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Is the FDA serotonin syndrome warning unnecessary?
Results from a study that included more than 1,100 patients who were prescribed linezolid, about 20% of whom were also taking antidepressants, showed that serotonin syndrome occurred in fewer than 0.5% of participants – and that the percentage was actually lower among those who took antidepressants, compared with those who did not.
A comparison of participants who took antidepressants to propensity-matched patients who did not take antidepressants showed similar rates of altered mental status, hospitalization, and death between the two groups.
“In this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely [and] concurrent antidepressants did not significantly increase the risk of serotonin syndrome,” Anthony Bai, MD, division of infectious diseases, department of medicine, Queen’s University, Kingston, Ont., and colleagues write.
“These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction,” they warn.
The findings were published online in JAMA Network Open.
Scarce data
Linezolid, a synthetic oxazolidinone antibiotic active against resistant gram-positive bacteria, has bioavailability of 100%, “making it ideal as first-line or step-down oral antibiotic therapy for bacteremia and pneumonia as well as skin and soft tissue infections,” the researchers write.
However, they note its use has been “limited because of concerns of drug interactions,” since it can reversibly inhibit monoamine oxidase (MAO).
Thus, “coadministration with antidepressants, such as nonselective MAO inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and bupropion, may precipitate serotonin syndrome,” they write.
The investigators note that many patients who were taking antidepressants and who also needed linezolid for an infection “could not receive it because of this relative contraindication.” They add that data on the risk of serotonin syndrome associated with linezolid are “scarce” and are based largely on case reports or case series from passive surveillance.
Although a previous review of linezolid trials found “no conclusive evidence” that it increased risk for serotonin syndrome in patients taking serotonergic medication, data on patients outside of trials “are lacking.” In addition, an observational study suggested that an increased risk had a small sample size that “likely led to imprecise estimates with a wide CI and inconclusive results,” the researchers write.
Therefore, they sought to fill the knowledge gap by retrospectively analyzing data drawn from the ICES database, an independent nonprofit research institute funded by the Ontario Ministry of Health. This was done in order to “estimate the incidence of serotonin syndrome and how this risk changes because of concomitant antidepressant use in patients receiving linezolid treatment,” they write.
The study included a convenience sample of Ontario-based adults (n = 1,134, 52.5% men) who were dispensed oral linezolid 600 mg twice daily between Oct. 1, 2014, and Jan. 1, 2021. All patients were followed for 30 days.
Of these participants, 19% were also taking antidepressants. Close to half (47.9%) were taking an SSRI, 16.7% were taking an SNRI, 7% were taking a tricyclic antidepressant, and 3.3% were taking a norepinephrine and dopamine reuptake inhibitor.
Patients were divided into groups on the basis of age: 66-69 years (19.8%), 70-79 years (41.7%), and 80 years or older (38.4%).
Reassuring findings
Serotonin syndrome occurred in fewer than six patients (< .5%), although the exact numbers were not reported, owing to patient privacy concerns. However, on the basis of fewer than six events, the investigators calculated the risk difference for serotonin syndrome as ranging from −0.5% to 2.3%.
Fewer patients who were taking antidepressants experienced serotonin syndrome, compared with those who were not taking antidepressants.
The investigators estimated a propensity score for antidepressant use that incorporated several patient baseline characteristics, including age, sex, rural home address, Charlson Comorbidity Index, estimated glomerular filtration rate, history of substance use disorder, and days of use of linezolid and other serotonergic medications. They then matched patients who were not taking antidepressants with those who were taking antidepressants (n = 166 each).
The adjusted risk difference for serotonin syndrome was lower in the antidepressant group than in the no-antidepressant group (−1.2%; 95% confidence interval, −2.9% to 0.5%).
“Within this 95% CI, the worst-case scenario would be a 0.5% increase in the risk of serotonin syndrome due to antidepressants, which is equivalent to a number needed to harm of 200,” the researchers write.
For secondary outcomes, they found “similar rates” of altered mental status or confusion, hospitalization, and death within 30 days between the two propensity score–matched groups.
The investigators note that their findings have “limitations, due to the nature of retrospective observational studies.” Moreover, these types of studies are “not efficient because they often focus on a particular adverse event.”
Future research should move beyond observational studies to phase 4 studies, which would “prospectively monitor for all types of adverse events,” they write.
Still, “while waiting for higher-quality evidence, our study adds to the existing evidence for the safety of linezolid even in the context of concomitant antidepressants,” the researchers note.
“Based on the existing evidence, clinicians should be reassured that it appears safe to prescribe oral linezolid to patients taking antidepressants, especially if there are limited antibiotic options or alternative antibiotic options would be inferior,” they add.
‘Consequential relevance’
Commenting on the study, Ipsit Vahia, MD, associate chief of geriatric psychiatry and director of digital psychiatry translation at McLean Hospital, Boston, noted that although studies of drug interactions across age groups “may not accurately reflect the rates of risk for older adults,” the current study focused on linezolid use among older patients.
“One may expect higher rates of serotonin syndrome in older adults, who generally tend to be more sensitive to adverse reactions,” said Dr. Vahia, who is also director of the Technology and Aging Lab at McLean and was not involved with the current research.
“However, the study finds the risk to be low with a number needed to harm of 200,” Dr. Vahia said.
“This retrospective epidemiologic study does not shed light on why this number may be lower than expected, but it has consequential relevance in clinical practice for the management of severe infections among older adults using antidepressants,” he added.
The study was funded by a Queen’s University Research Initiation Grant. Dr. Bai and three of the four other investigators report no relevant financial relationships. Coinvestigator Mark Loeb, MD, reports having received personal fees from the Paladin Labs Advisory Committee, the International Centre for Professional Development in Health and Medicine Advisory Committee, and the Sunovion Advisory Committee outside the submitted work. Dr. Vahia serves as a consultant for Otsuka, has a research collaboration with Emerald Innovations, and receives honorarium as editor for The American Journal of Geriatric Psychiatry.
A version of this article first appeared on Medscape.com.
Results from a study that included more than 1,100 patients who were prescribed linezolid, about 20% of whom were also taking antidepressants, showed that serotonin syndrome occurred in fewer than 0.5% of participants – and that the percentage was actually lower among those who took antidepressants, compared with those who did not.
A comparison of participants who took antidepressants to propensity-matched patients who did not take antidepressants showed similar rates of altered mental status, hospitalization, and death between the two groups.
“In this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely [and] concurrent antidepressants did not significantly increase the risk of serotonin syndrome,” Anthony Bai, MD, division of infectious diseases, department of medicine, Queen’s University, Kingston, Ont., and colleagues write.
“These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction,” they warn.
The findings were published online in JAMA Network Open.
Scarce data
Linezolid, a synthetic oxazolidinone antibiotic active against resistant gram-positive bacteria, has bioavailability of 100%, “making it ideal as first-line or step-down oral antibiotic therapy for bacteremia and pneumonia as well as skin and soft tissue infections,” the researchers write.
However, they note its use has been “limited because of concerns of drug interactions,” since it can reversibly inhibit monoamine oxidase (MAO).
Thus, “coadministration with antidepressants, such as nonselective MAO inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and bupropion, may precipitate serotonin syndrome,” they write.
The investigators note that many patients who were taking antidepressants and who also needed linezolid for an infection “could not receive it because of this relative contraindication.” They add that data on the risk of serotonin syndrome associated with linezolid are “scarce” and are based largely on case reports or case series from passive surveillance.
Although a previous review of linezolid trials found “no conclusive evidence” that it increased risk for serotonin syndrome in patients taking serotonergic medication, data on patients outside of trials “are lacking.” In addition, an observational study suggested that an increased risk had a small sample size that “likely led to imprecise estimates with a wide CI and inconclusive results,” the researchers write.
Therefore, they sought to fill the knowledge gap by retrospectively analyzing data drawn from the ICES database, an independent nonprofit research institute funded by the Ontario Ministry of Health. This was done in order to “estimate the incidence of serotonin syndrome and how this risk changes because of concomitant antidepressant use in patients receiving linezolid treatment,” they write.
The study included a convenience sample of Ontario-based adults (n = 1,134, 52.5% men) who were dispensed oral linezolid 600 mg twice daily between Oct. 1, 2014, and Jan. 1, 2021. All patients were followed for 30 days.
Of these participants, 19% were also taking antidepressants. Close to half (47.9%) were taking an SSRI, 16.7% were taking an SNRI, 7% were taking a tricyclic antidepressant, and 3.3% were taking a norepinephrine and dopamine reuptake inhibitor.
Patients were divided into groups on the basis of age: 66-69 years (19.8%), 70-79 years (41.7%), and 80 years or older (38.4%).
Reassuring findings
Serotonin syndrome occurred in fewer than six patients (< .5%), although the exact numbers were not reported, owing to patient privacy concerns. However, on the basis of fewer than six events, the investigators calculated the risk difference for serotonin syndrome as ranging from −0.5% to 2.3%.
Fewer patients who were taking antidepressants experienced serotonin syndrome, compared with those who were not taking antidepressants.
The investigators estimated a propensity score for antidepressant use that incorporated several patient baseline characteristics, including age, sex, rural home address, Charlson Comorbidity Index, estimated glomerular filtration rate, history of substance use disorder, and days of use of linezolid and other serotonergic medications. They then matched patients who were not taking antidepressants with those who were taking antidepressants (n = 166 each).
The adjusted risk difference for serotonin syndrome was lower in the antidepressant group than in the no-antidepressant group (−1.2%; 95% confidence interval, −2.9% to 0.5%).
“Within this 95% CI, the worst-case scenario would be a 0.5% increase in the risk of serotonin syndrome due to antidepressants, which is equivalent to a number needed to harm of 200,” the researchers write.
For secondary outcomes, they found “similar rates” of altered mental status or confusion, hospitalization, and death within 30 days between the two propensity score–matched groups.
The investigators note that their findings have “limitations, due to the nature of retrospective observational studies.” Moreover, these types of studies are “not efficient because they often focus on a particular adverse event.”
Future research should move beyond observational studies to phase 4 studies, which would “prospectively monitor for all types of adverse events,” they write.
Still, “while waiting for higher-quality evidence, our study adds to the existing evidence for the safety of linezolid even in the context of concomitant antidepressants,” the researchers note.
“Based on the existing evidence, clinicians should be reassured that it appears safe to prescribe oral linezolid to patients taking antidepressants, especially if there are limited antibiotic options or alternative antibiotic options would be inferior,” they add.
‘Consequential relevance’
Commenting on the study, Ipsit Vahia, MD, associate chief of geriatric psychiatry and director of digital psychiatry translation at McLean Hospital, Boston, noted that although studies of drug interactions across age groups “may not accurately reflect the rates of risk for older adults,” the current study focused on linezolid use among older patients.
“One may expect higher rates of serotonin syndrome in older adults, who generally tend to be more sensitive to adverse reactions,” said Dr. Vahia, who is also director of the Technology and Aging Lab at McLean and was not involved with the current research.
“However, the study finds the risk to be low with a number needed to harm of 200,” Dr. Vahia said.
“This retrospective epidemiologic study does not shed light on why this number may be lower than expected, but it has consequential relevance in clinical practice for the management of severe infections among older adults using antidepressants,” he added.
The study was funded by a Queen’s University Research Initiation Grant. Dr. Bai and three of the four other investigators report no relevant financial relationships. Coinvestigator Mark Loeb, MD, reports having received personal fees from the Paladin Labs Advisory Committee, the International Centre for Professional Development in Health and Medicine Advisory Committee, and the Sunovion Advisory Committee outside the submitted work. Dr. Vahia serves as a consultant for Otsuka, has a research collaboration with Emerald Innovations, and receives honorarium as editor for The American Journal of Geriatric Psychiatry.
A version of this article first appeared on Medscape.com.
Results from a study that included more than 1,100 patients who were prescribed linezolid, about 20% of whom were also taking antidepressants, showed that serotonin syndrome occurred in fewer than 0.5% of participants – and that the percentage was actually lower among those who took antidepressants, compared with those who did not.
A comparison of participants who took antidepressants to propensity-matched patients who did not take antidepressants showed similar rates of altered mental status, hospitalization, and death between the two groups.
“In this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely [and] concurrent antidepressants did not significantly increase the risk of serotonin syndrome,” Anthony Bai, MD, division of infectious diseases, department of medicine, Queen’s University, Kingston, Ont., and colleagues write.
“These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction,” they warn.
The findings were published online in JAMA Network Open.
Scarce data
Linezolid, a synthetic oxazolidinone antibiotic active against resistant gram-positive bacteria, has bioavailability of 100%, “making it ideal as first-line or step-down oral antibiotic therapy for bacteremia and pneumonia as well as skin and soft tissue infections,” the researchers write.
However, they note its use has been “limited because of concerns of drug interactions,” since it can reversibly inhibit monoamine oxidase (MAO).
Thus, “coadministration with antidepressants, such as nonselective MAO inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and bupropion, may precipitate serotonin syndrome,” they write.
The investigators note that many patients who were taking antidepressants and who also needed linezolid for an infection “could not receive it because of this relative contraindication.” They add that data on the risk of serotonin syndrome associated with linezolid are “scarce” and are based largely on case reports or case series from passive surveillance.
Although a previous review of linezolid trials found “no conclusive evidence” that it increased risk for serotonin syndrome in patients taking serotonergic medication, data on patients outside of trials “are lacking.” In addition, an observational study suggested that an increased risk had a small sample size that “likely led to imprecise estimates with a wide CI and inconclusive results,” the researchers write.
Therefore, they sought to fill the knowledge gap by retrospectively analyzing data drawn from the ICES database, an independent nonprofit research institute funded by the Ontario Ministry of Health. This was done in order to “estimate the incidence of serotonin syndrome and how this risk changes because of concomitant antidepressant use in patients receiving linezolid treatment,” they write.
The study included a convenience sample of Ontario-based adults (n = 1,134, 52.5% men) who were dispensed oral linezolid 600 mg twice daily between Oct. 1, 2014, and Jan. 1, 2021. All patients were followed for 30 days.
Of these participants, 19% were also taking antidepressants. Close to half (47.9%) were taking an SSRI, 16.7% were taking an SNRI, 7% were taking a tricyclic antidepressant, and 3.3% were taking a norepinephrine and dopamine reuptake inhibitor.
Patients were divided into groups on the basis of age: 66-69 years (19.8%), 70-79 years (41.7%), and 80 years or older (38.4%).
Reassuring findings
Serotonin syndrome occurred in fewer than six patients (< .5%), although the exact numbers were not reported, owing to patient privacy concerns. However, on the basis of fewer than six events, the investigators calculated the risk difference for serotonin syndrome as ranging from −0.5% to 2.3%.
Fewer patients who were taking antidepressants experienced serotonin syndrome, compared with those who were not taking antidepressants.
The investigators estimated a propensity score for antidepressant use that incorporated several patient baseline characteristics, including age, sex, rural home address, Charlson Comorbidity Index, estimated glomerular filtration rate, history of substance use disorder, and days of use of linezolid and other serotonergic medications. They then matched patients who were not taking antidepressants with those who were taking antidepressants (n = 166 each).
The adjusted risk difference for serotonin syndrome was lower in the antidepressant group than in the no-antidepressant group (−1.2%; 95% confidence interval, −2.9% to 0.5%).
“Within this 95% CI, the worst-case scenario would be a 0.5% increase in the risk of serotonin syndrome due to antidepressants, which is equivalent to a number needed to harm of 200,” the researchers write.
For secondary outcomes, they found “similar rates” of altered mental status or confusion, hospitalization, and death within 30 days between the two propensity score–matched groups.
The investigators note that their findings have “limitations, due to the nature of retrospective observational studies.” Moreover, these types of studies are “not efficient because they often focus on a particular adverse event.”
Future research should move beyond observational studies to phase 4 studies, which would “prospectively monitor for all types of adverse events,” they write.
Still, “while waiting for higher-quality evidence, our study adds to the existing evidence for the safety of linezolid even in the context of concomitant antidepressants,” the researchers note.
“Based on the existing evidence, clinicians should be reassured that it appears safe to prescribe oral linezolid to patients taking antidepressants, especially if there are limited antibiotic options or alternative antibiotic options would be inferior,” they add.
‘Consequential relevance’
Commenting on the study, Ipsit Vahia, MD, associate chief of geriatric psychiatry and director of digital psychiatry translation at McLean Hospital, Boston, noted that although studies of drug interactions across age groups “may not accurately reflect the rates of risk for older adults,” the current study focused on linezolid use among older patients.
“One may expect higher rates of serotonin syndrome in older adults, who generally tend to be more sensitive to adverse reactions,” said Dr. Vahia, who is also director of the Technology and Aging Lab at McLean and was not involved with the current research.
“However, the study finds the risk to be low with a number needed to harm of 200,” Dr. Vahia said.
“This retrospective epidemiologic study does not shed light on why this number may be lower than expected, but it has consequential relevance in clinical practice for the management of severe infections among older adults using antidepressants,” he added.
The study was funded by a Queen’s University Research Initiation Grant. Dr. Bai and three of the four other investigators report no relevant financial relationships. Coinvestigator Mark Loeb, MD, reports having received personal fees from the Paladin Labs Advisory Committee, the International Centre for Professional Development in Health and Medicine Advisory Committee, and the Sunovion Advisory Committee outside the submitted work. Dr. Vahia serves as a consultant for Otsuka, has a research collaboration with Emerald Innovations, and receives honorarium as editor for The American Journal of Geriatric Psychiatry.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Pediatric vaccination rates have failed to recover
I guess we shouldn’t be surprised that vaccination rates in this country fell during the frenzy created by the COVID pandemic. We had a lot on our plates. Schools closed and many of us retreated into what seemed to be the safety of our homes. Parents were reluctant to take their children anywhere, let alone a pediatrician’s office. State health agencies wisely focused on collecting case figures and then shepherding the efforts to immunize against SARS-CoV-2 once vaccines were available. Tracking and promoting the existing children’s vaccinations fell off the priority list, even in places with exemplary vaccination rates.
Whether or not the pandemic is over continues to be a topic for debate, but there is clearly a general shift toward a new normalcy. However, vaccination rates of our children have not rebounded to prepandemic levels. In fact, in some areas they are continuing to fall.
In a recent guest essay in the New York Times, Ezekiel J. Emmanuel, MD, PhD, a physician and professor of medical ethics and health policy at the University of Pennsylvania, and Matthew Guido, his research assistant, explore the reasons for this lack of a significant rebound. The authors cite recent outbreaks of measles in Ohio and polio in New York City as examples of the peril we are facing if we fail to reverse the trend. In some areas measles vaccine rates alarmingly have dipped below the threshold for herd immunity.
While Dr. Emmanuel and Mr. Guido acknowledge that the pandemic was a major driver of the falling vaccination rates they lay blame on the persistent decline on three factors that they view as correctable: nonmedical exemptions, our failure to vigorously enforce existing vaccine requirements, and inadequate public health campaigns.
The authors underestimate the lingering effect of the pandemic on parents’ vaccine hesitancy. As a septuagenarian who often hangs out with other septuagenarians I view the rapid development and effectiveness of the COVID vaccine as astounding and a boost for vaccines in general. However, were I much younger I might treat the vaccine’s success with a shrug. After some initial concern, the younger half of the population didn’t seem to see the illness as much of a threat to themselves or their peers. This attitude was reinforced by the fact that few of their peers, including those who were unvaccinated, were getting seriously ill. Despite all the hype, most parents and their children never ended up getting seriously ill.
You can understand why many parents might be quick to toss what you and I consider a successful COVID vaccine onto what they view as a growing pile of vaccines for diseases that in their experience have never sickened or killed anyone they have known.
Let’s be honest: Over the last half century we have produced several generations of parents who have little knowledge and certainly no personal experience with a childhood disease on the order or magnitude of polio. The vaccines that we have developed during their lifetimes have been targeted at diseases such as haemophilus influenzae meningitis that, while serious and anxiety provoking for pediatricians, occur so sporadically that most parents have no personal experience to motivate them to vaccinate their children.
Dr. Emmanuel and Mr. Guido are correct in advocating for the broader elimination of nonmedical exemptions and urging us to find the political will to vigorously enforce the vaccine requirements we have already enacted. I agree that our promotional campaigns need to be more robust. But, this will be a difficult challenge unless we can impress our audience with our straight talk and honesty. We must acknowledge and then explain why all vaccines are not created equal and that some are of more critical importance than others.
We are slowly learning that education isn’t the cure-all for vaccine hesitancy we once thought it was. And using scare tactics can backfire and create dysfunctional anxiety. We must choosing our words and target audience carefully. And ... having the political will to force parents into doing the right thing will be critical if we wish to restore our vaccination rates.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I guess we shouldn’t be surprised that vaccination rates in this country fell during the frenzy created by the COVID pandemic. We had a lot on our plates. Schools closed and many of us retreated into what seemed to be the safety of our homes. Parents were reluctant to take their children anywhere, let alone a pediatrician’s office. State health agencies wisely focused on collecting case figures and then shepherding the efforts to immunize against SARS-CoV-2 once vaccines were available. Tracking and promoting the existing children’s vaccinations fell off the priority list, even in places with exemplary vaccination rates.
Whether or not the pandemic is over continues to be a topic for debate, but there is clearly a general shift toward a new normalcy. However, vaccination rates of our children have not rebounded to prepandemic levels. In fact, in some areas they are continuing to fall.
In a recent guest essay in the New York Times, Ezekiel J. Emmanuel, MD, PhD, a physician and professor of medical ethics and health policy at the University of Pennsylvania, and Matthew Guido, his research assistant, explore the reasons for this lack of a significant rebound. The authors cite recent outbreaks of measles in Ohio and polio in New York City as examples of the peril we are facing if we fail to reverse the trend. In some areas measles vaccine rates alarmingly have dipped below the threshold for herd immunity.
While Dr. Emmanuel and Mr. Guido acknowledge that the pandemic was a major driver of the falling vaccination rates they lay blame on the persistent decline on three factors that they view as correctable: nonmedical exemptions, our failure to vigorously enforce existing vaccine requirements, and inadequate public health campaigns.
The authors underestimate the lingering effect of the pandemic on parents’ vaccine hesitancy. As a septuagenarian who often hangs out with other septuagenarians I view the rapid development and effectiveness of the COVID vaccine as astounding and a boost for vaccines in general. However, were I much younger I might treat the vaccine’s success with a shrug. After some initial concern, the younger half of the population didn’t seem to see the illness as much of a threat to themselves or their peers. This attitude was reinforced by the fact that few of their peers, including those who were unvaccinated, were getting seriously ill. Despite all the hype, most parents and their children never ended up getting seriously ill.
You can understand why many parents might be quick to toss what you and I consider a successful COVID vaccine onto what they view as a growing pile of vaccines for diseases that in their experience have never sickened or killed anyone they have known.
Let’s be honest: Over the last half century we have produced several generations of parents who have little knowledge and certainly no personal experience with a childhood disease on the order or magnitude of polio. The vaccines that we have developed during their lifetimes have been targeted at diseases such as haemophilus influenzae meningitis that, while serious and anxiety provoking for pediatricians, occur so sporadically that most parents have no personal experience to motivate them to vaccinate their children.
Dr. Emmanuel and Mr. Guido are correct in advocating for the broader elimination of nonmedical exemptions and urging us to find the political will to vigorously enforce the vaccine requirements we have already enacted. I agree that our promotional campaigns need to be more robust. But, this will be a difficult challenge unless we can impress our audience with our straight talk and honesty. We must acknowledge and then explain why all vaccines are not created equal and that some are of more critical importance than others.
We are slowly learning that education isn’t the cure-all for vaccine hesitancy we once thought it was. And using scare tactics can backfire and create dysfunctional anxiety. We must choosing our words and target audience carefully. And ... having the political will to force parents into doing the right thing will be critical if we wish to restore our vaccination rates.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I guess we shouldn’t be surprised that vaccination rates in this country fell during the frenzy created by the COVID pandemic. We had a lot on our plates. Schools closed and many of us retreated into what seemed to be the safety of our homes. Parents were reluctant to take their children anywhere, let alone a pediatrician’s office. State health agencies wisely focused on collecting case figures and then shepherding the efforts to immunize against SARS-CoV-2 once vaccines were available. Tracking and promoting the existing children’s vaccinations fell off the priority list, even in places with exemplary vaccination rates.
Whether or not the pandemic is over continues to be a topic for debate, but there is clearly a general shift toward a new normalcy. However, vaccination rates of our children have not rebounded to prepandemic levels. In fact, in some areas they are continuing to fall.
In a recent guest essay in the New York Times, Ezekiel J. Emmanuel, MD, PhD, a physician and professor of medical ethics and health policy at the University of Pennsylvania, and Matthew Guido, his research assistant, explore the reasons for this lack of a significant rebound. The authors cite recent outbreaks of measles in Ohio and polio in New York City as examples of the peril we are facing if we fail to reverse the trend. In some areas measles vaccine rates alarmingly have dipped below the threshold for herd immunity.
While Dr. Emmanuel and Mr. Guido acknowledge that the pandemic was a major driver of the falling vaccination rates they lay blame on the persistent decline on three factors that they view as correctable: nonmedical exemptions, our failure to vigorously enforce existing vaccine requirements, and inadequate public health campaigns.
The authors underestimate the lingering effect of the pandemic on parents’ vaccine hesitancy. As a septuagenarian who often hangs out with other septuagenarians I view the rapid development and effectiveness of the COVID vaccine as astounding and a boost for vaccines in general. However, were I much younger I might treat the vaccine’s success with a shrug. After some initial concern, the younger half of the population didn’t seem to see the illness as much of a threat to themselves or their peers. This attitude was reinforced by the fact that few of their peers, including those who were unvaccinated, were getting seriously ill. Despite all the hype, most parents and their children never ended up getting seriously ill.
You can understand why many parents might be quick to toss what you and I consider a successful COVID vaccine onto what they view as a growing pile of vaccines for diseases that in their experience have never sickened or killed anyone they have known.
Let’s be honest: Over the last half century we have produced several generations of parents who have little knowledge and certainly no personal experience with a childhood disease on the order or magnitude of polio. The vaccines that we have developed during their lifetimes have been targeted at diseases such as haemophilus influenzae meningitis that, while serious and anxiety provoking for pediatricians, occur so sporadically that most parents have no personal experience to motivate them to vaccinate their children.
Dr. Emmanuel and Mr. Guido are correct in advocating for the broader elimination of nonmedical exemptions and urging us to find the political will to vigorously enforce the vaccine requirements we have already enacted. I agree that our promotional campaigns need to be more robust. But, this will be a difficult challenge unless we can impress our audience with our straight talk and honesty. We must acknowledge and then explain why all vaccines are not created equal and that some are of more critical importance than others.
We are slowly learning that education isn’t the cure-all for vaccine hesitancy we once thought it was. And using scare tactics can backfire and create dysfunctional anxiety. We must choosing our words and target audience carefully. And ... having the political will to force parents into doing the right thing will be critical if we wish to restore our vaccination rates.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Do collagen supplements benefit the skin?
SAN DIEGO – When patients ask if collagen supplements can benefit their skin, what should you tell them?
According to Ava Shamban, MD, a dermatologist who practices in Santa Monica, Calif., And in her opinion, more research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation.
“Collagen is the most abundant protein in the skin; it is found only in animal flesh like meat and fish that contain connective tissue,” she said at the annual Masters of Aesthetics Symposium. “We produce less collagen as we age. External factors can slow down our collagen production, including smoking, sun exposure, lack of sleep/exercise, and alcohol consumption.”
Though human studies are lacking, some trials have found that collagen supplements may improve skin hydration and elasticity. “Maybe there’s some benefit, but the digestive process breaks collagen down into amino acids, so I don’t buy it,” she said.
At the meeting, Dr. Shamban discussed other topics related to the effect of supplements and nutrition on the skin:
Can Nutrafol reverse permanent hair loss? “It definitely doesn’t do that,” she said. “Can it help regrow hair? Perhaps.” Nutrafol is an over-the-counter supplement that aims to relieve moderate hair thinning or strengthen hair to prevent breakage, and is physician-formulated with medical-grade ingredients that target root causes of thinning such as stress, lifestyle, hormones, and nutrition.
As for biotin, “we now know that high levels of biotin can actually cause hair loss,” she said. “If you have advanced hair loss, supplements may not work for you. There is no hair regrowth supplement that can bring back a dead hair follicle. Can it help a miniaturized hair follicle? Maybe. Platelet-rich plasma injections have been shown to stimulate hair growth, but only if the follicle is miniaturized, not if it’s totally gone.”
How does the human microbiome affect skin? In a review of sequencing surveys of healthy adults, “the composition of microbial communities was found to be primarily dependent on the physiology of the skin site, with changes in the relative abundance of bacterial taxa associated with moist, dry, and sebaceous environments,” the authors reported . “The microbiome is the genetic material of all the microbes that live inside the body, including bacteria, fungi, protozoa, and viruses,” Dr. Shamban said. “The more diverse the microbiota is, the healthier it’s considered. That diversity is enriched through a diet full of various vegetables and fruits.”
Nearly all adults are colonized with Cutibacterium acnes (formerly Propionibacterium acnes), but only a minority have acne, which highlights the importance of studying diseases in the broader context of host genetics, immune or barrier defects, the microbiome, and the environment, she added. For example, the decreased diversity of the skin microbiome in people with atopic dermatitis has been linked to a reduction in environmental biodiversity in the areas surrounding their homes.
Do adaptogens have a role in skin care? Adaptogens such as ashwagandha, elderberry, ginseng, licorice root, neem, moringa, and reishi mushrooms have been used in Chinese and Ayurvedic medicine for centuries and are purported to promote adaptability, resilience, and survival of living organisms in stress. They appear to affect the neuroendocrine immune system and at low doses may function as mild stress mimetics.
“The idea is that combining adaptogens into skin care can reinforce and support the skin’s resistance against stressors that can accelerate visible signs of aging,” said Dr. Shamban. “They share some similarities with antioxidants in that their main purpose is to protect the body from external stressors such as UV rays, oxidation, and pollution.” More studies should be conducted to verify effectiveness, she said, “but Eastern practices that have incorporated it for centuries shouldn’t be fully dismissed. Most doctors believe adaptogens are safe, but how they interact with the mechanics of the body’s stress response system remains a mystery.”
Embrace the consumption of micronutrients. Inspired by work from dermatologist Zoe Diana Draelos, MD, Dr. Shamban advises patients to eat a “rainbow of different colored foods” every day, especially those rich in vitamins A, C, and E. Green foods are generally rich in vitamin E, brown foods are rich in trace minerals, and blue/purple foods are rich in antioxidants. “It’s always best to get nutrients from a rich, healthy diet, but sometimes our skin requires extra help,” she said.
A randomized, placebo-controlled, double-blind study by French researchers, which showed that skin is prone to seasonal changes during the winter, particularly in exposed areas, also looked at whether a daily micronutrient supplement with ingredients that included green tea extract, blackcurrant seed oil, and magnesium, had an impact on the negative effects of winter weather on the skin. “The data indicate that oral micronutrient supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin,” she said.
Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.
SAN DIEGO – When patients ask if collagen supplements can benefit their skin, what should you tell them?
According to Ava Shamban, MD, a dermatologist who practices in Santa Monica, Calif., And in her opinion, more research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation.
“Collagen is the most abundant protein in the skin; it is found only in animal flesh like meat and fish that contain connective tissue,” she said at the annual Masters of Aesthetics Symposium. “We produce less collagen as we age. External factors can slow down our collagen production, including smoking, sun exposure, lack of sleep/exercise, and alcohol consumption.”
Though human studies are lacking, some trials have found that collagen supplements may improve skin hydration and elasticity. “Maybe there’s some benefit, but the digestive process breaks collagen down into amino acids, so I don’t buy it,” she said.
At the meeting, Dr. Shamban discussed other topics related to the effect of supplements and nutrition on the skin:
Can Nutrafol reverse permanent hair loss? “It definitely doesn’t do that,” she said. “Can it help regrow hair? Perhaps.” Nutrafol is an over-the-counter supplement that aims to relieve moderate hair thinning or strengthen hair to prevent breakage, and is physician-formulated with medical-grade ingredients that target root causes of thinning such as stress, lifestyle, hormones, and nutrition.
As for biotin, “we now know that high levels of biotin can actually cause hair loss,” she said. “If you have advanced hair loss, supplements may not work for you. There is no hair regrowth supplement that can bring back a dead hair follicle. Can it help a miniaturized hair follicle? Maybe. Platelet-rich plasma injections have been shown to stimulate hair growth, but only if the follicle is miniaturized, not if it’s totally gone.”
How does the human microbiome affect skin? In a review of sequencing surveys of healthy adults, “the composition of microbial communities was found to be primarily dependent on the physiology of the skin site, with changes in the relative abundance of bacterial taxa associated with moist, dry, and sebaceous environments,” the authors reported . “The microbiome is the genetic material of all the microbes that live inside the body, including bacteria, fungi, protozoa, and viruses,” Dr. Shamban said. “The more diverse the microbiota is, the healthier it’s considered. That diversity is enriched through a diet full of various vegetables and fruits.”
Nearly all adults are colonized with Cutibacterium acnes (formerly Propionibacterium acnes), but only a minority have acne, which highlights the importance of studying diseases in the broader context of host genetics, immune or barrier defects, the microbiome, and the environment, she added. For example, the decreased diversity of the skin microbiome in people with atopic dermatitis has been linked to a reduction in environmental biodiversity in the areas surrounding their homes.
Do adaptogens have a role in skin care? Adaptogens such as ashwagandha, elderberry, ginseng, licorice root, neem, moringa, and reishi mushrooms have been used in Chinese and Ayurvedic medicine for centuries and are purported to promote adaptability, resilience, and survival of living organisms in stress. They appear to affect the neuroendocrine immune system and at low doses may function as mild stress mimetics.
“The idea is that combining adaptogens into skin care can reinforce and support the skin’s resistance against stressors that can accelerate visible signs of aging,” said Dr. Shamban. “They share some similarities with antioxidants in that their main purpose is to protect the body from external stressors such as UV rays, oxidation, and pollution.” More studies should be conducted to verify effectiveness, she said, “but Eastern practices that have incorporated it for centuries shouldn’t be fully dismissed. Most doctors believe adaptogens are safe, but how they interact with the mechanics of the body’s stress response system remains a mystery.”
Embrace the consumption of micronutrients. Inspired by work from dermatologist Zoe Diana Draelos, MD, Dr. Shamban advises patients to eat a “rainbow of different colored foods” every day, especially those rich in vitamins A, C, and E. Green foods are generally rich in vitamin E, brown foods are rich in trace minerals, and blue/purple foods are rich in antioxidants. “It’s always best to get nutrients from a rich, healthy diet, but sometimes our skin requires extra help,” she said.
A randomized, placebo-controlled, double-blind study by French researchers, which showed that skin is prone to seasonal changes during the winter, particularly in exposed areas, also looked at whether a daily micronutrient supplement with ingredients that included green tea extract, blackcurrant seed oil, and magnesium, had an impact on the negative effects of winter weather on the skin. “The data indicate that oral micronutrient supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin,” she said.
Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.
SAN DIEGO – When patients ask if collagen supplements can benefit their skin, what should you tell them?
According to Ava Shamban, MD, a dermatologist who practices in Santa Monica, Calif., And in her opinion, more research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation.
“Collagen is the most abundant protein in the skin; it is found only in animal flesh like meat and fish that contain connective tissue,” she said at the annual Masters of Aesthetics Symposium. “We produce less collagen as we age. External factors can slow down our collagen production, including smoking, sun exposure, lack of sleep/exercise, and alcohol consumption.”
Though human studies are lacking, some trials have found that collagen supplements may improve skin hydration and elasticity. “Maybe there’s some benefit, but the digestive process breaks collagen down into amino acids, so I don’t buy it,” she said.
At the meeting, Dr. Shamban discussed other topics related to the effect of supplements and nutrition on the skin:
Can Nutrafol reverse permanent hair loss? “It definitely doesn’t do that,” she said. “Can it help regrow hair? Perhaps.” Nutrafol is an over-the-counter supplement that aims to relieve moderate hair thinning or strengthen hair to prevent breakage, and is physician-formulated with medical-grade ingredients that target root causes of thinning such as stress, lifestyle, hormones, and nutrition.
As for biotin, “we now know that high levels of biotin can actually cause hair loss,” she said. “If you have advanced hair loss, supplements may not work for you. There is no hair regrowth supplement that can bring back a dead hair follicle. Can it help a miniaturized hair follicle? Maybe. Platelet-rich plasma injections have been shown to stimulate hair growth, but only if the follicle is miniaturized, not if it’s totally gone.”
How does the human microbiome affect skin? In a review of sequencing surveys of healthy adults, “the composition of microbial communities was found to be primarily dependent on the physiology of the skin site, with changes in the relative abundance of bacterial taxa associated with moist, dry, and sebaceous environments,” the authors reported . “The microbiome is the genetic material of all the microbes that live inside the body, including bacteria, fungi, protozoa, and viruses,” Dr. Shamban said. “The more diverse the microbiota is, the healthier it’s considered. That diversity is enriched through a diet full of various vegetables and fruits.”
Nearly all adults are colonized with Cutibacterium acnes (formerly Propionibacterium acnes), but only a minority have acne, which highlights the importance of studying diseases in the broader context of host genetics, immune or barrier defects, the microbiome, and the environment, she added. For example, the decreased diversity of the skin microbiome in people with atopic dermatitis has been linked to a reduction in environmental biodiversity in the areas surrounding their homes.
Do adaptogens have a role in skin care? Adaptogens such as ashwagandha, elderberry, ginseng, licorice root, neem, moringa, and reishi mushrooms have been used in Chinese and Ayurvedic medicine for centuries and are purported to promote adaptability, resilience, and survival of living organisms in stress. They appear to affect the neuroendocrine immune system and at low doses may function as mild stress mimetics.
“The idea is that combining adaptogens into skin care can reinforce and support the skin’s resistance against stressors that can accelerate visible signs of aging,” said Dr. Shamban. “They share some similarities with antioxidants in that their main purpose is to protect the body from external stressors such as UV rays, oxidation, and pollution.” More studies should be conducted to verify effectiveness, she said, “but Eastern practices that have incorporated it for centuries shouldn’t be fully dismissed. Most doctors believe adaptogens are safe, but how they interact with the mechanics of the body’s stress response system remains a mystery.”
Embrace the consumption of micronutrients. Inspired by work from dermatologist Zoe Diana Draelos, MD, Dr. Shamban advises patients to eat a “rainbow of different colored foods” every day, especially those rich in vitamins A, C, and E. Green foods are generally rich in vitamin E, brown foods are rich in trace minerals, and blue/purple foods are rich in antioxidants. “It’s always best to get nutrients from a rich, healthy diet, but sometimes our skin requires extra help,” she said.
A randomized, placebo-controlled, double-blind study by French researchers, which showed that skin is prone to seasonal changes during the winter, particularly in exposed areas, also looked at whether a daily micronutrient supplement with ingredients that included green tea extract, blackcurrant seed oil, and magnesium, had an impact on the negative effects of winter weather on the skin. “The data indicate that oral micronutrient supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin,” she said.
Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.
AT MOAS 2022
FDA approves second antiamyloid for Alzheimer’s disease
Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.
Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.
“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.
“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.
Eisai has reported that lecanemab will cost $26,500 a year.
Modest benefit, adverse events
The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”
The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.
The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.
After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).
While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.
Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.
In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.
“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
Alzheimer’s Association reaction
Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.
In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.
“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.
“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.
After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”
Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”
“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
Critical issues
Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”
He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.
“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.
“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.
“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.
“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.
Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.
A version of this article first appeared on Medscape.com.
This article was updated 1/9/23.
Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.
Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.
“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.
“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.
Eisai has reported that lecanemab will cost $26,500 a year.
Modest benefit, adverse events
The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”
The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.
The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.
After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).
While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.
Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.
In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.
“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
Alzheimer’s Association reaction
Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.
In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.
“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.
“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.
After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”
Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”
“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
Critical issues
Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”
He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.
“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.
“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.
“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.
“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.
Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.
A version of this article first appeared on Medscape.com.
This article was updated 1/9/23.
Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.
Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.
“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.
“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.
Eisai has reported that lecanemab will cost $26,500 a year.
Modest benefit, adverse events
The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”
The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.
The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.
After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).
While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.
Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.
In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.
“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
Alzheimer’s Association reaction
Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.
In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.
“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.
“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.
After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”
Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”
“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
Critical issues
Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”
He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.
“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.
“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.
“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.
“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.
Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.
A version of this article first appeared on Medscape.com.
This article was updated 1/9/23.
Commentary: New Drugs, and Exercise, in Breast Cancer January 2023
This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.
A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.
Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.
Prior studies1 have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.
The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.
Additional References
Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival. J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046
This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.
A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.
Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.
Prior studies1 have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.
The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.
Additional References
Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival. J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046
This is the longest reported median PFS in HER2+ metastatic BC, highlighting the potential of trastuzumab deruxtecan in treating this disease and confirming this drug as the standard of care in the second-line setting.
A cohort study evaluated 315 postmenopausal BC survivors to estimate the association of physical activity with risk for all-cause mortality. Participants were queried about leisure-time physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), which provided a composite score that categorized exercise patterns as active, moderately active, or insufficiently active at baseline.
Results showed that participants who were active or moderately active had a 60% decreased risk for death compared with insufficiently active participants (active: HR 0.42 [95% CI 0.21-0.85]; moderately active: HR 0.40 [95% CI 0.17-0.95]). A similar mortality risk was reported among participants who were active and those with moderate physical activity levels.
Prior studies1 have reported similar results, reaffirming the value of exercise in BC survivors and highlighting the need to incorporate physical activity as part of survivorship care plans.
The phase 3 SOPHIA study randomized 536 patients with HER2+ advanced BC who had received two or more prior anti-HER2 regimens to margetuximab plus chemotherapy vs trastuzumab plus chemotherapy. Final OS results after a median follow-up of 20.2 months showed no benefit in OS observed with margetuximab vs trastuzumab (median OS 21.6 months vs 21.9 months; HR 0.95; P = .620). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients vs trastuzumab (median OS 23.6 vs 19.2 months; HR 0.72; 95% CI 0.52-1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients vs margetuximab (median OS 31.1 vs 22.0 months; HR 1.77; 95% CI 1.01–3.12). The safety profile of margetuximab was acceptable and comparable to that of trastuzumab. Further studies to evaluate the role of margetuximab in patients with HER2+ BC with different CD16A allelic variants are warranted.
Additional References
Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: Relationships with survival. J Natl Cancer Inst. 2021;113:54-63. Doi:10.1093/jnci/djaa046
Berdazimer gel under review at FDA for treating molluscum contagiosum
, the manufacturer announced.
If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.
The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.
The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.
The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.
, the manufacturer announced.
If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.
The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.
The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.
The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.
, the manufacturer announced.
If the submission is accepted by the FDA, the topical product could be approved in the first quarter of 2024, according to a press release from Novan, the manufacturer. If approved, it would be the first-in-class topical treatment for MC, the common, contagious viral skin infection that affects approximately six million individuals in the United States each year, most of them children aged 1-14 years, the statement noted. No FDA-approved therapies currently exist for the condition, which causes unsightly lesions on the face, trunk, limbs, and axillae that may persist untreated for a period of years.
The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a nitric oxide–releasing agent. A 3.4% formulation is in development for the topical treatment of acne, according to the company.
The submission for FDA approval is based on data from the B-SIMPLE4 study, a phase 3 randomized trial of nearly 900 individuals with MC aged 6 months and older (mean age, 6.6 years), with 3-70 raised lesions. Participants were randomized to treatment with berdazimer gel 10.3% or a vehicle gel applied in a thin layer to all lesions once daily for 12 weeks. The results were published in JAMA Dermatology.
The primary outcome was complete clearance of all lesions. At 12 weeks, 32.4% of patients in the berdazimer group achieved this outcome vs. 19.7% of those in the vehicle group (P < .001). Overall adverse event rates were low in both groups; 4.1% of patients on berdazimer and 0.7% of those on the vehicle experienced adverse events that led to discontinuation of treatment. The most common adverse events across both groups were application-site pain and erythema, and most of these were mild or moderate.
Latest steps toward reducing U.S. insulin cost begin in 2023
As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.
On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).
The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.
However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.
Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.
“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.
JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.
“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.
At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.
“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.
Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.
“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”
A version of this article first appeared on Medscape.com.
As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.
On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).
The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.
However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.
Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.
“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.
JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.
“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.
At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.
“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.
Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.
“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”
A version of this article first appeared on Medscape.com.
As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.
On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).
The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.
However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.
Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.
“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.
JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.
“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.
At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.
“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.
Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.
“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”
A version of this article first appeared on Medscape.com.
Gene associated with vision loss also linked to COVID: Study
age-related macular degeneration.
The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.
Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands.
“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.
Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.
A version of this article first appeared on WebMD.com.
age-related macular degeneration.
The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.
Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands.
“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.
Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.
A version of this article first appeared on WebMD.com.
age-related macular degeneration.
The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.
Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands.
“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.
Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.
A version of this article first appeared on WebMD.com.
FROM THE JOURNAL OF CLINICAL MEDICINE
Earlier colorectal cancer screening appears cost-effective in overweight, obese patients
Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.
In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.
Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.
“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”
The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and three strata of obesity – obese I (30 to <35 kg/m2), obese II (35 to <40 kg/m2), and obese III (>40 kg/m2).
For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.
For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.
Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.
For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.
Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.
Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.
FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.
Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.
Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.
“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”
The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.
Obesity is associated with an increased risk of colorectal cancer, along with cancers of the breast, endometrium, and esophagus. Even maternal obesity is associated with higher offspring colorectal cancer rates. Key mechanisms that underlie these associations include high insulin levels in obesity that propel tumor growth, adipose tissue that secretes inflammatory cytokines, and high glucose levels that act as fuel for cancer proliferation.
For men with BMI over 35, moving the colonoscopy screening age earlier to age 40 was cost-effective. However, it’s not clear that in practice the juice is worth the squeeze. Changing screening initiation times further based on personalized factors such as BMI could make screening more confusing for patients and physicians and may hurt uptake, a critical factor for the success of any screening program.
The study supports the current paradigm that screening starting at age 45 is cost-effective among men and women at all BMI ranges, a reassuring conclusion. It also serves as a sobering reminder that promoting metabolic health in our patients, our schools, and our communities is a valuable endeavor.
Sarah McGill, MD, MSc, FACG, FASGE, is associate professor medicine, gastroenterology, and hepatology at the University of North Carolina at Chapel Hill. She receives research funding from Olympus America, Finch Therapeutics, Genentech, Guardant Health, and Exact Sciences.
Obesity is associated with an increased risk of colorectal cancer, along with cancers of the breast, endometrium, and esophagus. Even maternal obesity is associated with higher offspring colorectal cancer rates. Key mechanisms that underlie these associations include high insulin levels in obesity that propel tumor growth, adipose tissue that secretes inflammatory cytokines, and high glucose levels that act as fuel for cancer proliferation.
For men with BMI over 35, moving the colonoscopy screening age earlier to age 40 was cost-effective. However, it’s not clear that in practice the juice is worth the squeeze. Changing screening initiation times further based on personalized factors such as BMI could make screening more confusing for patients and physicians and may hurt uptake, a critical factor for the success of any screening program.
The study supports the current paradigm that screening starting at age 45 is cost-effective among men and women at all BMI ranges, a reassuring conclusion. It also serves as a sobering reminder that promoting metabolic health in our patients, our schools, and our communities is a valuable endeavor.
Sarah McGill, MD, MSc, FACG, FASGE, is associate professor medicine, gastroenterology, and hepatology at the University of North Carolina at Chapel Hill. She receives research funding from Olympus America, Finch Therapeutics, Genentech, Guardant Health, and Exact Sciences.
Obesity is associated with an increased risk of colorectal cancer, along with cancers of the breast, endometrium, and esophagus. Even maternal obesity is associated with higher offspring colorectal cancer rates. Key mechanisms that underlie these associations include high insulin levels in obesity that propel tumor growth, adipose tissue that secretes inflammatory cytokines, and high glucose levels that act as fuel for cancer proliferation.
For men with BMI over 35, moving the colonoscopy screening age earlier to age 40 was cost-effective. However, it’s not clear that in practice the juice is worth the squeeze. Changing screening initiation times further based on personalized factors such as BMI could make screening more confusing for patients and physicians and may hurt uptake, a critical factor for the success of any screening program.
The study supports the current paradigm that screening starting at age 45 is cost-effective among men and women at all BMI ranges, a reassuring conclusion. It also serves as a sobering reminder that promoting metabolic health in our patients, our schools, and our communities is a valuable endeavor.
Sarah McGill, MD, MSc, FACG, FASGE, is associate professor medicine, gastroenterology, and hepatology at the University of North Carolina at Chapel Hill. She receives research funding from Olympus America, Finch Therapeutics, Genentech, Guardant Health, and Exact Sciences.
Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.
In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.
Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.
“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”
The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and three strata of obesity – obese I (30 to <35 kg/m2), obese II (35 to <40 kg/m2), and obese III (>40 kg/m2).
For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.
For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.
Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.
For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.
Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.
Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.
FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.
Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.
Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.
“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”
The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.
Starting colorectal cancer screening earlier than age 50 appears to be cost-effective for both men and women across all body mass index (BMI) measures, according to a study published in Clinical Gastroenterology and Hepatology.
In particular, colonoscopy is cost-effective at age 45 for all BMI strata and at age 40 in obese men. In addition, fecal immunochemical testing (FIT) is highly cost-effective at ages 40 or 45 for all BMI values, wrote Aaron Yeoh, MD, a gastroenterologist at the Stanford (Calif.) University, and colleagues.
Increased body fatness, defined as a high BMI, has increased sharply in recent decades and has been associated with a higher risk of colorectal cancer (CRC). Given the rising incidence of CRC in younger people, the American Cancer Society and U.S. Preventive Services Task Force now endorse screening at age 45. In previous analyses, Dr. Yeoh and colleagues suggested that the policy is likely to be cost-effective, but they didn’t explore the potential differences by BMI.
“Our results suggest that 45 years of age is a reasonable screening initiation age for women and men with BMI ranging from normal through all classes of obesity,” the authors wrote. “Before changing screening policy, supportive data from clinical studies would be needed. Our approach can be applied to future efforts aiming to risk-stratify CRC screening based on multiple clinical factors or biomarkers.”
The research team examined the potential effectiveness and cost-effectiveness of screening tailored to BMI starting as early as age 40 and ending at age 75 in 10 separate cohorts of men and women of normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and three strata of obesity – obese I (30 to <35 kg/m2), obese II (35 to <40 kg/m2), and obese III (>40 kg/m2).
For each cohort, the researchers estimated incremental costs per quality-adjusted life year (QALY) gained by initiating screening at age 40 versus age 45 versus age 50, or by shortening colonoscopy intervals. They modeled screening colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual FIT, offered from ages 40, 45, or 50 through age 75 with 100% adherence, with postpolypectomy surveillance through age 80.
For model inputs, the research team favored high-quality data from meta-analyses or large prospective trials. Screening, treatment, and complication costs were set at 2018 Centers for Medicare & Medicaid Services rates for ages 65 and older and modified to reflect commercial costs at ages 65 and younger. The authors assumed use of moderate sedation, and sensitivity analyses addressed possible increased costs and complications of colonoscopy under propofol.
Overall, without screening, sex-specific total CRC deaths were similar for people with overweight or obesity I-III and slightly higher than for people with normal BMI. For both men and women across all BMI strata, Colo10 or FIT starting at age 50 substantially decreased CRC incidence and mortality versus no screening, and the magnitude of the clinical impact was comparable across BMI.
For both sexes across BMI, Colo10 or FIT starting at age 50 was highly cost-effective. The cost per QALY gained for Colo10 compared with no screening became more favorable as BMI increased from normal to obesity III. FIT was cost-saving compared with no screening for all cohorts and was cost-saving or highly cost-effective compared with Colo10 within each cohort.
Initiating Colo10 at age 45 showed incremental decreases in CRC incidence and mortality, which were modest compared with the gains of Colo10 at age 50 versus no screening. However, the incremental gains were achieved at acceptable incremental costs ranging from $64,500 to $85,900 per QALY gained in women and from $33,400 to $64,200 per QALY gained in men.
Initiating Colo10 at age 40 in women and men in the lowest three BMI strata was associated with high incremental costs per QALY gained. In contrast, Colo10 initiation at age 40 cost $80,400 per QALY gained in men with obesity III and $93,300 per QALY gained in men with obesity II.
FIT starting at ages 40 or 45 yielded progressively greater decreases in CRC incidence and mortality for both men and women across BMI strata, and it was highly cost-effective versus starting at later ages. Compared with Colo10, at every screening initiation age, FIT was cost-saving or preferred based on very high incremental costs per QALY, and FIT required substantially fewer colonoscopies per person.
Intensifying screening by shortening the colonoscopy interval to Colo5 was never preferred over shifting Colo10 to earlier screening initiation ages. In all cohorts, Colo5 was either less effective and more costly than Colo10 at a younger age, or when it was more effective, the cost per QALY gained was substantially higher than $100,000 per QALY gained.
Additional studies are needed to understand obesity-specific colonoscopy risks and costs, the authors wrote. In addition, obesity is only one of several factors that should be considered when tailoring CRC screening to the level of CRC risk, they wrote.
“As the search for a multifactor prediction tool that is ready for clinical application continues, we face the question of how to approach single CRC risk factors such as obesity,” they wrote. “While screening guidelines based on BMI can be envisioned if supportive clinical data accumulate, clinical implementation must overcome operational challenges.”
The study funding was not disclosed. One author reported advisory and consultant roles for several medical companies, and the remaining authors disclosed no conflicts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY