 years.

In the primary model, hypertension was associated with an almost twofold higher risk of developing epilepsy (hazard ratio, 1.97; 95% confidence interval, 1.13-3.45; P = .017).

Interestingly, the Framingham Stroke Risk Profile – a calculation based on an array of factors, including age/sex, systolic blood pressure, antihypertensive therapy, diabetes, history of cardiovascular disease, atrial fibrillation, and cigarette smoking – was not associated with incident epilepsy, and there was no other significant associated between any of the other VRFs when looked at independently.

When the researchers adjusted for prevalent and interim stroke, they continued to find an almost twofold higher risk of developing epilepsy (HR 1.93; 95% CI, 1.10-3.37; P = .022). An analysis that adjusted for competing risk of death obtained similar findings (HR, 1.98; 95% CI, 1.03-3.81; P = .042).

The model that excluded patients receiving antihypertensive treatment, whose blood pressure readings were normal (n = 2,162; 50 incident epilepsy cases) showed an even stronger association (HR, 2.44; 95% CI, 1.36-4.35; P = .003).

“Our results are based on an epidemiological, observational study, therefore our findings point to an association between hypertension and new-onset epilepsy later in life,” said Dr. Stefanidou.

She noted that because it was an observational study, “a cause-effect relationship cannot be established based on these results, but there is growing evidence from our, as well as other, similar cohorts that hypertension, a modifiable vascular risk factor, may indeed be an independent predictor of late-onset epilepsy.”

There are “plausible mechanisms” that support both a direct, and indirect, role of hypertension – for example, through accumulation of small vessel disease in the brain – but further research will be necessary to elucidate the exact mechanisms involved in the process,” she added.
 

‘Welcome addition’

In a joint comment, Hedley C.A. Emsley, PhD, professor of clinical neuroscience, Lancaster (England) University, and Jasmine Wall, MBBChir, academic clinical fellow in neurology, Lancaster University, described the study as a “welcome addition to this field,” noting that the Framingham Heart Study “lends itself well to an embedded observational study of this nature of late-onset epilepsy.”

Dr. Emsley and Dr. Wall, who were not involved in the research, said that the “apparent magnitude of increased late-onset epilepsy risk association with hypertension in the Stefanidou et al study is quite striking,” even allowing for the “relatively small sample size,” since their analysis and findings appear to “withstand exclusion of individuals who became normotensive on antihypertensive treatment.”

They noted that in recent years there has been a growing body of evidence highlighting the importance of hypertension in late-onset epilepsy epileptogenesis with subclinical cerebrovascular diseases, including “otherwise occult cerebral small vessel disease believed to be a frequent cause.”

The mechanisms “remain unclear,” but they could potentially include diffuse cerebral microangiopathy, structural and physiological changes, and/or blood-brain barrier dysfunction and leakage, they suggested.

“Although there is no current consensus over an age threshold that defines ‘late onset,’ we would argue that age thresholds used in such studies of late-onset epilepsy should be lower, to avoid missing younger adults at risk through vascular mechanisms,” Dr. Emsley and Dr. Wall added.

The study authors suggest that “potential pathophysiologic mechanisms can further be explored in future experimental studies and clinical trials.”

This study was funded by grants from the National Institutes of Health and Finding a Cure for Epilepsy/Seizures. Dr. Stefanidou disclosed relevant financial relationships. Dr. Emsley and Dr. Wall disclosed no relevant financial relationships.

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

Hypertension is associated with more than a twofold increased risk of developing late-onset epilepsy even in patients who have not had a previous stroke, new research suggests.

After excluding individuals with normal blood pressure who were taking antihypertensive medication, investigators found hypertension was linked to an almost 2.5-fold higher risk of epilepsy.

“Our findings further expand upon our knowledge of the negative effects hypertension has on brain health and, regarding epilepsy, that effect may be starting even in midlife,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University.

“Practicing clinicians should be vigilant to diagnose hypertension, discuss with patients all potential long-term brain health outcomes, and need for treatment. Furthermore, in those presenting with new-onset epilepsy later in life, screening for potentially undiagnosed hypertension should be included in the initial workup,” she said.

The study was published online Nov. 17, 2021, in Epilepsia.
 

Unknown etiology

“New-onset epilepsy risk increases with increasing age over the age of 65 and can affect 15-20 per 1,000 older individuals. Although the most common causes for seizures in this age group are prior history of stroke and presence of dementia, for about 30%-40% of patients, the etiology of seizures remains unknown,” Dr. Stefanidou said.

“We wanted to study if modifiable vascular risk factors that are known to contribute both to vascular brain aging and to neurodegeneration may directly predict the development of epilepsy, even in the absence of clinical stroke or dementia,” she added.

To investigate, the researchers turned to data from participants in the Offspring Cohort of the Framingham Health Study (FHS). The original FHS was an ongoing longitudinal community-based study that first began in 1948. Offspring of the original cohort and their spouses (n = 5,124) were enrolled in the Offspring Cohort in 1971, with surveillance of these second-generation participants based on exam visits occurring every 4 years.

The study included participants who had attended exam 5 (1991-1995), were age 45 years or older, had available vascular risk factor (VRF) data, and available follow-up data on epilepsy status (n = 2,986; mean age, 58 years; 48% male).

The investigators conducted two statistical analyses. In the primary model, they adjusted for age and gender, while in a secondary model they also adjusted for prevalent and interim stroke. They also conducted an analysis that excluded participants treated with antihypertensive medication and had normal blood pressure.
 

Plausible mechanisms

During a mean follow-up of 19.2 years, 55 incident epilepsy cases were identified. The mean age of these patients was 73.8 years.

In the primary model, hypertension was associated with an almost twofold higher risk of developing epilepsy (hazard ratio, 1.97; 95% confidence interval, 1.13-3.45; P = .017).

Interestingly, the Framingham Stroke Risk Profile – a calculation based on an array of factors, including age/sex, systolic blood pressure, antihypertensive therapy, diabetes, history of cardiovascular disease, atrial fibrillation, and cigarette smoking – was not associated with incident epilepsy, and there was no other significant associated between any of the other VRFs when looked at independently.

When the researchers adjusted for prevalent and interim stroke, they continued to find an almost twofold higher risk of developing epilepsy (HR 1.93; 95% CI, 1.10-3.37; P = .022). An analysis that adjusted for competing risk of death obtained similar findings (HR, 1.98; 95% CI, 1.03-3.81; P = .042).

The model that excluded patients receiving antihypertensive treatment, whose blood pressure readings were normal (n = 2,162; 50 incident epilepsy cases) showed an even stronger association (HR, 2.44; 95% CI, 1.36-4.35; P = .003).

“Our results are based on an epidemiological, observational study, therefore our findings point to an association between hypertension and new-onset epilepsy later in life,” said Dr. Stefanidou.

She noted that because it was an observational study, “a cause-effect relationship cannot be established based on these results, but there is growing evidence from our, as well as other, similar cohorts that hypertension, a modifiable vascular risk factor, may indeed be an independent predictor of late-onset epilepsy.”

There are “plausible mechanisms” that support both a direct, and indirect, role of hypertension – for example, through accumulation of small vessel disease in the brain – but further research will be necessary to elucidate the exact mechanisms involved in the process,” she added.
 

‘Welcome addition’

In a joint comment, Hedley C.A. Emsley, PhD, professor of clinical neuroscience, Lancaster (England) University, and Jasmine Wall, MBBChir, academic clinical fellow in neurology, Lancaster University, described the study as a “welcome addition to this field,” noting that the Framingham Heart Study “lends itself well to an embedded observational study of this nature of late-onset epilepsy.”

Dr. Emsley and Dr. Wall, who were not involved in the research, said that the “apparent magnitude of increased late-onset epilepsy risk association with hypertension in the Stefanidou et al study is quite striking,” even allowing for the “relatively small sample size,” since their analysis and findings appear to “withstand exclusion of individuals who became normotensive on antihypertensive treatment.”

They noted that in recent years there has been a growing body of evidence highlighting the importance of hypertension in late-onset epilepsy epileptogenesis with subclinical cerebrovascular diseases, including “otherwise occult cerebral small vessel disease believed to be a frequent cause.”

The mechanisms “remain unclear,” but they could potentially include diffuse cerebral microangiopathy, structural and physiological changes, and/or blood-brain barrier dysfunction and leakage, they suggested.

“Although there is no current consensus over an age threshold that defines ‘late onset,’ we would argue that age thresholds used in such studies of late-onset epilepsy should be lower, to avoid missing younger adults at risk through vascular mechanisms,” Dr. Emsley and Dr. Wall added.

The study authors suggest that “potential pathophysiologic mechanisms can further be explored in future experimental studies and clinical trials.”

This study was funded by grants from the National Institutes of Health and Finding a Cure for Epilepsy/Seizures. Dr. Stefanidou disclosed relevant financial relationships. Dr. Emsley and Dr. Wall disclosed no relevant financial relationships.

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

Hypertension is associated with more than a twofold increased risk of developing late-onset epilepsy even in patients who have not had a previous stroke, new research suggests.

After excluding individuals with normal blood pressure who were taking antihypertensive medication, investigators found hypertension was linked to an almost 2.5-fold higher risk of epilepsy.

“Our findings further expand upon our knowledge of the negative effects hypertension has on brain health and, regarding epilepsy, that effect may be starting even in midlife,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University.

“Practicing clinicians should be vigilant to diagnose hypertension, discuss with patients all potential long-term brain health outcomes, and need for treatment. Furthermore, in those presenting with new-onset epilepsy later in life, screening for potentially undiagnosed hypertension should be included in the initial workup,” she said.

The study was published online Nov. 17, 2021, in Epilepsia.
 

Unknown etiology

“New-onset epilepsy risk increases with increasing age over the age of 65 and can affect 15-20 per 1,000 older individuals. Although the most common causes for seizures in this age group are prior history of stroke and presence of dementia, for about 30%-40% of patients, the etiology of seizures remains unknown,” Dr. Stefanidou said.

“We wanted to study if modifiable vascular risk factors that are known to contribute both to vascular brain aging and to neurodegeneration may directly predict the development of epilepsy, even in the absence of clinical stroke or dementia,” she added.

To investigate, the researchers turned to data from participants in the Offspring Cohort of the Framingham Health Study (FHS). The original FHS was an ongoing longitudinal community-based study that first began in 1948. Offspring of the original cohort and their spouses (n = 5,124) were enrolled in the Offspring Cohort in 1971, with surveillance of these second-generation participants based on exam visits occurring every 4 years.

The study included participants who had attended exam 5 (1991-1995), were age 45 years or older, had available vascular risk factor (VRF) data, and available follow-up data on epilepsy status (n = 2,986; mean age, 58 years; 48% male).

The investigators conducted two statistical analyses. In the primary model, they adjusted for age and gender, while in a secondary model they also adjusted for prevalent and interim stroke. They also conducted an analysis that excluded participants treated with antihypertensive medication and had normal blood pressure.
 

Plausible mechanisms

During a mean follow-up of 19.2 years, 55 incident epilepsy cases were identified. The mean age of these patients was 73.8 years.

In the primary model, hypertension was associated with an almost twofold higher risk of developing epilepsy (hazard ratio, 1.97; 95% confidence interval, 1.13-3.45; P = .017).

Interestingly, the Framingham Stroke Risk Profile – a calculation based on an array of factors, including age/sex, systolic blood pressure, antihypertensive therapy, diabetes, history of cardiovascular disease, atrial fibrillation, and cigarette smoking – was not associated with incident epilepsy, and there was no other significant associated between any of the other VRFs when looked at independently.

When the researchers adjusted for prevalent and interim stroke, they continued to find an almost twofold higher risk of developing epilepsy (HR 1.93; 95% CI, 1.10-3.37; P = .022). An analysis that adjusted for competing risk of death obtained similar findings (HR, 1.98; 95% CI, 1.03-3.81; P = .042).

The model that excluded patients receiving antihypertensive treatment, whose blood pressure readings were normal (n = 2,162; 50 incident epilepsy cases) showed an even stronger association (HR, 2.44; 95% CI, 1.36-4.35; P = .003).

“Our results are based on an epidemiological, observational study, therefore our findings point to an association between hypertension and new-onset epilepsy later in life,” said Dr. Stefanidou.

She noted that because it was an observational study, “a cause-effect relationship cannot be established based on these results, but there is growing evidence from our, as well as other, similar cohorts that hypertension, a modifiable vascular risk factor, may indeed be an independent predictor of late-onset epilepsy.”

There are “plausible mechanisms” that support both a direct, and indirect, role of hypertension – for example, through accumulation of small vessel disease in the brain – but further research will be necessary to elucidate the exact mechanisms involved in the process,” she added.
 

‘Welcome addition’

In a joint comment, Hedley C.A. Emsley, PhD, professor of clinical neuroscience, Lancaster (England) University, and Jasmine Wall, MBBChir, academic clinical fellow in neurology, Lancaster University, described the study as a “welcome addition to this field,” noting that the Framingham Heart Study “lends itself well to an embedded observational study of this nature of late-onset epilepsy.”

Dr. Emsley and Dr. Wall, who were not involved in the research, said that the “apparent magnitude of increased late-onset epilepsy risk association with hypertension in the Stefanidou et al study is quite striking,” even allowing for the “relatively small sample size,” since their analysis and findings appear to “withstand exclusion of individuals who became normotensive on antihypertensive treatment.”

They noted that in recent years there has been a growing body of evidence highlighting the importance of hypertension in late-onset epilepsy epileptogenesis with subclinical cerebrovascular diseases, including “otherwise occult cerebral small vessel disease believed to be a frequent cause.”

The mechanisms “remain unclear,” but they could potentially include diffuse cerebral microangiopathy, structural and physiological changes, and/or blood-brain barrier dysfunction and leakage, they suggested.

“Although there is no current consensus over an age threshold that defines ‘late onset,’ we would argue that age thresholds used in such studies of late-onset epilepsy should be lower, to avoid missing younger adults at risk through vascular mechanisms,” Dr. Emsley and Dr. Wall added.

The study authors suggest that “potential pathophysiologic mechanisms can further be explored in future experimental studies and clinical trials.”

This study was funded by grants from the National Institutes of Health and Finding a Cure for Epilepsy/Seizures. Dr. Stefanidou disclosed relevant financial relationships. Dr. Emsley and Dr. Wall disclosed no relevant financial relationships.

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

A newly released position statement from the American Academy of Neurology (AAN) provides guidance to neurologists about counseling  patients with Alzheimer’s disease and their families about the controversial drug aducanumab (Aduhelm).

The statement includes ethical considerations and recommendations for informed consent, and the AAN notes that neurologists should ensure that patients understand all of the issues and uncertainties surrounding the use of aducanumab.

“Neurologists and other clinicians want to provide the best care to patients and families, particularly for a disease that is as challenging as Alzheimer’s. We hope that this statement can be a guide for clinicians in communicating with patients and families in order to carefully consider decisions about the use of aducanumab,” said lead author Winston Chiong, MD, PhD, University of California San Francisco Memory and Aging Center, and a member of the AAN’s Ethics, Law, and Humanities Committee.

The statement was published online Nov. 17 in Neurology.
 

Open, honest communication

The Food and Drug Administration approved the antiamyloid agent aducanumab based on two studies that were both stopped prematurely for futility. In subsequent post hoc analyses of the available data, one of those studies indicated a statistically significant, albeit small, benefit with high-dose aducanumab, while the other study continued to show no benefit.

The clinical importance of the small statistical benefit in the single trial for daily function is unclear, and aducanumab was also associated with brain inflammation and brain bleeds in more than one-third of patients who received the FDA-approved dose, which requires regular brain MRI monitoring.

All of this should be communicated to patients, the AAN advises.

Patients should know that while aducanumab reduces beta-amyloid plaques in the brain that are markers of Alzheimer’s disease, it remains unclear whether this provides any meaningful benefit.

The AAN adds that it is equally important to tell patients and families that aducanumab does not restore cognitive function and that there is insufficient data to offer it to people with moderate or advanced dementia or to those without evidence of beta-amyloid plaques.

It’s important to note that very few participants in the aducanumab trials were Hispanic, Black, or Indigenous. 

“Informed consent conversations with patients of populations underrepresented in clinical trials should include disclosure about the absence of safety and efficacy data in these groups,” the authors noted.
 

‘New territory’ for neurologists

“There are two aspects of aducanumab that are relatively new territory for us as neurologists,” Dr. Chiong said. One is the controversy about the evidence for the drug. “In the statement, we’ve tried to help clinicians communicate the uncertainty over aducanumab’s risks and potential benefits,” Dr. Chiong said. The other is the high cost of the drug and how it will be covered.

Aducanumab has a price tag of $56,000 per year, which does not include the cost of infusing the drug, required repeat imaging, and medical management.

The AAN estimates annual costs of prescribing aducanumab may top $100,000 per year. With Medicare generally covering 80%, patients and families must be told that the full costs of treatment may not be covered.

“Regarding cost, we probably don’t think often enough about what prescribing a drug means for an individual patient’s finances and for the health system,” said Dr. Chiong. “In particular, when patients are in Medicare we might assume their health care costs will be sufficiently covered, but because aducanumab is so expensive its use is likely to impose very significant costs on individual patients as well as to the Medicare program,” Dr. Chiong said.

“It is understandable why a new drug for Alzheimer’s disease generates so much interest, because while its approval has been controversial, it still offers a glimmer of hope to patients and their families,” AAN President Orly Avitzur, MD, said in a news release. “By using ethical principles to create this position statement, the American Academy of Neurology aims to help neurologists and other physicians transparently counsel patients and their families with a goal of providing the highest quality patient-centered care,” Dr. Avitzur said.

This statement was approved by the Ethics, Law, and Humanities Committee, a joint committee of the AAN, American Neurological Association, and Child Neurology Society.

This research had no targeted funding. Dr. Chiong has received personal compensation for serving on the Neuroethics Working Group of the National Institutes of Health BRAIN Initiative, and his institution has received research support from the National Institutes of Health. A complete list of author disclosures is available with the original article.

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

A newly released position statement from the American Academy of Neurology (AAN) provides guidance to neurologists about counseling  patients with Alzheimer’s disease and their families about the controversial drug aducanumab (Aduhelm).

The statement includes ethical considerations and recommendations for informed consent, and the AAN notes that neurologists should ensure that patients understand all of the issues and uncertainties surrounding the use of aducanumab.

“Neurologists and other clinicians want to provide the best care to patients and families, particularly for a disease that is as challenging as Alzheimer’s. We hope that this statement can be a guide for clinicians in communicating with patients and families in order to carefully consider decisions about the use of aducanumab,” said lead author Winston Chiong, MD, PhD, University of California San Francisco Memory and Aging Center, and a member of the AAN’s Ethics, Law, and Humanities Committee.

The statement was published online Nov. 17 in Neurology.
 

Open, honest communication

The Food and Drug Administration approved the antiamyloid agent aducanumab based on two studies that were both stopped prematurely for futility. In subsequent post hoc analyses of the available data, one of those studies indicated a statistically significant, albeit small, benefit with high-dose aducanumab, while the other study continued to show no benefit.

The clinical importance of the small statistical benefit in the single trial for daily function is unclear, and aducanumab was also associated with brain inflammation and brain bleeds in more than one-third of patients who received the FDA-approved dose, which requires regular brain MRI monitoring.

All of this should be communicated to patients, the AAN advises.

Patients should know that while aducanumab reduces beta-amyloid plaques in the brain that are markers of Alzheimer’s disease, it remains unclear whether this provides any meaningful benefit.

The AAN adds that it is equally important to tell patients and families that aducanumab does not restore cognitive function and that there is insufficient data to offer it to people with moderate or advanced dementia or to those without evidence of beta-amyloid plaques.

It’s important to note that very few participants in the aducanumab trials were Hispanic, Black, or Indigenous. 

“Informed consent conversations with patients of populations underrepresented in clinical trials should include disclosure about the absence of safety and efficacy data in these groups,” the authors noted.
 

‘New territory’ for neurologists

“There are two aspects of aducanumab that are relatively new territory for us as neurologists,” Dr. Chiong said. One is the controversy about the evidence for the drug. “In the statement, we’ve tried to help clinicians communicate the uncertainty over aducanumab’s risks and potential benefits,” Dr. Chiong said. The other is the high cost of the drug and how it will be covered.

Aducanumab has a price tag of $56,000 per year, which does not include the cost of infusing the drug, required repeat imaging, and medical management.

The AAN estimates annual costs of prescribing aducanumab may top $100,000 per year. With Medicare generally covering 80%, patients and families must be told that the full costs of treatment may not be covered.

“Regarding cost, we probably don’t think often enough about what prescribing a drug means for an individual patient’s finances and for the health system,” said Dr. Chiong. “In particular, when patients are in Medicare we might assume their health care costs will be sufficiently covered, but because aducanumab is so expensive its use is likely to impose very significant costs on individual patients as well as to the Medicare program,” Dr. Chiong said.

“It is understandable why a new drug for Alzheimer’s disease generates so much interest, because while its approval has been controversial, it still offers a glimmer of hope to patients and their families,” AAN President Orly Avitzur, MD, said in a news release. “By using ethical principles to create this position statement, the American Academy of Neurology aims to help neurologists and other physicians transparently counsel patients and their families with a goal of providing the highest quality patient-centered care,” Dr. Avitzur said.

This statement was approved by the Ethics, Law, and Humanities Committee, a joint committee of the AAN, American Neurological Association, and Child Neurology Society.

This research had no targeted funding. Dr. Chiong has received personal compensation for serving on the Neuroethics Working Group of the National Institutes of Health BRAIN Initiative, and his institution has received research support from the National Institutes of Health. A complete list of author disclosures is available with the original article.

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

A newly released position statement from the American Academy of Neurology (AAN) provides guidance to neurologists about counseling  patients with Alzheimer’s disease and their families about the controversial drug aducanumab (Aduhelm).

The statement includes ethical considerations and recommendations for informed consent, and the AAN notes that neurologists should ensure that patients understand all of the issues and uncertainties surrounding the use of aducanumab.

“Neurologists and other clinicians want to provide the best care to patients and families, particularly for a disease that is as challenging as Alzheimer’s. We hope that this statement can be a guide for clinicians in communicating with patients and families in order to carefully consider decisions about the use of aducanumab,” said lead author Winston Chiong, MD, PhD, University of California San Francisco Memory and Aging Center, and a member of the AAN’s Ethics, Law, and Humanities Committee.

The statement was published online Nov. 17 in Neurology.
 

Open, honest communication

The Food and Drug Administration approved the antiamyloid agent aducanumab based on two studies that were both stopped prematurely for futility. In subsequent post hoc analyses of the available data, one of those studies indicated a statistically significant, albeit small, benefit with high-dose aducanumab, while the other study continued to show no benefit.

The clinical importance of the small statistical benefit in the single trial for daily function is unclear, and aducanumab was also associated with brain inflammation and brain bleeds in more than one-third of patients who received the FDA-approved dose, which requires regular brain MRI monitoring.

All of this should be communicated to patients, the AAN advises.

Patients should know that while aducanumab reduces beta-amyloid plaques in the brain that are markers of Alzheimer’s disease, it remains unclear whether this provides any meaningful benefit.

The AAN adds that it is equally important to tell patients and families that aducanumab does not restore cognitive function and that there is insufficient data to offer it to people with moderate or advanced dementia or to those without evidence of beta-amyloid plaques.

It’s important to note that very few participants in the aducanumab trials were Hispanic, Black, or Indigenous. 

“Informed consent conversations with patients of populations underrepresented in clinical trials should include disclosure about the absence of safety and efficacy data in these groups,” the authors noted.
 

‘New territory’ for neurologists

“There are two aspects of aducanumab that are relatively new territory for us as neurologists,” Dr. Chiong said. One is the controversy about the evidence for the drug. “In the statement, we’ve tried to help clinicians communicate the uncertainty over aducanumab’s risks and potential benefits,” Dr. Chiong said. The other is the high cost of the drug and how it will be covered.

Aducanumab has a price tag of $56,000 per year, which does not include the cost of infusing the drug, required repeat imaging, and medical management.

The AAN estimates annual costs of prescribing aducanumab may top $100,000 per year. With Medicare generally covering 80%, patients and families must be told that the full costs of treatment may not be covered.

“Regarding cost, we probably don’t think often enough about what prescribing a drug means for an individual patient’s finances and for the health system,” said Dr. Chiong. “In particular, when patients are in Medicare we might assume their health care costs will be sufficiently covered, but because aducanumab is so expensive its use is likely to impose very significant costs on individual patients as well as to the Medicare program,” Dr. Chiong said.

“It is understandable why a new drug for Alzheimer’s disease generates so much interest, because while its approval has been controversial, it still offers a glimmer of hope to patients and their families,” AAN President Orly Avitzur, MD, said in a news release. “By using ethical principles to create this position statement, the American Academy of Neurology aims to help neurologists and other physicians transparently counsel patients and their families with a goal of providing the highest quality patient-centered care,” Dr. Avitzur said.

This statement was approved by the Ethics, Law, and Humanities Committee, a joint committee of the AAN, American Neurological Association, and Child Neurology Society.

This research had no targeted funding. Dr. Chiong has received personal compensation for serving on the Neuroethics Working Group of the National Institutes of Health BRAIN Initiative, and his institution has received research support from the National Institutes of Health. A complete list of author disclosures is available with the original article.

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

LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.

Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.

“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”

To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.

After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.

CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.

Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.

“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”

Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.

“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”

Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.

“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”

The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.

“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”

The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.

LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.

Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.

“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”

To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.

After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.

CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.

Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.

“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”

Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.

“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”

Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.

“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”

The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.

“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”

The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.

LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.

Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.

“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”

To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.

After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.

CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.

Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.

“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”

Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.

“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”

Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.

“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”

The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.

“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”

The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.

Erenumab, a calcitonin-gene related peptide receptor (CGRP) inhibitor, is more tolerable and effective than topiramate for treating patients with migraine, according to data from almost 800 patients in the first head-to-head trial of its kind.

The findings suggest that erenumab may help overcome longstanding issues with migraine medication adherence, and additional supportive data may alter treatment sequencing, reported lead author Uwe Reuter, MD, professor at Charité Universitätsmedizin Berlin, and colleagues.

“So far, no study has been done in order to compare the efficacy of a monoclonal antibody targeting the CGRP pathway to that of a standard of care oral preventive drug,” the investigators wrote in Cephalalgia.

The phase 4 HER-MES trial aimed to address this knowledge gap by enrolling 777 adult patients with a history of migraine. All patients reported migraine with or without aura for at least 1 year prior to screening. At baseline, most patients (65%) reported 8-14 migraine days per months, followed by 4-7 days (24.0%), and at least 15 days (11.0%). No patients had previously received topiramate or a CGRP-targeting agent.

“HER-MES includes a broad migraine population with two-thirds of the patients in the high-frequency migraine spectrum,” the investigators noted. “Despite a mean disease duration of about 20 years, almost 60% of the patients had not received previous prophylactic treatment, which underlines the long-standing problem of undertreatment in migraine.”

The trial had a double-dummy design; patients were randomized in a 1:1 ratio to receive either subcutaneous erenumab (70 or 140 mg/month) plus oral placebo, or oral topiramate (50-100 mg/day) plus subcutaneous placebo. The topiramate dose was uptitrated over the first 6 weeks. Treatments were given for a total of 24 weeks or until discontinuation due to adverse events, which was the primary endpoint. The secondary endpoint was efficacy over months 4-6, defined as at least 50% reduction in monthly migraine days, compared with baseline. Other patient-reported outcomes were also evaluated.

After 24 weeks, 95.1% of patients were still enrolled in the trial. Discontinuations due to adverse events were almost four times as common in the topiramate group than the erenumab group (38.9% vs. 10.6%; odds ratio [OR], 0.19; confidence interval, 0.13-0.27; P less than .001). Efficacy findings followed suit, with 55.4% of patients in the erenumab group reporting at least 50% reduction in monthly migraine days, compared with 31.2% of patients in the topiramate group (OR, 2.76; 95% CI, 2.06-3.71; P less than.001).

Erenumab significantly improved monthly migraine days, headache impact test (HIT-6) scores, and short form health survey version (SF-35v2) scores, including physical and mental components (P less than .001 for all).

Safety profiles aligned with previous findings.

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy,” the investigators concluded. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden, and improving quality of life in a broad migraine population.”
 

Superior tolerability

Commenting on the study, Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, said this is “a very important, very well conducted trial that documents what many of us already suspected; erenumab clearly has better tolerability than topiramate as well as better efficacy.”

Dr. Rapoport, a past president of the International Headache Society, said the study highlights an area of unmet need in neurology practice.

“Despite most patients in the trial having chronic headaches for 20 years, 60% of them had never received preventive treatment,” he said, noting that this reflects current practice in the United States.

Dr. Rapoport said primary care providers in the United States prescribe preventive migraine medications to 10%-15% of eligible patients. Prescribing rates for general neurologists are slightly higher, he said, ranging from 35% to 40%, while headache specialists prescribe 70%-90% of the time.

“How can we improve this situation?” Dr. Rapoport asked. “For years we have tried to improve it with education, but we need to do a better job. We need to educate our primary care physicians in more practical ways. We have to teach them how to make a diagnosis of high frequency migraine and chronic migraine and strongly suggest that those patients be put on appropriate preventive medications.”

Barriers to care may be systemic, according to Dr. Rapoport.

“One issue in the U.S. is that patients with commercial insurance are almost always required to fail two or three categories of older oral preventive migraine medications before they can get a monoclonal antibody or gepants for prevention,” he said. “It would be good if we could change that system so that patients that absolutely need the better tolerated, more effective preventive medications could get them sooner rather than later. This will help them feel and function better, with less pain, and eventually bring down the cost of migraine therapy.”

While Dr. Reuter and colleagues concluded that revised treatment sequencing may be warranted after more trials show similar results, Dr. Rapoport suggested that “this was such a large, well-performed, 6-month study with few dropouts, that further trials to confirm these findings are unnecessary, in my opinion.”

The HER-MES trial was funded by Novartis. Dr. Reuter and colleagues disclosed additional relationships with Eli Lilly, Teva Pharmaceutical, Allergan, and others. Dr. Rapoport was involved in early topiramate trials for prevention and migraine, and is a speaker for Amgen.

Erenumab, a calcitonin-gene related peptide receptor (CGRP) inhibitor, is more tolerable and effective than topiramate for treating patients with migraine, according to data from almost 800 patients in the first head-to-head trial of its kind.

The findings suggest that erenumab may help overcome longstanding issues with migraine medication adherence, and additional supportive data may alter treatment sequencing, reported lead author Uwe Reuter, MD, professor at Charité Universitätsmedizin Berlin, and colleagues.

“So far, no study has been done in order to compare the efficacy of a monoclonal antibody targeting the CGRP pathway to that of a standard of care oral preventive drug,” the investigators wrote in Cephalalgia.

The phase 4 HER-MES trial aimed to address this knowledge gap by enrolling 777 adult patients with a history of migraine. All patients reported migraine with or without aura for at least 1 year prior to screening. At baseline, most patients (65%) reported 8-14 migraine days per months, followed by 4-7 days (24.0%), and at least 15 days (11.0%). No patients had previously received topiramate or a CGRP-targeting agent.

“HER-MES includes a broad migraine population with two-thirds of the patients in the high-frequency migraine spectrum,” the investigators noted. “Despite a mean disease duration of about 20 years, almost 60% of the patients had not received previous prophylactic treatment, which underlines the long-standing problem of undertreatment in migraine.”

The trial had a double-dummy design; patients were randomized in a 1:1 ratio to receive either subcutaneous erenumab (70 or 140 mg/month) plus oral placebo, or oral topiramate (50-100 mg/day) plus subcutaneous placebo. The topiramate dose was uptitrated over the first 6 weeks. Treatments were given for a total of 24 weeks or until discontinuation due to adverse events, which was the primary endpoint. The secondary endpoint was efficacy over months 4-6, defined as at least 50% reduction in monthly migraine days, compared with baseline. Other patient-reported outcomes were also evaluated.

After 24 weeks, 95.1% of patients were still enrolled in the trial. Discontinuations due to adverse events were almost four times as common in the topiramate group than the erenumab group (38.9% vs. 10.6%; odds ratio [OR], 0.19; confidence interval, 0.13-0.27; P less than .001). Efficacy findings followed suit, with 55.4% of patients in the erenumab group reporting at least 50% reduction in monthly migraine days, compared with 31.2% of patients in the topiramate group (OR, 2.76; 95% CI, 2.06-3.71; P less than.001).

Erenumab significantly improved monthly migraine days, headache impact test (HIT-6) scores, and short form health survey version (SF-35v2) scores, including physical and mental components (P less than .001 for all).

Safety profiles aligned with previous findings.

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy,” the investigators concluded. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden, and improving quality of life in a broad migraine population.”
 

Superior tolerability

Commenting on the study, Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, said this is “a very important, very well conducted trial that documents what many of us already suspected; erenumab clearly has better tolerability than topiramate as well as better efficacy.”

Dr. Rapoport, a past president of the International Headache Society, said the study highlights an area of unmet need in neurology practice.

“Despite most patients in the trial having chronic headaches for 20 years, 60% of them had never received preventive treatment,” he said, noting that this reflects current practice in the United States.

Dr. Rapoport said primary care providers in the United States prescribe preventive migraine medications to 10%-15% of eligible patients. Prescribing rates for general neurologists are slightly higher, he said, ranging from 35% to 40%, while headache specialists prescribe 70%-90% of the time.

“How can we improve this situation?” Dr. Rapoport asked. “For years we have tried to improve it with education, but we need to do a better job. We need to educate our primary care physicians in more practical ways. We have to teach them how to make a diagnosis of high frequency migraine and chronic migraine and strongly suggest that those patients be put on appropriate preventive medications.”

Barriers to care may be systemic, according to Dr. Rapoport.

“One issue in the U.S. is that patients with commercial insurance are almost always required to fail two or three categories of older oral preventive migraine medications before they can get a monoclonal antibody or gepants for prevention,” he said. “It would be good if we could change that system so that patients that absolutely need the better tolerated, more effective preventive medications could get them sooner rather than later. This will help them feel and function better, with less pain, and eventually bring down the cost of migraine therapy.”

While Dr. Reuter and colleagues concluded that revised treatment sequencing may be warranted after more trials show similar results, Dr. Rapoport suggested that “this was such a large, well-performed, 6-month study with few dropouts, that further trials to confirm these findings are unnecessary, in my opinion.”

The HER-MES trial was funded by Novartis. Dr. Reuter and colleagues disclosed additional relationships with Eli Lilly, Teva Pharmaceutical, Allergan, and others. Dr. Rapoport was involved in early topiramate trials for prevention and migraine, and is a speaker for Amgen.

Erenumab, a calcitonin-gene related peptide receptor (CGRP) inhibitor, is more tolerable and effective than topiramate for treating patients with migraine, according to data from almost 800 patients in the first head-to-head trial of its kind.

The findings suggest that erenumab may help overcome longstanding issues with migraine medication adherence, and additional supportive data may alter treatment sequencing, reported lead author Uwe Reuter, MD, professor at Charité Universitätsmedizin Berlin, and colleagues.

“So far, no study has been done in order to compare the efficacy of a monoclonal antibody targeting the CGRP pathway to that of a standard of care oral preventive drug,” the investigators wrote in Cephalalgia.

The phase 4 HER-MES trial aimed to address this knowledge gap by enrolling 777 adult patients with a history of migraine. All patients reported migraine with or without aura for at least 1 year prior to screening. At baseline, most patients (65%) reported 8-14 migraine days per months, followed by 4-7 days (24.0%), and at least 15 days (11.0%). No patients had previously received topiramate or a CGRP-targeting agent.

“HER-MES includes a broad migraine population with two-thirds of the patients in the high-frequency migraine spectrum,” the investigators noted. “Despite a mean disease duration of about 20 years, almost 60% of the patients had not received previous prophylactic treatment, which underlines the long-standing problem of undertreatment in migraine.”

The trial had a double-dummy design; patients were randomized in a 1:1 ratio to receive either subcutaneous erenumab (70 or 140 mg/month) plus oral placebo, or oral topiramate (50-100 mg/day) plus subcutaneous placebo. The topiramate dose was uptitrated over the first 6 weeks. Treatments were given for a total of 24 weeks or until discontinuation due to adverse events, which was the primary endpoint. The secondary endpoint was efficacy over months 4-6, defined as at least 50% reduction in monthly migraine days, compared with baseline. Other patient-reported outcomes were also evaluated.

After 24 weeks, 95.1% of patients were still enrolled in the trial. Discontinuations due to adverse events were almost four times as common in the topiramate group than the erenumab group (38.9% vs. 10.6%; odds ratio [OR], 0.19; confidence interval, 0.13-0.27; P less than .001). Efficacy findings followed suit, with 55.4% of patients in the erenumab group reporting at least 50% reduction in monthly migraine days, compared with 31.2% of patients in the topiramate group (OR, 2.76; 95% CI, 2.06-3.71; P less than.001).

Erenumab significantly improved monthly migraine days, headache impact test (HIT-6) scores, and short form health survey version (SF-35v2) scores, including physical and mental components (P less than .001 for all).

Safety profiles aligned with previous findings.

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy,” the investigators concluded. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden, and improving quality of life in a broad migraine population.”
 

Superior tolerability

Commenting on the study, Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, said this is “a very important, very well conducted trial that documents what many of us already suspected; erenumab clearly has better tolerability than topiramate as well as better efficacy.”

Dr. Rapoport, a past president of the International Headache Society, said the study highlights an area of unmet need in neurology practice.

“Despite most patients in the trial having chronic headaches for 20 years, 60% of them had never received preventive treatment,” he said, noting that this reflects current practice in the United States.

Dr. Rapoport said primary care providers in the United States prescribe preventive migraine medications to 10%-15% of eligible patients. Prescribing rates for general neurologists are slightly higher, he said, ranging from 35% to 40%, while headache specialists prescribe 70%-90% of the time.

“How can we improve this situation?” Dr. Rapoport asked. “For years we have tried to improve it with education, but we need to do a better job. We need to educate our primary care physicians in more practical ways. We have to teach them how to make a diagnosis of high frequency migraine and chronic migraine and strongly suggest that those patients be put on appropriate preventive medications.”

Barriers to care may be systemic, according to Dr. Rapoport.

“One issue in the U.S. is that patients with commercial insurance are almost always required to fail two or three categories of older oral preventive migraine medications before they can get a monoclonal antibody or gepants for prevention,” he said. “It would be good if we could change that system so that patients that absolutely need the better tolerated, more effective preventive medications could get them sooner rather than later. This will help them feel and function better, with less pain, and eventually bring down the cost of migraine therapy.”

While Dr. Reuter and colleagues concluded that revised treatment sequencing may be warranted after more trials show similar results, Dr. Rapoport suggested that “this was such a large, well-performed, 6-month study with few dropouts, that further trials to confirm these findings are unnecessary, in my opinion.”

The HER-MES trial was funded by Novartis. Dr. Reuter and colleagues disclosed additional relationships with Eli Lilly, Teva Pharmaceutical, Allergan, and others. Dr. Rapoport was involved in early topiramate trials for prevention and migraine, and is a speaker for Amgen.

Most cases of new daily persistent headache (NDPH) are moderate to severe and many feature characteristics often associated with migraine, according to a new retrospective chart review.

“Future prospective studies are needed to better understand this disabling disorder,” wrote Randolph W. Evans, MD, of Baylor College of Medicine of Houston, and Dana P. Turner, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston. Their study was published Oct. 28 in Headache.

To categorize the infrequently reported clinical features of NDPH, the researchers launched a retrospective study of patients who were provisionally diagnosed with NDPH by Dr. Evans at an outpatient clinic in Houston from Sept. 1, 2011, to Feb. 28, 2020. Of the 328 patients whose diagnosis ultimately matched the ICHD-3 criteria, the average age at onset was 40.3 years (range 12-87 years). Approximately 70% were White, and nearly 66% were women. Two hundred and sixty were diagnosed with the migraine phenotype and 68 were diagnosed with the tension-type phenotype.
 

Key features

The median duration of NDPH at the time of the initial consult with Dr. Evans was 0.7 years, and it was 1.9 years at the time of the last visit. Almost 33% of patients with the migraine phenotype had a history of episodic migraine compared with 16.2% with the tension-type phenotype. Headaches were side-locked unilateral in 8.5% (n = 28) of all patients, and 3.6% (n = 12) had a thunderclap onset.

The most common clinical features across all patients included noise sensitivity (72.1%), light sensitivity (71%), moderate pain at the time of initial consult (57.9%), pressure pain (54.9%), and throbbing pain (50.9%). Nausea was reported in 157 patients and vomiting was reported in 48 patients, all of whom were in the migraine phenotype group. Thunderclap onset was far more prevalent in the migraine phenotype group (11 patients) compared with the tension-type phenotype group (1 patient), as was vertigo (19 patients compared with 1) and visual aura (21 compared with 0).

The top precipitating factors across all patients included stressful life events (20.4%), an antecedent upper respiratory infection or flu-like illness (10.1%), and antecedent extracranial surgery (1.5%). Exacerbating or aggravating factors were far more prevalent in the migraine phenotype group compared with the tension-type phenotype group, with stress (14.6% vs. 5.9%), bright or flashing light (10.4% vs. 1.5%), loud noise (8.5% vs. 0%), and lack of sleep (6.5% vs. 4.4%) leading the way.

The months with the most onsets were June (8.5%), January (7.6%), and February (7.6%); there was no clear seasonal or cyclical variation. The most common prognostic type across all patients was persisting (refractory) at 93%, followed by remitting (self-limiting) at 4.3% and relapsing-remitting at 2.7%.
 

Unlocking a medical mystery

“This is the largest case review study ever published on NDPH, especially because most people think it’s a fairly rare disorder when it’s actually not,” Herbert G. Markley, MD, of the New England Regional Headache Center in Worcester, Mass., said in an interview.

“The thing people need to understand is that they may have a lot of these patients in their practice and not realize it,” he added. “They keep trying one medication after another, and the patients are giving up, and the doctors are giving up. It’s terrible. We don’t know what causes it, and we don’t know how to treat it. It’s one of the biggest mysteries left in medical science.”

“My idea about this condition, and this is shared by others, is that NDPH is not a diagnosis that describes a cohesive group of patients but rather a group of people who share certain features,” Morris Levin, MD, director of the Headache Center at the University of California, San Francisco, said in an interview. “And they would be better served if this diagnosis was split into different categories.”

While praising Dr. Evans and Dr. Turner for their categorization and classification work, Dr. Levin asked, “Let’s say you diagnose someone with NDPH; does that in any way help you with management of this person? The answer is no. Some might say, ‘If you put the patients in the migraine phenotype group, then you can use migraine treatments.’ My point would be: then call it migraine.

“I believe another way to approach NDPH might be to create subcategories of migraine and tension-type headaches,” he added. “A migraine that is either intermittent or nonexistent suddenly becomes daily. That could be a subcategory; rather than being called NDPH, call it ‘new persistent chronic migraine.’ Or ‘new persistent chronic tension-type headache.’ Perhaps that would serve us better in terms of grasping the underlying mechanisms and the best treatment for these patients.”

Along the same lines, Dr. Markley echoed Dr. Evans’ call for more prospective studies and more research on possible medication, hoping to fuel further understanding of this debilitating disorder.

“I think this will be a landmark study for people to look back on,” he said, “especially for anyone going into the headache specialty who has never heard of this type of headache and keeps wondering why they can’t help certain patients, no matter how many medications they try.”

The authors acknowledged their study’s limitations, including its single-center nature and the data abstraction process being performed by just one person. They added, however, that Dr. Evans is a “very experienced researcher with more than 30 years of experience in headache medicine who was abstracting his own patients, data that were very familiar to him.”

Dr. Evans and Dr. Turner declared no potential conflicts of interest.

Most cases of new daily persistent headache (NDPH) are moderate to severe and many feature characteristics often associated with migraine, according to a new retrospective chart review.

“Future prospective studies are needed to better understand this disabling disorder,” wrote Randolph W. Evans, MD, of Baylor College of Medicine of Houston, and Dana P. Turner, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston. Their study was published Oct. 28 in Headache.

To categorize the infrequently reported clinical features of NDPH, the researchers launched a retrospective study of patients who were provisionally diagnosed with NDPH by Dr. Evans at an outpatient clinic in Houston from Sept. 1, 2011, to Feb. 28, 2020. Of the 328 patients whose diagnosis ultimately matched the ICHD-3 criteria, the average age at onset was 40.3 years (range 12-87 years). Approximately 70% were White, and nearly 66% were women. Two hundred and sixty were diagnosed with the migraine phenotype and 68 were diagnosed with the tension-type phenotype.
 

Key features

The median duration of NDPH at the time of the initial consult with Dr. Evans was 0.7 years, and it was 1.9 years at the time of the last visit. Almost 33% of patients with the migraine phenotype had a history of episodic migraine compared with 16.2% with the tension-type phenotype. Headaches were side-locked unilateral in 8.5% (n = 28) of all patients, and 3.6% (n = 12) had a thunderclap onset.

The most common clinical features across all patients included noise sensitivity (72.1%), light sensitivity (71%), moderate pain at the time of initial consult (57.9%), pressure pain (54.9%), and throbbing pain (50.9%). Nausea was reported in 157 patients and vomiting was reported in 48 patients, all of whom were in the migraine phenotype group. Thunderclap onset was far more prevalent in the migraine phenotype group (11 patients) compared with the tension-type phenotype group (1 patient), as was vertigo (19 patients compared with 1) and visual aura (21 compared with 0).

The top precipitating factors across all patients included stressful life events (20.4%), an antecedent upper respiratory infection or flu-like illness (10.1%), and antecedent extracranial surgery (1.5%). Exacerbating or aggravating factors were far more prevalent in the migraine phenotype group compared with the tension-type phenotype group, with stress (14.6% vs. 5.9%), bright or flashing light (10.4% vs. 1.5%), loud noise (8.5% vs. 0%), and lack of sleep (6.5% vs. 4.4%) leading the way.

The months with the most onsets were June (8.5%), January (7.6%), and February (7.6%); there was no clear seasonal or cyclical variation. The most common prognostic type across all patients was persisting (refractory) at 93%, followed by remitting (self-limiting) at 4.3% and relapsing-remitting at 2.7%.
 

Unlocking a medical mystery

“This is the largest case review study ever published on NDPH, especially because most people think it’s a fairly rare disorder when it’s actually not,” Herbert G. Markley, MD, of the New England Regional Headache Center in Worcester, Mass., said in an interview.

“The thing people need to understand is that they may have a lot of these patients in their practice and not realize it,” he added. “They keep trying one medication after another, and the patients are giving up, and the doctors are giving up. It’s terrible. We don’t know what causes it, and we don’t know how to treat it. It’s one of the biggest mysteries left in medical science.”

“My idea about this condition, and this is shared by others, is that NDPH is not a diagnosis that describes a cohesive group of patients but rather a group of people who share certain features,” Morris Levin, MD, director of the Headache Center at the University of California, San Francisco, said in an interview. “And they would be better served if this diagnosis was split into different categories.”

While praising Dr. Evans and Dr. Turner for their categorization and classification work, Dr. Levin asked, “Let’s say you diagnose someone with NDPH; does that in any way help you with management of this person? The answer is no. Some might say, ‘If you put the patients in the migraine phenotype group, then you can use migraine treatments.’ My point would be: then call it migraine.

“I believe another way to approach NDPH might be to create subcategories of migraine and tension-type headaches,” he added. “A migraine that is either intermittent or nonexistent suddenly becomes daily. That could be a subcategory; rather than being called NDPH, call it ‘new persistent chronic migraine.’ Or ‘new persistent chronic tension-type headache.’ Perhaps that would serve us better in terms of grasping the underlying mechanisms and the best treatment for these patients.”

Along the same lines, Dr. Markley echoed Dr. Evans’ call for more prospective studies and more research on possible medication, hoping to fuel further understanding of this debilitating disorder.

“I think this will be a landmark study for people to look back on,” he said, “especially for anyone going into the headache specialty who has never heard of this type of headache and keeps wondering why they can’t help certain patients, no matter how many medications they try.”

The authors acknowledged their study’s limitations, including its single-center nature and the data abstraction process being performed by just one person. They added, however, that Dr. Evans is a “very experienced researcher with more than 30 years of experience in headache medicine who was abstracting his own patients, data that were very familiar to him.”

Dr. Evans and Dr. Turner declared no potential conflicts of interest.

Most cases of new daily persistent headache (NDPH) are moderate to severe and many feature characteristics often associated with migraine, according to a new retrospective chart review.

“Future prospective studies are needed to better understand this disabling disorder,” wrote Randolph W. Evans, MD, of Baylor College of Medicine of Houston, and Dana P. Turner, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston. Their study was published Oct. 28 in Headache.

To categorize the infrequently reported clinical features of NDPH, the researchers launched a retrospective study of patients who were provisionally diagnosed with NDPH by Dr. Evans at an outpatient clinic in Houston from Sept. 1, 2011, to Feb. 28, 2020. Of the 328 patients whose diagnosis ultimately matched the ICHD-3 criteria, the average age at onset was 40.3 years (range 12-87 years). Approximately 70% were White, and nearly 66% were women. Two hundred and sixty were diagnosed with the migraine phenotype and 68 were diagnosed with the tension-type phenotype.
 

Key features

The median duration of NDPH at the time of the initial consult with Dr. Evans was 0.7 years, and it was 1.9 years at the time of the last visit. Almost 33% of patients with the migraine phenotype had a history of episodic migraine compared with 16.2% with the tension-type phenotype. Headaches were side-locked unilateral in 8.5% (n = 28) of all patients, and 3.6% (n = 12) had a thunderclap onset.

The most common clinical features across all patients included noise sensitivity (72.1%), light sensitivity (71%), moderate pain at the time of initial consult (57.9%), pressure pain (54.9%), and throbbing pain (50.9%). Nausea was reported in 157 patients and vomiting was reported in 48 patients, all of whom were in the migraine phenotype group. Thunderclap onset was far more prevalent in the migraine phenotype group (11 patients) compared with the tension-type phenotype group (1 patient), as was vertigo (19 patients compared with 1) and visual aura (21 compared with 0).

The top precipitating factors across all patients included stressful life events (20.4%), an antecedent upper respiratory infection or flu-like illness (10.1%), and antecedent extracranial surgery (1.5%). Exacerbating or aggravating factors were far more prevalent in the migraine phenotype group compared with the tension-type phenotype group, with stress (14.6% vs. 5.9%), bright or flashing light (10.4% vs. 1.5%), loud noise (8.5% vs. 0%), and lack of sleep (6.5% vs. 4.4%) leading the way.

The months with the most onsets were June (8.5%), January (7.6%), and February (7.6%); there was no clear seasonal or cyclical variation. The most common prognostic type across all patients was persisting (refractory) at 93%, followed by remitting (self-limiting) at 4.3% and relapsing-remitting at 2.7%.
 

Unlocking a medical mystery

“This is the largest case review study ever published on NDPH, especially because most people think it’s a fairly rare disorder when it’s actually not,” Herbert G. Markley, MD, of the New England Regional Headache Center in Worcester, Mass., said in an interview.

“The thing people need to understand is that they may have a lot of these patients in their practice and not realize it,” he added. “They keep trying one medication after another, and the patients are giving up, and the doctors are giving up. It’s terrible. We don’t know what causes it, and we don’t know how to treat it. It’s one of the biggest mysteries left in medical science.”

“My idea about this condition, and this is shared by others, is that NDPH is not a diagnosis that describes a cohesive group of patients but rather a group of people who share certain features,” Morris Levin, MD, director of the Headache Center at the University of California, San Francisco, said in an interview. “And they would be better served if this diagnosis was split into different categories.”

While praising Dr. Evans and Dr. Turner for their categorization and classification work, Dr. Levin asked, “Let’s say you diagnose someone with NDPH; does that in any way help you with management of this person? The answer is no. Some might say, ‘If you put the patients in the migraine phenotype group, then you can use migraine treatments.’ My point would be: then call it migraine.

“I believe another way to approach NDPH might be to create subcategories of migraine and tension-type headaches,” he added. “A migraine that is either intermittent or nonexistent suddenly becomes daily. That could be a subcategory; rather than being called NDPH, call it ‘new persistent chronic migraine.’ Or ‘new persistent chronic tension-type headache.’ Perhaps that would serve us better in terms of grasping the underlying mechanisms and the best treatment for these patients.”

Along the same lines, Dr. Markley echoed Dr. Evans’ call for more prospective studies and more research on possible medication, hoping to fuel further understanding of this debilitating disorder.

“I think this will be a landmark study for people to look back on,” he said, “especially for anyone going into the headache specialty who has never heard of this type of headache and keeps wondering why they can’t help certain patients, no matter how many medications they try.”

The authors acknowledged their study’s limitations, including its single-center nature and the data abstraction process being performed by just one person. They added, however, that Dr. Evans is a “very experienced researcher with more than 30 years of experience in headache medicine who was abstracting his own patients, data that were very familiar to him.”

Dr. Evans and Dr. Turner declared no potential conflicts of interest.

Collaboration between specialized centers and local oncologists could improve equitable access to cellular therapies for patients with diffuse, large B-cell lymphoma (DLBCL), but other “multifaceted and personalized” strategies are also needed, a new study shows.

Fox Chase Cancer Center, Philadelphia

The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
 

Treatment decision factors

They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.

When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.

Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.

However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).

Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.

“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.

Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
 

Why the findings matter

“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.

“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.

“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”

Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.

He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.

These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.

“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
 

Personalized treatment strategies

The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.

The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.

For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.

Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.

“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”

Next steps

Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.

“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.

Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.

[email protected]

Collaboration between specialized centers and local oncologists could improve equitable access to cellular therapies for patients with diffuse, large B-cell lymphoma (DLBCL), but other “multifaceted and personalized” strategies are also needed, a new study shows.

Fox Chase Cancer Center, Philadelphia

The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
 

Treatment decision factors

They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.

When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.

Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.

However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).

Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.

“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.

Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
 

Why the findings matter

“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.

“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.

“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”

Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.

He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.

These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.

“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
 

Personalized treatment strategies

The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.

The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.

For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.

Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.

“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”

Next steps

Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.

“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.

Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.

[email protected]

Collaboration between specialized centers and local oncologists could improve equitable access to cellular therapies for patients with diffuse, large B-cell lymphoma (DLBCL), but other “multifaceted and personalized” strategies are also needed, a new study shows.

Fox Chase Cancer Center, Philadelphia

The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
 

Treatment decision factors

They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.

When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.

Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.

However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).

Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.

“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.

Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
 

Why the findings matter

“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.

“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.

“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”

Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.

He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.

These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.

“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
 

Personalized treatment strategies

The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.

The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.

For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.

Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.

“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”

Next steps

Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.

“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.

Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.

[email protected]

For over a decade, the influential National Comprehensive Cancer Network (NCCN) has been recommending that men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option.

But the NCCN has now reversed this long-standing recommendation in the latest revision of its prostate cancer guideline.

The organization now recommends that low-risk disease be managed with either active surveillance or radiation therapy or surgery, with equal weight given to all three of these initial options.

The change is seen by some as a retreat to the past and was harshly criticized by many experts on Twitter. The complaints were voiced in unusually blunt and strong language for physicians.

“This is a terrible step back that impacts every urologist,” commented John Griffith, MD, of Hartford Healthcare, who practices in New Britain, Conn.

Dr. Griffith explained that he prints out the NCCN guidance with “every patient newly diagnosed” and that the preferred designation is a “huge help” in reassuring them about not treating low-risk disease initially.

In a Twitter thread, Benjamin Davies, MD, of the University of Pittsburgh, facetiously wondered if a time warp was at play: “To suggest for a millisecond that active surveillance isn’t the preferred method for low-risk men is bizarre thinking ... Is this 1980?”

“I’m baffled,” said Brian Chapin, MD, of MD Anderson Cancer Center, Houston, in another Twitter thread.

“This is ludicrous,” said Andrew Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City in a tweet.

Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia, commented on Twitter that the change “seems off the rails…a bit stunned by this.”

Matthew Cooperberg, MD, of the University of California San Francisco, and Minhaj Siddiqui, MD, of the University of Maryland in Baltimore both called the move a “step backward.”

Many others also expressed disappointment in the NCCN, whose guidelines are hugely influential because of the role they play clinically as well as with payors and the legal system.

“A huge setback & frankly a disgrace for @NCCN and its processes,” commented Fox Chase’s Dr. Kutikov.

Stacy Loeb, MD, of NYU Langone Health in New York City, suggested the new guidance may stunt use of active surveillance in the United States. She tweeted: “The updated NCCN guideline certainly won’t help the lagging and heterogenous uptake of active surveillance in the U.S. We should be carefully expanding the pool for active surveillance, not narrowing it.”

The purpose of active surveillance is to avoid adverse events from treatment, which can be life-changing as they include incontinence and erectile dysfunction.

The rationale is that many men with low-risk prostate cancer may not need treatment for their disease, as the disease may be slow-growing and may never threaten their life. With active surveillance, men are instead monitored with blood tests, scans, and biopsies to watch for worsening disease, and treated only when there are signs of disease progression.

This active surveillance approach has grown in acceptance among American patients since 2010.

The concern now is that the change in guidance from the NCCN will lead to a reduction in active surveillance, and an increase in initial treatment with surgery and radiotherapy for low-risk disease, which is considered by many to be “overtreatment’ of this disease and may not be medically necessary.  

For example, UCSF’s Dr. Cooperberg said he feared that the changed guidance “will be used by urologists and radiation oncologists to justify overtreatment of low-risk disease.”

Dr. Kutikov agreed but described that possibility differently, citing the risk of lawsuits. He observed that without the NCCN’s “medico-legal buffer” of active surveillance as the preferred initial treatment, there are “further incentives” for overtreatment.

The new NCCN guidance also conflicts with the American Urological Association’s guidelines and dissolves what was once a mostly united front from the two major organizations on active surveillance and low-risk disease.

The AUA Guideline reads: “Clinicians should recommend active surveillance as the preferable care option for most low-risk localized prostate cancer patients (Moderate Recommendation; Evidence Level: Grade B)
 

Patients protest change in wording

Not surprisingly, the revised NCCN guidance was criticized by multiple patient advocacy groups, including Active Surveillance Patients International (ASPI), which wrote a letter to the NCCN protesting the change.

In that letter, the ASPI writes that active surveillance is now chosen as the initial approach for low-risk prostate cancer in about 90% of cases in some European nations, and in about 50% of cases in the United States. It also warns that eliminating the word “preferred” from the NCCN guidelines represents a retreat, and “will have repercussions far beyond what we may first conceive.” 

“Active surveillance should be the preferred choice to preserve quality of life for men with low-risk cancer,” the advocacy group states. “The PIVOT trials indicate for low-risk disease there is basically no advantage to intervention. Why would one risk the side effects if they knew that?”
 

Why now?

The NCCN’s move to alter its low-risk prostate cancer guidance is especially striking because, 11 years ago, the NCCN broke new ground in recommending active surveillance as the sole initial treatment option for low-risk men. (It was also the first guidelines group to recommend the same for very low-risk men.)

So why the change now? This news organization requested, but did not receive,  comment from the NCCN and its chair of the prostate cancer panel, Edward Schaeffer, MD, of Northwestern University in Chicago.  

However, on Twitter, Dr. Schaeffer hinted at what had turned the tables for the NCCN panel – the risk that, over time, some men with low-risk disease who are on active surveillance are reclassified on biopsy as having a higher risk.

He highlighted a 2020 study on that very subject from the University of California, San Francisco, published in the Journal of Urology. Those authors concluded that: “Given the heterogeneity of the disease, some tumors characterized as low risk may merit early treatment while others may be followed much less intensely over some time interval.”

Dr. Schaeffer tweeted: “I think this nicely sums up the low-risk space ...”

Experts reacting to Dr. Schaeffer’s tweet were not swayed.

Looking at additional measures such as genomic scores and PSA density, as advocated by Dr. Schaeffer via the posted 2020 study, is good for assessing individual risk, “but still, active surveillance is the preferred option for low risk,” said MD Anderson’s Dr. Chapin.

UCSF’s Dr. Cooperberg, who was a co-author on that 2020 Journal of Urology paper,  commented that the university’s urology department had “spent the past quarter century arguing active surveillance is ‘preferred’ for almost all low risk [disease]!”

“Many on active surveillance need treatment someday, but that does not justify immediate overtreatment,” he concluded.

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

For over a decade, the influential National Comprehensive Cancer Network (NCCN) has been recommending that men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option.

But the NCCN has now reversed this long-standing recommendation in the latest revision of its prostate cancer guideline.

The organization now recommends that low-risk disease be managed with either active surveillance or radiation therapy or surgery, with equal weight given to all three of these initial options.

The change is seen by some as a retreat to the past and was harshly criticized by many experts on Twitter. The complaints were voiced in unusually blunt and strong language for physicians.

“This is a terrible step back that impacts every urologist,” commented John Griffith, MD, of Hartford Healthcare, who practices in New Britain, Conn.

Dr. Griffith explained that he prints out the NCCN guidance with “every patient newly diagnosed” and that the preferred designation is a “huge help” in reassuring them about not treating low-risk disease initially.

In a Twitter thread, Benjamin Davies, MD, of the University of Pittsburgh, facetiously wondered if a time warp was at play: “To suggest for a millisecond that active surveillance isn’t the preferred method for low-risk men is bizarre thinking ... Is this 1980?”

“I’m baffled,” said Brian Chapin, MD, of MD Anderson Cancer Center, Houston, in another Twitter thread.

“This is ludicrous,” said Andrew Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City in a tweet.

Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia, commented on Twitter that the change “seems off the rails…a bit stunned by this.”

Matthew Cooperberg, MD, of the University of California San Francisco, and Minhaj Siddiqui, MD, of the University of Maryland in Baltimore both called the move a “step backward.”

Many others also expressed disappointment in the NCCN, whose guidelines are hugely influential because of the role they play clinically as well as with payors and the legal system.

“A huge setback & frankly a disgrace for @NCCN and its processes,” commented Fox Chase’s Dr. Kutikov.

Stacy Loeb, MD, of NYU Langone Health in New York City, suggested the new guidance may stunt use of active surveillance in the United States. She tweeted: “The updated NCCN guideline certainly won’t help the lagging and heterogenous uptake of active surveillance in the U.S. We should be carefully expanding the pool for active surveillance, not narrowing it.”

The purpose of active surveillance is to avoid adverse events from treatment, which can be life-changing as they include incontinence and erectile dysfunction.

The rationale is that many men with low-risk prostate cancer may not need treatment for their disease, as the disease may be slow-growing and may never threaten their life. With active surveillance, men are instead monitored with blood tests, scans, and biopsies to watch for worsening disease, and treated only when there are signs of disease progression.

This active surveillance approach has grown in acceptance among American patients since 2010.

The concern now is that the change in guidance from the NCCN will lead to a reduction in active surveillance, and an increase in initial treatment with surgery and radiotherapy for low-risk disease, which is considered by many to be “overtreatment’ of this disease and may not be medically necessary.  

For example, UCSF’s Dr. Cooperberg said he feared that the changed guidance “will be used by urologists and radiation oncologists to justify overtreatment of low-risk disease.”

Dr. Kutikov agreed but described that possibility differently, citing the risk of lawsuits. He observed that without the NCCN’s “medico-legal buffer” of active surveillance as the preferred initial treatment, there are “further incentives” for overtreatment.

The new NCCN guidance also conflicts with the American Urological Association’s guidelines and dissolves what was once a mostly united front from the two major organizations on active surveillance and low-risk disease.

The AUA Guideline reads: “Clinicians should recommend active surveillance as the preferable care option for most low-risk localized prostate cancer patients (Moderate Recommendation; Evidence Level: Grade B)
 

Patients protest change in wording

Not surprisingly, the revised NCCN guidance was criticized by multiple patient advocacy groups, including Active Surveillance Patients International (ASPI), which wrote a letter to the NCCN protesting the change.

In that letter, the ASPI writes that active surveillance is now chosen as the initial approach for low-risk prostate cancer in about 90% of cases in some European nations, and in about 50% of cases in the United States. It also warns that eliminating the word “preferred” from the NCCN guidelines represents a retreat, and “will have repercussions far beyond what we may first conceive.” 

“Active surveillance should be the preferred choice to preserve quality of life for men with low-risk cancer,” the advocacy group states. “The PIVOT trials indicate for low-risk disease there is basically no advantage to intervention. Why would one risk the side effects if they knew that?”
 

Why now?

The NCCN’s move to alter its low-risk prostate cancer guidance is especially striking because, 11 years ago, the NCCN broke new ground in recommending active surveillance as the sole initial treatment option for low-risk men. (It was also the first guidelines group to recommend the same for very low-risk men.)

So why the change now? This news organization requested, but did not receive,  comment from the NCCN and its chair of the prostate cancer panel, Edward Schaeffer, MD, of Northwestern University in Chicago.  

However, on Twitter, Dr. Schaeffer hinted at what had turned the tables for the NCCN panel – the risk that, over time, some men with low-risk disease who are on active surveillance are reclassified on biopsy as having a higher risk.

He highlighted a 2020 study on that very subject from the University of California, San Francisco, published in the Journal of Urology. Those authors concluded that: “Given the heterogeneity of the disease, some tumors characterized as low risk may merit early treatment while others may be followed much less intensely over some time interval.”

Dr. Schaeffer tweeted: “I think this nicely sums up the low-risk space ...”

Experts reacting to Dr. Schaeffer’s tweet were not swayed.

Looking at additional measures such as genomic scores and PSA density, as advocated by Dr. Schaeffer via the posted 2020 study, is good for assessing individual risk, “but still, active surveillance is the preferred option for low risk,” said MD Anderson’s Dr. Chapin.

UCSF’s Dr. Cooperberg, who was a co-author on that 2020 Journal of Urology paper,  commented that the university’s urology department had “spent the past quarter century arguing active surveillance is ‘preferred’ for almost all low risk [disease]!”

“Many on active surveillance need treatment someday, but that does not justify immediate overtreatment,” he concluded.

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

For over a decade, the influential National Comprehensive Cancer Network (NCCN) has been recommending that men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option.

But the NCCN has now reversed this long-standing recommendation in the latest revision of its prostate cancer guideline.

The organization now recommends that low-risk disease be managed with either active surveillance or radiation therapy or surgery, with equal weight given to all three of these initial options.

The change is seen by some as a retreat to the past and was harshly criticized by many experts on Twitter. The complaints were voiced in unusually blunt and strong language for physicians.

“This is a terrible step back that impacts every urologist,” commented John Griffith, MD, of Hartford Healthcare, who practices in New Britain, Conn.

Dr. Griffith explained that he prints out the NCCN guidance with “every patient newly diagnosed” and that the preferred designation is a “huge help” in reassuring them about not treating low-risk disease initially.

In a Twitter thread, Benjamin Davies, MD, of the University of Pittsburgh, facetiously wondered if a time warp was at play: “To suggest for a millisecond that active surveillance isn’t the preferred method for low-risk men is bizarre thinking ... Is this 1980?”

“I’m baffled,” said Brian Chapin, MD, of MD Anderson Cancer Center, Houston, in another Twitter thread.

“This is ludicrous,” said Andrew Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City in a tweet.

Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia, commented on Twitter that the change “seems off the rails…a bit stunned by this.”

Matthew Cooperberg, MD, of the University of California San Francisco, and Minhaj Siddiqui, MD, of the University of Maryland in Baltimore both called the move a “step backward.”

Many others also expressed disappointment in the NCCN, whose guidelines are hugely influential because of the role they play clinically as well as with payors and the legal system.

“A huge setback & frankly a disgrace for @NCCN and its processes,” commented Fox Chase’s Dr. Kutikov.

Stacy Loeb, MD, of NYU Langone Health in New York City, suggested the new guidance may stunt use of active surveillance in the United States. She tweeted: “The updated NCCN guideline certainly won’t help the lagging and heterogenous uptake of active surveillance in the U.S. We should be carefully expanding the pool for active surveillance, not narrowing it.”

The purpose of active surveillance is to avoid adverse events from treatment, which can be life-changing as they include incontinence and erectile dysfunction.

The rationale is that many men with low-risk prostate cancer may not need treatment for their disease, as the disease may be slow-growing and may never threaten their life. With active surveillance, men are instead monitored with blood tests, scans, and biopsies to watch for worsening disease, and treated only when there are signs of disease progression.

This active surveillance approach has grown in acceptance among American patients since 2010.

The concern now is that the change in guidance from the NCCN will lead to a reduction in active surveillance, and an increase in initial treatment with surgery and radiotherapy for low-risk disease, which is considered by many to be “overtreatment’ of this disease and may not be medically necessary.  

For example, UCSF’s Dr. Cooperberg said he feared that the changed guidance “will be used by urologists and radiation oncologists to justify overtreatment of low-risk disease.”

Dr. Kutikov agreed but described that possibility differently, citing the risk of lawsuits. He observed that without the NCCN’s “medico-legal buffer” of active surveillance as the preferred initial treatment, there are “further incentives” for overtreatment.

The new NCCN guidance also conflicts with the American Urological Association’s guidelines and dissolves what was once a mostly united front from the two major organizations on active surveillance and low-risk disease.

The AUA Guideline reads: “Clinicians should recommend active surveillance as the preferable care option for most low-risk localized prostate cancer patients (Moderate Recommendation; Evidence Level: Grade B)
 

Patients protest change in wording

Not surprisingly, the revised NCCN guidance was criticized by multiple patient advocacy groups, including Active Surveillance Patients International (ASPI), which wrote a letter to the NCCN protesting the change.

In that letter, the ASPI writes that active surveillance is now chosen as the initial approach for low-risk prostate cancer in about 90% of cases in some European nations, and in about 50% of cases in the United States. It also warns that eliminating the word “preferred” from the NCCN guidelines represents a retreat, and “will have repercussions far beyond what we may first conceive.” 

“Active surveillance should be the preferred choice to preserve quality of life for men with low-risk cancer,” the advocacy group states. “The PIVOT trials indicate for low-risk disease there is basically no advantage to intervention. Why would one risk the side effects if they knew that?”
 

Why now?

The NCCN’s move to alter its low-risk prostate cancer guidance is especially striking because, 11 years ago, the NCCN broke new ground in recommending active surveillance as the sole initial treatment option for low-risk men. (It was also the first guidelines group to recommend the same for very low-risk men.)

So why the change now? This news organization requested, but did not receive,  comment from the NCCN and its chair of the prostate cancer panel, Edward Schaeffer, MD, of Northwestern University in Chicago.  

However, on Twitter, Dr. Schaeffer hinted at what had turned the tables for the NCCN panel – the risk that, over time, some men with low-risk disease who are on active surveillance are reclassified on biopsy as having a higher risk.

He highlighted a 2020 study on that very subject from the University of California, San Francisco, published in the Journal of Urology. Those authors concluded that: “Given the heterogeneity of the disease, some tumors characterized as low risk may merit early treatment while others may be followed much less intensely over some time interval.”

Dr. Schaeffer tweeted: “I think this nicely sums up the low-risk space ...”

Experts reacting to Dr. Schaeffer’s tweet were not swayed.

Looking at additional measures such as genomic scores and PSA density, as advocated by Dr. Schaeffer via the posted 2020 study, is good for assessing individual risk, “but still, active surveillance is the preferred option for low risk,” said MD Anderson’s Dr. Chapin.

UCSF’s Dr. Cooperberg, who was a co-author on that 2020 Journal of Urology paper,  commented that the university’s urology department had “spent the past quarter century arguing active surveillance is ‘preferred’ for almost all low risk [disease]!”

“Many on active surveillance need treatment someday, but that does not justify immediate overtreatment,” he concluded.

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

On Nov. 12, president Joe Biden said he will nominate Robert Califf, MD, to be commissioner of the U.S. Food and Drug Administration, the top U.S. regulator of drugs and medical devices.

Dr. Califf, a cardiologist, served as FDA chief in the Obama administration, leading the agency from Feb. 2016 to Jan. 2017.

The coming nomination ends nearly 11 months of speculation over Mr. Biden’s pick to the lead the agency during the ongoing pandemic. Janet Woodcock, MD, an FDA veteran, has been serving as acting commissioner. The White House faced a Tuesday deadline to make a nomination or see Dr. Woodcock’s tenure as acting chief expire under federal law.

The initial reaction to the idea of Dr. Califf’s return to the FDA drew mixed reactions.

The nonprofit watchdog Public Citizen issued a statement about its opposition to the potential nomination of Dr. Califf. Michael Carome, MD, director of Public Citizen’s Health Research Group, said the United States “desperately needs an FDA leader who will reverse the decades-long trend in which the agency’s relationship with the pharmaceutical and medical-device industries has grown dangerously cozier – resulting in regulatory capture of the agency by industry.”

But the idea of Dr. Califf returning to the FDA pleased Harlan Krumholz, MD, a cardiologist who has been a leader in outcomes research.

Dr. Krumholz tweeted that the Biden administration likely was testing the reaction to a possible Dr. Califf nomination before making it official. “I realize that this is being floated and not officially announced ... but the nomination of [Califf] just makes so much sense,” Dr. Krumholz tweeted. Dr. Califf’s “expertise as a researcher, policymaker, clinician are unparalleled. In a time of partisanship, he should be a slam-dunk confirmation.”

Dr. Califf’s 2016 Senate confirmation process was marked by dissent from several Democrats who questioned his ties to industry. But the chamber voted 89-4 to confirm him.

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

On Nov. 12, president Joe Biden said he will nominate Robert Califf, MD, to be commissioner of the U.S. Food and Drug Administration, the top U.S. regulator of drugs and medical devices.

Dr. Califf, a cardiologist, served as FDA chief in the Obama administration, leading the agency from Feb. 2016 to Jan. 2017.

The coming nomination ends nearly 11 months of speculation over Mr. Biden’s pick to the lead the agency during the ongoing pandemic. Janet Woodcock, MD, an FDA veteran, has been serving as acting commissioner. The White House faced a Tuesday deadline to make a nomination or see Dr. Woodcock’s tenure as acting chief expire under federal law.

The initial reaction to the idea of Dr. Califf’s return to the FDA drew mixed reactions.

The nonprofit watchdog Public Citizen issued a statement about its opposition to the potential nomination of Dr. Califf. Michael Carome, MD, director of Public Citizen’s Health Research Group, said the United States “desperately needs an FDA leader who will reverse the decades-long trend in which the agency’s relationship with the pharmaceutical and medical-device industries has grown dangerously cozier – resulting in regulatory capture of the agency by industry.”

But the idea of Dr. Califf returning to the FDA pleased Harlan Krumholz, MD, a cardiologist who has been a leader in outcomes research.

Dr. Krumholz tweeted that the Biden administration likely was testing the reaction to a possible Dr. Califf nomination before making it official. “I realize that this is being floated and not officially announced ... but the nomination of [Califf] just makes so much sense,” Dr. Krumholz tweeted. Dr. Califf’s “expertise as a researcher, policymaker, clinician are unparalleled. In a time of partisanship, he should be a slam-dunk confirmation.”

Dr. Califf’s 2016 Senate confirmation process was marked by dissent from several Democrats who questioned his ties to industry. But the chamber voted 89-4 to confirm him.

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

On Nov. 12, president Joe Biden said he will nominate Robert Califf, MD, to be commissioner of the U.S. Food and Drug Administration, the top U.S. regulator of drugs and medical devices.

Dr. Califf, a cardiologist, served as FDA chief in the Obama administration, leading the agency from Feb. 2016 to Jan. 2017.

The coming nomination ends nearly 11 months of speculation over Mr. Biden’s pick to the lead the agency during the ongoing pandemic. Janet Woodcock, MD, an FDA veteran, has been serving as acting commissioner. The White House faced a Tuesday deadline to make a nomination or see Dr. Woodcock’s tenure as acting chief expire under federal law.

The initial reaction to the idea of Dr. Califf’s return to the FDA drew mixed reactions.

The nonprofit watchdog Public Citizen issued a statement about its opposition to the potential nomination of Dr. Califf. Michael Carome, MD, director of Public Citizen’s Health Research Group, said the United States “desperately needs an FDA leader who will reverse the decades-long trend in which the agency’s relationship with the pharmaceutical and medical-device industries has grown dangerously cozier – resulting in regulatory capture of the agency by industry.”

But the idea of Dr. Califf returning to the FDA pleased Harlan Krumholz, MD, a cardiologist who has been a leader in outcomes research.

Dr. Krumholz tweeted that the Biden administration likely was testing the reaction to a possible Dr. Califf nomination before making it official. “I realize that this is being floated and not officially announced ... but the nomination of [Califf] just makes so much sense,” Dr. Krumholz tweeted. Dr. Califf’s “expertise as a researcher, policymaker, clinician are unparalleled. In a time of partisanship, he should be a slam-dunk confirmation.”

Dr. Califf’s 2016 Senate confirmation process was marked by dissent from several Democrats who questioned his ties to industry. But the chamber voted 89-4 to confirm him.

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

Venetoclax’s regulatory approvals, its success as monotherapy for chronic lymphocytic leukemia (CLL) and other lymphoid neoplasms, and its activity in combination against acute myeloid leukemia (AML) have helped pave the way for BCL2 and MCL1 inhibitors that target prosurvival, antiapoptosis proteins.

A first-in-class specific inhibitor of BCL2, venetoclax has been quickly followed by drugs that target either BCL2 or proteins with similar prosurvival function, especially MCL1. A review by Andrew W. Roberts, MD, of the Walter and Eliza Hall Institute of Medical Research, Melbourne, and associates details their key features, including their activity and tolerability and resistance issues. The review was published in Blood .
 

BH3 mimetics

BH3 mimetics, a new class of small-molecule anticancer drugs, enable specific targeting of BCL2 and MCL1, commonly expressed antiapoptotic proteins in hematologic cancers. The BH3 mimetics inhibit prosurvival BCL2 proteins, enabling activation of the apoptosis effectors BAX and BK that make the outer mitochondrial membranes permeable. This result triggers apoptosis in many cells, while sensitizing others to cell death when the BH3 mimetics are combined with other antineoplastic drugs. The BAX/BAK–driven effect on mitochondrial membranes is to undermine normal energy production, allowing leakage of cell contents, including cytochrome c, a trigger of proteolytic enzymes and cellular demolition.

Navitoclax was the first potent BCL2 inhibitor to enter clinical trials. While it demonstrated moderate single-agent activity in relapsed CLL and indolent B-cell lymphomas, its dose-limiting toxicity of thrombocytopenia precluded further exploration of BCL2 inhibition. Navitoclax is being developed for hematologic disease (for example, myelofibrosis and acute lymphoblastic leukemia). Clinical development of other BH3 mimetics is only in the earliest stages, the authors wrote.

Venetoclax, to avoid this on-target thrombocytopenia, was designed to specifically inhibit BCL2 with great selectivity, a feature not found in naturally occurring BH3-only proteins. The fact that it could inhibit a single prosurvival protein and have important clinical activity proved enormously stimulating to development of this drug class. Potent BH3 mimetics now can also selectively target MCL1, which plays a central role in plasma cells (mature B lymphocytes are highly reliant on BCL2).

In CLL, dependence on BCL2 is high. Venetoclax, since it was first approved by the Food and Drug Administration in April 2016 as monotherapy for relapsed/refractory del(17p) CLL, has been approved widely in combination with rituximab in relapsed/refractory CLL and for unfit patients with newly diagnosed CLL in combination with obinutuzumab. With venetoclax monotherapy, quickly achieved high objective response rates (79%) and complete remissions (20%) revealed the drug’s dose-limiting toxicity of tumor lysis syndrome (TLS). This necessitated gradual ramp-up dosing in those with high disease burden or reduced renal function. Also, despite the adoption of a venetoclax/rituximab combination as standard for relapsed/refractory CLL, the authors underscored that evidence for an additive rituximab benefit is modest and limited.
 

Resistance

While resistance to venetoclax leading to treatment failure is uncommon in the first year, secondary resistance occurs through several independently occurring mechanisms, including mutations in BCL2 (for example, Gly101Val), overexpression of MCL1, and overexpression of BCLxL. Usual venetoclax therapy is now time limited. Early data on re-exposure shows high rates (about 70%) of secondary responses.

AML

In AML, a more heterogeneous disease than CLL, BCL2 expression varies widely and can be heterogeneous even within a single patient’s leukemic cell population. While responses to venetoclax monotherapy were not durable, combination therapy with azacitidine has revealed enhanced activity. The venetoclax/azacitidine combination has been widely adopted as first-line therapy for older and unfit AML patients. Myelosuppression is the major toxicity.

“As venetoclax is the first in a new class of anticancer drug,” Andrew W. Roberts, MD, said in an interview, “we are still in the process of working out how it can be best utilized. Regimens free of DNA-damaging chemotherapy using this BCL2 inhibitor in combination with obinutuzumab or rituximab in CLL are established. Across B-cell neoplasia (e.g. CLL, mantle cell lymphoma, follicular lymphoma), the challenge is to work out whether venetoclax can enhance other ‘chemotherapy-free’ regimens.” He continued: “In contrast, for AML, learning how venetoclax can be safely combined with intensive chemotherapy is a priority, as we seek to improve outcomes for patients with poor prognosis disease. For MCL1 inhibitors, there is excitement about their potential, but their clinical development remains in its infancy.”

The authors reported multiple financial disclosures.

Venetoclax’s regulatory approvals, its success as monotherapy for chronic lymphocytic leukemia (CLL) and other lymphoid neoplasms, and its activity in combination against acute myeloid leukemia (AML) have helped pave the way for BCL2 and MCL1 inhibitors that target prosurvival, antiapoptosis proteins.

A first-in-class specific inhibitor of BCL2, venetoclax has been quickly followed by drugs that target either BCL2 or proteins with similar prosurvival function, especially MCL1. A review by Andrew W. Roberts, MD, of the Walter and Eliza Hall Institute of Medical Research, Melbourne, and associates details their key features, including their activity and tolerability and resistance issues. The review was published in Blood .
 

BH3 mimetics

BH3 mimetics, a new class of small-molecule anticancer drugs, enable specific targeting of BCL2 and MCL1, commonly expressed antiapoptotic proteins in hematologic cancers. The BH3 mimetics inhibit prosurvival BCL2 proteins, enabling activation of the apoptosis effectors BAX and BK that make the outer mitochondrial membranes permeable. This result triggers apoptosis in many cells, while sensitizing others to cell death when the BH3 mimetics are combined with other antineoplastic drugs. The BAX/BAK–driven effect on mitochondrial membranes is to undermine normal energy production, allowing leakage of cell contents, including cytochrome c, a trigger of proteolytic enzymes and cellular demolition.

Navitoclax was the first potent BCL2 inhibitor to enter clinical trials. While it demonstrated moderate single-agent activity in relapsed CLL and indolent B-cell lymphomas, its dose-limiting toxicity of thrombocytopenia precluded further exploration of BCL2 inhibition. Navitoclax is being developed for hematologic disease (for example, myelofibrosis and acute lymphoblastic leukemia). Clinical development of other BH3 mimetics is only in the earliest stages, the authors wrote.

Venetoclax, to avoid this on-target thrombocytopenia, was designed to specifically inhibit BCL2 with great selectivity, a feature not found in naturally occurring BH3-only proteins. The fact that it could inhibit a single prosurvival protein and have important clinical activity proved enormously stimulating to development of this drug class. Potent BH3 mimetics now can also selectively target MCL1, which plays a central role in plasma cells (mature B lymphocytes are highly reliant on BCL2).

In CLL, dependence on BCL2 is high. Venetoclax, since it was first approved by the Food and Drug Administration in April 2016 as monotherapy for relapsed/refractory del(17p) CLL, has been approved widely in combination with rituximab in relapsed/refractory CLL and for unfit patients with newly diagnosed CLL in combination with obinutuzumab. With venetoclax monotherapy, quickly achieved high objective response rates (79%) and complete remissions (20%) revealed the drug’s dose-limiting toxicity of tumor lysis syndrome (TLS). This necessitated gradual ramp-up dosing in those with high disease burden or reduced renal function. Also, despite the adoption of a venetoclax/rituximab combination as standard for relapsed/refractory CLL, the authors underscored that evidence for an additive rituximab benefit is modest and limited.
 

Resistance

While resistance to venetoclax leading to treatment failure is uncommon in the first year, secondary resistance occurs through several independently occurring mechanisms, including mutations in BCL2 (for example, Gly101Val), overexpression of MCL1, and overexpression of BCLxL. Usual venetoclax therapy is now time limited. Early data on re-exposure shows high rates (about 70%) of secondary responses.

AML

In AML, a more heterogeneous disease than CLL, BCL2 expression varies widely and can be heterogeneous even within a single patient’s leukemic cell population. While responses to venetoclax monotherapy were not durable, combination therapy with azacitidine has revealed enhanced activity. The venetoclax/azacitidine combination has been widely adopted as first-line therapy for older and unfit AML patients. Myelosuppression is the major toxicity.

“As venetoclax is the first in a new class of anticancer drug,” Andrew W. Roberts, MD, said in an interview, “we are still in the process of working out how it can be best utilized. Regimens free of DNA-damaging chemotherapy using this BCL2 inhibitor in combination with obinutuzumab or rituximab in CLL are established. Across B-cell neoplasia (e.g. CLL, mantle cell lymphoma, follicular lymphoma), the challenge is to work out whether venetoclax can enhance other ‘chemotherapy-free’ regimens.” He continued: “In contrast, for AML, learning how venetoclax can be safely combined with intensive chemotherapy is a priority, as we seek to improve outcomes for patients with poor prognosis disease. For MCL1 inhibitors, there is excitement about their potential, but their clinical development remains in its infancy.”

The authors reported multiple financial disclosures.

Venetoclax’s regulatory approvals, its success as monotherapy for chronic lymphocytic leukemia (CLL) and other lymphoid neoplasms, and its activity in combination against acute myeloid leukemia (AML) have helped pave the way for BCL2 and MCL1 inhibitors that target prosurvival, antiapoptosis proteins.

A first-in-class specific inhibitor of BCL2, venetoclax has been quickly followed by drugs that target either BCL2 or proteins with similar prosurvival function, especially MCL1. A review by Andrew W. Roberts, MD, of the Walter and Eliza Hall Institute of Medical Research, Melbourne, and associates details their key features, including their activity and tolerability and resistance issues. The review was published in Blood .
 

BH3 mimetics

BH3 mimetics, a new class of small-molecule anticancer drugs, enable specific targeting of BCL2 and MCL1, commonly expressed antiapoptotic proteins in hematologic cancers. The BH3 mimetics inhibit prosurvival BCL2 proteins, enabling activation of the apoptosis effectors BAX and BK that make the outer mitochondrial membranes permeable. This result triggers apoptosis in many cells, while sensitizing others to cell death when the BH3 mimetics are combined with other antineoplastic drugs. The BAX/BAK–driven effect on mitochondrial membranes is to undermine normal energy production, allowing leakage of cell contents, including cytochrome c, a trigger of proteolytic enzymes and cellular demolition.

Navitoclax was the first potent BCL2 inhibitor to enter clinical trials. While it demonstrated moderate single-agent activity in relapsed CLL and indolent B-cell lymphomas, its dose-limiting toxicity of thrombocytopenia precluded further exploration of BCL2 inhibition. Navitoclax is being developed for hematologic disease (for example, myelofibrosis and acute lymphoblastic leukemia). Clinical development of other BH3 mimetics is only in the earliest stages, the authors wrote.

Venetoclax, to avoid this on-target thrombocytopenia, was designed to specifically inhibit BCL2 with great selectivity, a feature not found in naturally occurring BH3-only proteins. The fact that it could inhibit a single prosurvival protein and have important clinical activity proved enormously stimulating to development of this drug class. Potent BH3 mimetics now can also selectively target MCL1, which plays a central role in plasma cells (mature B lymphocytes are highly reliant on BCL2).

In CLL, dependence on BCL2 is high. Venetoclax, since it was first approved by the Food and Drug Administration in April 2016 as monotherapy for relapsed/refractory del(17p) CLL, has been approved widely in combination with rituximab in relapsed/refractory CLL and for unfit patients with newly diagnosed CLL in combination with obinutuzumab. With venetoclax monotherapy, quickly achieved high objective response rates (79%) and complete remissions (20%) revealed the drug’s dose-limiting toxicity of tumor lysis syndrome (TLS). This necessitated gradual ramp-up dosing in those with high disease burden or reduced renal function. Also, despite the adoption of a venetoclax/rituximab combination as standard for relapsed/refractory CLL, the authors underscored that evidence for an additive rituximab benefit is modest and limited.
 

Resistance

While resistance to venetoclax leading to treatment failure is uncommon in the first year, secondary resistance occurs through several independently occurring mechanisms, including mutations in BCL2 (for example, Gly101Val), overexpression of MCL1, and overexpression of BCLxL. Usual venetoclax therapy is now time limited. Early data on re-exposure shows high rates (about 70%) of secondary responses.

AML

In AML, a more heterogeneous disease than CLL, BCL2 expression varies widely and can be heterogeneous even within a single patient’s leukemic cell population. While responses to venetoclax monotherapy were not durable, combination therapy with azacitidine has revealed enhanced activity. The venetoclax/azacitidine combination has been widely adopted as first-line therapy for older and unfit AML patients. Myelosuppression is the major toxicity.

“As venetoclax is the first in a new class of anticancer drug,” Andrew W. Roberts, MD, said in an interview, “we are still in the process of working out how it can be best utilized. Regimens free of DNA-damaging chemotherapy using this BCL2 inhibitor in combination with obinutuzumab or rituximab in CLL are established. Across B-cell neoplasia (e.g. CLL, mantle cell lymphoma, follicular lymphoma), the challenge is to work out whether venetoclax can enhance other ‘chemotherapy-free’ regimens.” He continued: “In contrast, for AML, learning how venetoclax can be safely combined with intensive chemotherapy is a priority, as we seek to improve outcomes for patients with poor prognosis disease. For MCL1 inhibitors, there is excitement about their potential, but their clinical development remains in its infancy.”

The authors reported multiple financial disclosures.

COVID-19 has been difficult for parents trying to balance careers, home life, and keeping their loved ones safe. A new study indicates that, not only are physicians not immune to these stressors, but the long-term effects could be devastating for health care overall.

Juanmonino/Getty Images

In a study published Nov. 11, 2021, in JAMA Network Open , researchers found that stresses to work/life balance and family life caused by the pandemic have differed among men and women physicians. Women physicians have borne more of the burden, and the consequences could reach far beyond home.

Physicians and other health care workers have been at the front lines of the COVID-19 pandemic, and their work lives have been the focus of a lot of attention in the media and by researchers. Their family lives, not so much. But physicians have families, and the pandemic has upended almost everything about their lives, particularly where work life and home life intersect. School and day care closures, working from home, working extra hours, or working less – all of these changes have consequences on family life and the mental health of parents who are also physicians.

Findings from a Medscape survey published in early 2021 indicate that more female physicians than male physicians were either “conflicted” or “very conflicted” as parents because of work demands (42% vs. 23%) nearly 6 months into the pandemic.

In the current study, researchers from the University of Michigan, Harvard University, and the Medical University of South Carolina teamed up to investigate gender differences in how work/family factors affected the mental health of early-career physician parents in the United States during the first year of the COVID-19 pandemic. The results suggest that the pandemic has increased gender disparity and added disproportionately to the burden of female physicians.
 

Managing the household falls mostly on moms

Participants were physicians enrolled in the Intern Health Study, a longitudinal study that regularly surveys medical interns in the United States to assess stress and mood. When researchers compared survey results from before the onset of the pandemic (2018) with later results (2020), they found a striking gender difference in how the pandemic has changed family and work duties for physicians.

The authors of the study pointed out that previous research had found that female physicians take on a greater share of household and childcare duties than male physicians. The current study found that their share had increased with the pandemic. Physician moms are now 30 times more likely to be in charge of these tasks than physician dads.

In families in which both parents were physicians, none of the men said they took the primary role in managing the extra demands caused by the pandemic. In addition, women were twice as likely as men to work primarily from home and to work reduced hours.

The extra stress seems to be taking a toll on women physicians. In the 2020 survey, physician mothers had higher scores for anxiety and depression symptoms, compared with men. Notably, the 2018 survey did not show a significant difference in depression scores between men and women. Nor were there significant differences in depression and anxiety scores between women and men who were not parents or in reports of work/family conflict before and after the pandemic.

In general, the results indicate that the pandemic has only widened the gender gap between women and men physicians when it comes to managing family life and dealing with the stresses of maintaining a suitable work-life balance.
 

‘Long-term repercussions’ for gender equity in medicine

Although these are serious problems for women physicians and their families, the effects go beyond the home and beyond individuals. Even before the pandemic, women in medicine struggled for parity in career advancement and opportunities as well as in pay, and this new setback could make those challenges even greater.

“Even short-term adjustments can have serious long-term repercussions as they may lead to lower earnings and negatively impact opportunities for promotion, further exacerbating gender inequalities in compensation and advancement,” the study’s authors wrote.

The potential damage extends to the entire profession and the health care system itself. The profession is already struggling to retain young female physicians, and this situation is likely to make that problem worse and have long-term consequences. Citing data showing that female physicians spend more time with patients and that their patients may have better outcomes, the authors wrote that the consequences of losing more early-career female physicians “could be devastating to the U.S. health care system, particularly in the context of a global pandemic and an impending physician shortage.”

The sample size was small (276 U.S. physicians), and the study relied on self-reported data. The findings suggest that more research on this topic is needed, especially research that includes other demographic factors, such as sexual orientation and ethnicity. The authors recommend that institutional and public policymakers take into account the effects of the pandemic on physician mothers to ensure that recent gains in gender equity for women physicians do not fall victim to COVID-19.

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

COVID-19 has been difficult for parents trying to balance careers, home life, and keeping their loved ones safe. A new study indicates that, not only are physicians not immune to these stressors, but the long-term effects could be devastating for health care overall.

Juanmonino/Getty Images

In a study published Nov. 11, 2021, in JAMA Network Open , researchers found that stresses to work/life balance and family life caused by the pandemic have differed among men and women physicians. Women physicians have borne more of the burden, and the consequences could reach far beyond home.

Physicians and other health care workers have been at the front lines of the COVID-19 pandemic, and their work lives have been the focus of a lot of attention in the media and by researchers. Their family lives, not so much. But physicians have families, and the pandemic has upended almost everything about their lives, particularly where work life and home life intersect. School and day care closures, working from home, working extra hours, or working less – all of these changes have consequences on family life and the mental health of parents who are also physicians.

Findings from a Medscape survey published in early 2021 indicate that more female physicians than male physicians were either “conflicted” or “very conflicted” as parents because of work demands (42% vs. 23%) nearly 6 months into the pandemic.

In the current study, researchers from the University of Michigan, Harvard University, and the Medical University of South Carolina teamed up to investigate gender differences in how work/family factors affected the mental health of early-career physician parents in the United States during the first year of the COVID-19 pandemic. The results suggest that the pandemic has increased gender disparity and added disproportionately to the burden of female physicians.
 

Managing the household falls mostly on moms

Participants were physicians enrolled in the Intern Health Study, a longitudinal study that regularly surveys medical interns in the United States to assess stress and mood. When researchers compared survey results from before the onset of the pandemic (2018) with later results (2020), they found a striking gender difference in how the pandemic has changed family and work duties for physicians.

The authors of the study pointed out that previous research had found that female physicians take on a greater share of household and childcare duties than male physicians. The current study found that their share had increased with the pandemic. Physician moms are now 30 times more likely to be in charge of these tasks than physician dads.

In families in which both parents were physicians, none of the men said they took the primary role in managing the extra demands caused by the pandemic. In addition, women were twice as likely as men to work primarily from home and to work reduced hours.

The extra stress seems to be taking a toll on women physicians. In the 2020 survey, physician mothers had higher scores for anxiety and depression symptoms, compared with men. Notably, the 2018 survey did not show a significant difference in depression scores between men and women. Nor were there significant differences in depression and anxiety scores between women and men who were not parents or in reports of work/family conflict before and after the pandemic.

In general, the results indicate that the pandemic has only widened the gender gap between women and men physicians when it comes to managing family life and dealing with the stresses of maintaining a suitable work-life balance.
 

‘Long-term repercussions’ for gender equity in medicine

Although these are serious problems for women physicians and their families, the effects go beyond the home and beyond individuals. Even before the pandemic, women in medicine struggled for parity in career advancement and opportunities as well as in pay, and this new setback could make those challenges even greater.

“Even short-term adjustments can have serious long-term repercussions as they may lead to lower earnings and negatively impact opportunities for promotion, further exacerbating gender inequalities in compensation and advancement,” the study’s authors wrote.

The potential damage extends to the entire profession and the health care system itself. The profession is already struggling to retain young female physicians, and this situation is likely to make that problem worse and have long-term consequences. Citing data showing that female physicians spend more time with patients and that their patients may have better outcomes, the authors wrote that the consequences of losing more early-career female physicians “could be devastating to the U.S. health care system, particularly in the context of a global pandemic and an impending physician shortage.”

The sample size was small (276 U.S. physicians), and the study relied on self-reported data. The findings suggest that more research on this topic is needed, especially research that includes other demographic factors, such as sexual orientation and ethnicity. The authors recommend that institutional and public policymakers take into account the effects of the pandemic on physician mothers to ensure that recent gains in gender equity for women physicians do not fall victim to COVID-19.

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

COVID-19 has been difficult for parents trying to balance careers, home life, and keeping their loved ones safe. A new study indicates that, not only are physicians not immune to these stressors, but the long-term effects could be devastating for health care overall.

Juanmonino/Getty Images

In a study published Nov. 11, 2021, in JAMA Network Open , researchers found that stresses to work/life balance and family life caused by the pandemic have differed among men and women physicians. Women physicians have borne more of the burden, and the consequences could reach far beyond home.

Physicians and other health care workers have been at the front lines of the COVID-19 pandemic, and their work lives have been the focus of a lot of attention in the media and by researchers. Their family lives, not so much. But physicians have families, and the pandemic has upended almost everything about their lives, particularly where work life and home life intersect. School and day care closures, working from home, working extra hours, or working less – all of these changes have consequences on family life and the mental health of parents who are also physicians.

Findings from a Medscape survey published in early 2021 indicate that more female physicians than male physicians were either “conflicted” or “very conflicted” as parents because of work demands (42% vs. 23%) nearly 6 months into the pandemic.

In the current study, researchers from the University of Michigan, Harvard University, and the Medical University of South Carolina teamed up to investigate gender differences in how work/family factors affected the mental health of early-career physician parents in the United States during the first year of the COVID-19 pandemic. The results suggest that the pandemic has increased gender disparity and added disproportionately to the burden of female physicians.
 

Managing the household falls mostly on moms

Participants were physicians enrolled in the Intern Health Study, a longitudinal study that regularly surveys medical interns in the United States to assess stress and mood. When researchers compared survey results from before the onset of the pandemic (2018) with later results (2020), they found a striking gender difference in how the pandemic has changed family and work duties for physicians.

The authors of the study pointed out that previous research had found that female physicians take on a greater share of household and childcare duties than male physicians. The current study found that their share had increased with the pandemic. Physician moms are now 30 times more likely to be in charge of these tasks than physician dads.

In families in which both parents were physicians, none of the men said they took the primary role in managing the extra demands caused by the pandemic. In addition, women were twice as likely as men to work primarily from home and to work reduced hours.

The extra stress seems to be taking a toll on women physicians. In the 2020 survey, physician mothers had higher scores for anxiety and depression symptoms, compared with men. Notably, the 2018 survey did not show a significant difference in depression scores between men and women. Nor were there significant differences in depression and anxiety scores between women and men who were not parents or in reports of work/family conflict before and after the pandemic.

In general, the results indicate that the pandemic has only widened the gender gap between women and men physicians when it comes to managing family life and dealing with the stresses of maintaining a suitable work-life balance.
 

‘Long-term repercussions’ for gender equity in medicine

Although these are serious problems for women physicians and their families, the effects go beyond the home and beyond individuals. Even before the pandemic, women in medicine struggled for parity in career advancement and opportunities as well as in pay, and this new setback could make those challenges even greater.

“Even short-term adjustments can have serious long-term repercussions as they may lead to lower earnings and negatively impact opportunities for promotion, further exacerbating gender inequalities in compensation and advancement,” the study’s authors wrote.

The potential damage extends to the entire profession and the health care system itself. The profession is already struggling to retain young female physicians, and this situation is likely to make that problem worse and have long-term consequences. Citing data showing that female physicians spend more time with patients and that their patients may have better outcomes, the authors wrote that the consequences of losing more early-career female physicians “could be devastating to the U.S. health care system, particularly in the context of a global pandemic and an impending physician shortage.”

The sample size was small (276 U.S. physicians), and the study relied on self-reported data. The findings suggest that more research on this topic is needed, especially research that includes other demographic factors, such as sexual orientation and ethnicity. The authors recommend that institutional and public policymakers take into account the effects of the pandemic on physician mothers to ensure that recent gains in gender equity for women physicians do not fall victim to COVID-19.

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