Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

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

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

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

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

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

Much attention has been focused recently on the idea that breast cancer with a low expression of HER2 can be treated with HER2-targeted agents. Not surprisingly, manufacturers of these drugs have pounced on this idea, as it opens up a whole new patient population: previously these drugs were only for tumors with a high HER2 expression.

There is a large potential market at stake: HER2-low (also referred to as ERBB2-low), as defined by a score of 0 to 3+ on immunohistochemistry (IHC), is seen in approximately 50%-60% of all breast cancers

However, there is still much debate over whether low-HER2 breast cancer is, in fact, a separate clinical entity.

A new large-scale analysis concludes that it is not. The authors argued that it actually it represents a series of biological differences from HER2-negative disease that do not have a strong bearing on outcomes.

The analysis was published online in JAMA Oncology.

For the study, researchers from the University of Chicago examined data on more than 1.1 million breast cancer patients recorded as HER2-negative in the U.S. National Cancer Database, and re-classified almost two thirds as HER2-low on further analysis.

They found that HER2-low status was associated with higher estrogen receptor (ER) expression, as well as a lower rate of pathologic complete response, compared with HER2-negative disease. It was also linked to an improvement in overall survival on multivariate analysis of up to 9% in advance stage triple negative tumors.

“However, the clinical significance of these differences is questionable,” the researchers commented.

HER2-low status alone “should not influence neoadjuvant treatment decisions with currently approved regimens,” they added.

These results “do not support classification of HER2-low breast cancer as a distinct clinical subtype,” the team concluded.

Not necessarily, according to Giuseppe Curigliano, MD, PhD, director of the new drugs and early drug development for innovative therapies division at the European Institute of Oncology, Milan. He argued the opposite case, that HER2-low is a separate clinical entity, in a recent debate on the topic held at the 2022 San Antonio Breast Cancer Symposium.

In a comment, Dr. Curigliano said that a “major strength” of the current study is its large patient cohort, which reflects the majority of cancer diagnoses in the United States, but that it nevertheless has “important limitations that should be considered when interpreting the results.”

The inclusion of only overall survival in the dataset limits the ability to make associations between HER2-low status and cancer-specific prognosis, as “survival may lag years behind recurrence.”

The lack of centralized assessment of IHC results is also an issue, as “some of the results may be associated with regional variation in practice of classifying cases as HER2 0 versus HER2 1+.”

“In my opinion, this is a great limitation,” he said, in being able to conclude that there is “no prognostic difference between ERBB2-low and -negative patients.”

He also noted that, from a molecular point of view, “the key determinant of the gene expression profile is the expression of hormone receptors, [and] if we perform a correction for hormone receptor expression, only marginal differences in gene expression are found” between HER2-low and HER2-negative tumors.

“Similarly, large genomic studies have identified no specific and consistent difference in genomic profiles,” Dr. Curigliano said, and so, HER2-low disease, “as currently defined, should not be considered a distinct molecular entity, but rather a heterogeneous group of tumors, with biology primarily driven by hormone receptor expression.”
 

Analysis quoted by both sides

Senior author of the new analysis, Frederick M. Howard, MD, from the section of hematology-oncology in the department of medicine at the University of Chicago, said that his team’s work was quoted by both sides of the debate at SABCS 2022.

This reflects the fact that, while differences between ERBB2-low and -negative are present, it is “questionable how clinically significant those differences are,” he said in an interview. It’s a matter of “the eye of the beholder.”

Dr. Howard does not think that clinicians are going to modify standard treatment regimens based solely on HER2-low status, and that low expression of the protein “is probably just a reflection of some underlying biologic processes.”

Dr. Howard agreed with Dr. Curigliano that a “caveat” of their study is that the IHC analyses were performed locally, especially as it has shown that there can be discordance between pathologists in around 40% of cases, and that the associations they found might therefore be “strengthened” by more precise quantification of HER2 expression.

“But, even then,” Dr. Howard continued, “I doubt that [ERBB2-low status] is going to be that strong a prognostic factor.”

He believes that advances in analytic techniques will, in the future, allow tumors to be characterized more precisely, and it may be that HER2-low tumors end up being called something else in 5 years.
 

Renewed interest in this subgroup

In their paper, Dr. Howard and colleagues pointed out that, as a group, HER2-low tumors are heterogeneous, with HER2-low found in both hormone receptor–positive and triple-negative breast cancers. Also, various studies have come to different conclusions about what HER2 low means prognostically, with conclusions ranging from negative to neutral and to positive prognoses.

However, new research has shown that patients with HER2-low tumors can benefit from HER2-targeted drugs. In particular, the recent report that the antibody-drug conjugate trastuzumab deruxtecan doubled progression-free survival versus chemotherapy in ERBB2-low tumors led to “renewed interest in the subgroup,” the researchers noted.

To examine this subgroup further, they embarked on their analysis. Examining the National Cancer Database, they gathered information on more than 1.1 million U.S. patients diagnosed with HER2-negative invasive breast cancer in the 10-year period 2010-2019, and for whom IHC results were available.

The patients were reclassified as having HER2-low disease if they had an IHC score of 1+, or 2+ with a negative in situ hybridization test, while those with an IHC score of 0 were deemed to be HER2-negative. They were followed up until Nov. 30, 2022.

These patients had a mean age of 62.4 years, and 99.1% were female. The majority (78.6%) were non-Hispanic white. HER2-low was identified in 65.5% of the cohort, while 34.5% were HER2-negative.

The proportion of HER2-low disease was lower in non-Hispanic black (62.8%) and Hispanic (61%) patients than in non-Hispanic White patients, at 66.1%.

HER2-low disease was also more common in hormone receptor–positive than triple-negative tumors, at just 51.5%, rising to 58.6% for progesterone receptor–positive, ER-negative, and 69.1% for PR-positive, ER-positive tumors.

Multivariate logistic regression analysis taking into account age, sex, race and ethnicity, comorbidity score, and treatment facility type, among other factors, revealed that the likelihood of HER2-low disease was significantly with increased ER expression, at an adjusted odds ratio of 1.15 for each 10% increase (P < .001).

Non-Hispanic Black, Asian, and Pacific Islander patients had similar rates of HER2-low disease as non-Hispanic White patients after adjustment, whereas Native American patients had an increased rate, at an aOR of 1.22 (P < .001), and Hispanic patients had a lower rate, at an aOR of 0.85 (P < .001).

HER2-low status was associated with a slightly reduced likelihood of having a pathologic complete response (aOR, 0.89; P < .001), with similar results when restricting the analysis to patients with triple negative or hormone receptor-positive tumors.

After a median follow-up of 54 months, HER2-low disease was associated with a minor improvement in survival on multivariate analysis, at an adjusted hazard ratio for death of 0.98 (P < .001).

The greatest improvement in survival was seen in patients with stage III and IV triple-negative breast cancer, at HRs of 0.92 and 0.91, respectively, although the researchers noted that this represented only a 2% and 0.4% improvement in 5-year overall survival, respectively.

The study was supported by the Breast Cancer Research Foundation, the American Society of Clinical Oncology/Conquer Cancer Foundation, the Department of Defense, the National Institutes of Health/National Cancer Institute, Susan G. Komen, the Breast Cancer Research Foundation, and the University of Chicago Elwood V. Jensen Scholars Program. Dr. Howard reported no relevant financial relationships. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, Veracyte, Daiichi Sankyo, AstraZeneca, Merck, Seagen, Exact Sciences, Gilead, Bristol-Myers Squibb, Scientific Affairs Group, and Ellipsis.

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

Much attention has been focused recently on the idea that breast cancer with a low expression of HER2 can be treated with HER2-targeted agents. Not surprisingly, manufacturers of these drugs have pounced on this idea, as it opens up a whole new patient population: previously these drugs were only for tumors with a high HER2 expression.

There is a large potential market at stake: HER2-low (also referred to as ERBB2-low), as defined by a score of 0 to 3+ on immunohistochemistry (IHC), is seen in approximately 50%-60% of all breast cancers

However, there is still much debate over whether low-HER2 breast cancer is, in fact, a separate clinical entity.

A new large-scale analysis concludes that it is not. The authors argued that it actually it represents a series of biological differences from HER2-negative disease that do not have a strong bearing on outcomes.

The analysis was published online in JAMA Oncology.

For the study, researchers from the University of Chicago examined data on more than 1.1 million breast cancer patients recorded as HER2-negative in the U.S. National Cancer Database, and re-classified almost two thirds as HER2-low on further analysis.

They found that HER2-low status was associated with higher estrogen receptor (ER) expression, as well as a lower rate of pathologic complete response, compared with HER2-negative disease. It was also linked to an improvement in overall survival on multivariate analysis of up to 9% in advance stage triple negative tumors.

“However, the clinical significance of these differences is questionable,” the researchers commented.

HER2-low status alone “should not influence neoadjuvant treatment decisions with currently approved regimens,” they added.

These results “do not support classification of HER2-low breast cancer as a distinct clinical subtype,” the team concluded.

Not necessarily, according to Giuseppe Curigliano, MD, PhD, director of the new drugs and early drug development for innovative therapies division at the European Institute of Oncology, Milan. He argued the opposite case, that HER2-low is a separate clinical entity, in a recent debate on the topic held at the 2022 San Antonio Breast Cancer Symposium.

In a comment, Dr. Curigliano said that a “major strength” of the current study is its large patient cohort, which reflects the majority of cancer diagnoses in the United States, but that it nevertheless has “important limitations that should be considered when interpreting the results.”

The inclusion of only overall survival in the dataset limits the ability to make associations between HER2-low status and cancer-specific prognosis, as “survival may lag years behind recurrence.”

The lack of centralized assessment of IHC results is also an issue, as “some of the results may be associated with regional variation in practice of classifying cases as HER2 0 versus HER2 1+.”

“In my opinion, this is a great limitation,” he said, in being able to conclude that there is “no prognostic difference between ERBB2-low and -negative patients.”

He also noted that, from a molecular point of view, “the key determinant of the gene expression profile is the expression of hormone receptors, [and] if we perform a correction for hormone receptor expression, only marginal differences in gene expression are found” between HER2-low and HER2-negative tumors.

“Similarly, large genomic studies have identified no specific and consistent difference in genomic profiles,” Dr. Curigliano said, and so, HER2-low disease, “as currently defined, should not be considered a distinct molecular entity, but rather a heterogeneous group of tumors, with biology primarily driven by hormone receptor expression.”
 

Analysis quoted by both sides

Senior author of the new analysis, Frederick M. Howard, MD, from the section of hematology-oncology in the department of medicine at the University of Chicago, said that his team’s work was quoted by both sides of the debate at SABCS 2022.

This reflects the fact that, while differences between ERBB2-low and -negative are present, it is “questionable how clinically significant those differences are,” he said in an interview. It’s a matter of “the eye of the beholder.”

Dr. Howard does not think that clinicians are going to modify standard treatment regimens based solely on HER2-low status, and that low expression of the protein “is probably just a reflection of some underlying biologic processes.”

Dr. Howard agreed with Dr. Curigliano that a “caveat” of their study is that the IHC analyses were performed locally, especially as it has shown that there can be discordance between pathologists in around 40% of cases, and that the associations they found might therefore be “strengthened” by more precise quantification of HER2 expression.

“But, even then,” Dr. Howard continued, “I doubt that [ERBB2-low status] is going to be that strong a prognostic factor.”

He believes that advances in analytic techniques will, in the future, allow tumors to be characterized more precisely, and it may be that HER2-low tumors end up being called something else in 5 years.
 

Renewed interest in this subgroup

In their paper, Dr. Howard and colleagues pointed out that, as a group, HER2-low tumors are heterogeneous, with HER2-low found in both hormone receptor–positive and triple-negative breast cancers. Also, various studies have come to different conclusions about what HER2 low means prognostically, with conclusions ranging from negative to neutral and to positive prognoses.

However, new research has shown that patients with HER2-low tumors can benefit from HER2-targeted drugs. In particular, the recent report that the antibody-drug conjugate trastuzumab deruxtecan doubled progression-free survival versus chemotherapy in ERBB2-low tumors led to “renewed interest in the subgroup,” the researchers noted.

To examine this subgroup further, they embarked on their analysis. Examining the National Cancer Database, they gathered information on more than 1.1 million U.S. patients diagnosed with HER2-negative invasive breast cancer in the 10-year period 2010-2019, and for whom IHC results were available.

The patients were reclassified as having HER2-low disease if they had an IHC score of 1+, or 2+ with a negative in situ hybridization test, while those with an IHC score of 0 were deemed to be HER2-negative. They were followed up until Nov. 30, 2022.

These patients had a mean age of 62.4 years, and 99.1% were female. The majority (78.6%) were non-Hispanic white. HER2-low was identified in 65.5% of the cohort, while 34.5% were HER2-negative.

The proportion of HER2-low disease was lower in non-Hispanic black (62.8%) and Hispanic (61%) patients than in non-Hispanic White patients, at 66.1%.

HER2-low disease was also more common in hormone receptor–positive than triple-negative tumors, at just 51.5%, rising to 58.6% for progesterone receptor–positive, ER-negative, and 69.1% for PR-positive, ER-positive tumors.

Multivariate logistic regression analysis taking into account age, sex, race and ethnicity, comorbidity score, and treatment facility type, among other factors, revealed that the likelihood of HER2-low disease was significantly with increased ER expression, at an adjusted odds ratio of 1.15 for each 10% increase (P < .001).

Non-Hispanic Black, Asian, and Pacific Islander patients had similar rates of HER2-low disease as non-Hispanic White patients after adjustment, whereas Native American patients had an increased rate, at an aOR of 1.22 (P < .001), and Hispanic patients had a lower rate, at an aOR of 0.85 (P < .001).

HER2-low status was associated with a slightly reduced likelihood of having a pathologic complete response (aOR, 0.89; P < .001), with similar results when restricting the analysis to patients with triple negative or hormone receptor-positive tumors.

After a median follow-up of 54 months, HER2-low disease was associated with a minor improvement in survival on multivariate analysis, at an adjusted hazard ratio for death of 0.98 (P < .001).

The greatest improvement in survival was seen in patients with stage III and IV triple-negative breast cancer, at HRs of 0.92 and 0.91, respectively, although the researchers noted that this represented only a 2% and 0.4% improvement in 5-year overall survival, respectively.

The study was supported by the Breast Cancer Research Foundation, the American Society of Clinical Oncology/Conquer Cancer Foundation, the Department of Defense, the National Institutes of Health/National Cancer Institute, Susan G. Komen, the Breast Cancer Research Foundation, and the University of Chicago Elwood V. Jensen Scholars Program. Dr. Howard reported no relevant financial relationships. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, Veracyte, Daiichi Sankyo, AstraZeneca, Merck, Seagen, Exact Sciences, Gilead, Bristol-Myers Squibb, Scientific Affairs Group, and Ellipsis.

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

Much attention has been focused recently on the idea that breast cancer with a low expression of HER2 can be treated with HER2-targeted agents. Not surprisingly, manufacturers of these drugs have pounced on this idea, as it opens up a whole new patient population: previously these drugs were only for tumors with a high HER2 expression.

There is a large potential market at stake: HER2-low (also referred to as ERBB2-low), as defined by a score of 0 to 3+ on immunohistochemistry (IHC), is seen in approximately 50%-60% of all breast cancers

However, there is still much debate over whether low-HER2 breast cancer is, in fact, a separate clinical entity.

A new large-scale analysis concludes that it is not. The authors argued that it actually it represents a series of biological differences from HER2-negative disease that do not have a strong bearing on outcomes.

The analysis was published online in JAMA Oncology.

For the study, researchers from the University of Chicago examined data on more than 1.1 million breast cancer patients recorded as HER2-negative in the U.S. National Cancer Database, and re-classified almost two thirds as HER2-low on further analysis.

They found that HER2-low status was associated with higher estrogen receptor (ER) expression, as well as a lower rate of pathologic complete response, compared with HER2-negative disease. It was also linked to an improvement in overall survival on multivariate analysis of up to 9% in advance stage triple negative tumors.

“However, the clinical significance of these differences is questionable,” the researchers commented.

HER2-low status alone “should not influence neoadjuvant treatment decisions with currently approved regimens,” they added.

These results “do not support classification of HER2-low breast cancer as a distinct clinical subtype,” the team concluded.

Not necessarily, according to Giuseppe Curigliano, MD, PhD, director of the new drugs and early drug development for innovative therapies division at the European Institute of Oncology, Milan. He argued the opposite case, that HER2-low is a separate clinical entity, in a recent debate on the topic held at the 2022 San Antonio Breast Cancer Symposium.

In a comment, Dr. Curigliano said that a “major strength” of the current study is its large patient cohort, which reflects the majority of cancer diagnoses in the United States, but that it nevertheless has “important limitations that should be considered when interpreting the results.”

The inclusion of only overall survival in the dataset limits the ability to make associations between HER2-low status and cancer-specific prognosis, as “survival may lag years behind recurrence.”

The lack of centralized assessment of IHC results is also an issue, as “some of the results may be associated with regional variation in practice of classifying cases as HER2 0 versus HER2 1+.”

“In my opinion, this is a great limitation,” he said, in being able to conclude that there is “no prognostic difference between ERBB2-low and -negative patients.”

He also noted that, from a molecular point of view, “the key determinant of the gene expression profile is the expression of hormone receptors, [and] if we perform a correction for hormone receptor expression, only marginal differences in gene expression are found” between HER2-low and HER2-negative tumors.

“Similarly, large genomic studies have identified no specific and consistent difference in genomic profiles,” Dr. Curigliano said, and so, HER2-low disease, “as currently defined, should not be considered a distinct molecular entity, but rather a heterogeneous group of tumors, with biology primarily driven by hormone receptor expression.”
 

Analysis quoted by both sides

Senior author of the new analysis, Frederick M. Howard, MD, from the section of hematology-oncology in the department of medicine at the University of Chicago, said that his team’s work was quoted by both sides of the debate at SABCS 2022.

This reflects the fact that, while differences between ERBB2-low and -negative are present, it is “questionable how clinically significant those differences are,” he said in an interview. It’s a matter of “the eye of the beholder.”

Dr. Howard does not think that clinicians are going to modify standard treatment regimens based solely on HER2-low status, and that low expression of the protein “is probably just a reflection of some underlying biologic processes.”

Dr. Howard agreed with Dr. Curigliano that a “caveat” of their study is that the IHC analyses were performed locally, especially as it has shown that there can be discordance between pathologists in around 40% of cases, and that the associations they found might therefore be “strengthened” by more precise quantification of HER2 expression.

“But, even then,” Dr. Howard continued, “I doubt that [ERBB2-low status] is going to be that strong a prognostic factor.”

He believes that advances in analytic techniques will, in the future, allow tumors to be characterized more precisely, and it may be that HER2-low tumors end up being called something else in 5 years.
 

Renewed interest in this subgroup

In their paper, Dr. Howard and colleagues pointed out that, as a group, HER2-low tumors are heterogeneous, with HER2-low found in both hormone receptor–positive and triple-negative breast cancers. Also, various studies have come to different conclusions about what HER2 low means prognostically, with conclusions ranging from negative to neutral and to positive prognoses.

However, new research has shown that patients with HER2-low tumors can benefit from HER2-targeted drugs. In particular, the recent report that the antibody-drug conjugate trastuzumab deruxtecan doubled progression-free survival versus chemotherapy in ERBB2-low tumors led to “renewed interest in the subgroup,” the researchers noted.

To examine this subgroup further, they embarked on their analysis. Examining the National Cancer Database, they gathered information on more than 1.1 million U.S. patients diagnosed with HER2-negative invasive breast cancer in the 10-year period 2010-2019, and for whom IHC results were available.

The patients were reclassified as having HER2-low disease if they had an IHC score of 1+, or 2+ with a negative in situ hybridization test, while those with an IHC score of 0 were deemed to be HER2-negative. They were followed up until Nov. 30, 2022.

These patients had a mean age of 62.4 years, and 99.1% were female. The majority (78.6%) were non-Hispanic white. HER2-low was identified in 65.5% of the cohort, while 34.5% were HER2-negative.

The proportion of HER2-low disease was lower in non-Hispanic black (62.8%) and Hispanic (61%) patients than in non-Hispanic White patients, at 66.1%.

HER2-low disease was also more common in hormone receptor–positive than triple-negative tumors, at just 51.5%, rising to 58.6% for progesterone receptor–positive, ER-negative, and 69.1% for PR-positive, ER-positive tumors.

Multivariate logistic regression analysis taking into account age, sex, race and ethnicity, comorbidity score, and treatment facility type, among other factors, revealed that the likelihood of HER2-low disease was significantly with increased ER expression, at an adjusted odds ratio of 1.15 for each 10% increase (P < .001).

Non-Hispanic Black, Asian, and Pacific Islander patients had similar rates of HER2-low disease as non-Hispanic White patients after adjustment, whereas Native American patients had an increased rate, at an aOR of 1.22 (P < .001), and Hispanic patients had a lower rate, at an aOR of 0.85 (P < .001).

HER2-low status was associated with a slightly reduced likelihood of having a pathologic complete response (aOR, 0.89; P < .001), with similar results when restricting the analysis to patients with triple negative or hormone receptor-positive tumors.

After a median follow-up of 54 months, HER2-low disease was associated with a minor improvement in survival on multivariate analysis, at an adjusted hazard ratio for death of 0.98 (P < .001).

The greatest improvement in survival was seen in patients with stage III and IV triple-negative breast cancer, at HRs of 0.92 and 0.91, respectively, although the researchers noted that this represented only a 2% and 0.4% improvement in 5-year overall survival, respectively.

The study was supported by the Breast Cancer Research Foundation, the American Society of Clinical Oncology/Conquer Cancer Foundation, the Department of Defense, the National Institutes of Health/National Cancer Institute, Susan G. Komen, the Breast Cancer Research Foundation, and the University of Chicago Elwood V. Jensen Scholars Program. Dr. Howard reported no relevant financial relationships. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, Veracyte, Daiichi Sankyo, AstraZeneca, Merck, Seagen, Exact Sciences, Gilead, Bristol-Myers Squibb, Scientific Affairs Group, and Ellipsis.

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

The Food and Drug Administration has expanded the indication for adjuvant abemaciclib (Verzenio) in combination with endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer who are at high risk for recurrence.

Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.

The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.

At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.

“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.

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

The Food and Drug Administration has expanded the indication for adjuvant abemaciclib (Verzenio) in combination with endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer who are at high risk for recurrence.

Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.

The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.

At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.

“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.

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

The Food and Drug Administration has expanded the indication for adjuvant abemaciclib (Verzenio) in combination with endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer who are at high risk for recurrence.

Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.

The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.

At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.

“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.

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

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

AGA offers guidance on celiac disease to help patients maintain a gluten-free diet in the AGA GI Patient Center: www.gastro.org/celiac .

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

AGA offers guidance on celiac disease to help patients maintain a gluten-free diet in the AGA GI Patient Center: www.gastro.org/celiac .

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

AGA offers guidance on celiac disease to help patients maintain a gluten-free diet in the AGA GI Patient Center: www.gastro.org/celiac .

Following a fish-based pescatarian diet or plant-based vegetarian or vegan diet is associated with not only the greatest benefit to health but also the lowest impact on the environment, suggests a new analysis that reveals meat-based, as well as keto and paleo diets, to be the worst on both measures.

The research was published online in The American Journal of Clinical Nutrition.

To obtain a real-world view on the environmental and health impact of diets as consumed by U.S. adults, the team examined a nationally representative survey of the 1-day eating habits of more than 16,000 individuals.

This revealed that the best quality diet was pescatarian, followed by vegetarian and vegan diets. Omnivore diets, although less healthy, tended to score better than keto and paleo diets, which were the lowest ranked.

Both keto and paleo diets tend to be higher in animal foods and lower in plant foods than other popular diets, the researchers explain in their study, and they both have been associated with negative effects on blood lipids, specifically increased LDL cholesterol, raising concern about the long-term health outcomes associated with these diets.”

Analysis of the environmental impact of the different eating patterns showed that the vegan diet had the lowest carbon footprint, followed by the vegetarian and pescatarian diets. The omnivore, paleo, and keto diets had a far higher carbon footprint, with that of the keto diet more than four times greater than that for a vegan diet.

“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant-based diet,” said senior author Diego Rose, PhD, MPH, RD, in a press release.

“Based on our results, that would reduce your footprint and be generally healthy,” noted Dr. Rose, nutrition program director, Tulane University, New Orleans.

To determine the carbon footprint and quality of popular diets as they are consumed by U.S. adults, Keelia O’Malley, PhD, MPH, Amelia Willits-Smith, PhD, MSc, and Dr. Rose, all with Tulane University, studied 24-hour recall data from the ongoing, nationally representative National Health and Nutrition Examination Survey (NHANES) for the years 2005-2010.

The data, which was captured by trained interviewers using a validated tool, was matched with the U.S. Department of Agriculture Food Patterns Equivalents Database to categorize the participants into one of six mutually exclusive categories: vegan, vegetarian, pescatarian, keto, paleo, or omnivore.

The omnivore category included anyone who did not fit into any of the preceding categories.

The environmental impact of the diets was then calculated by matching the established greenhouse gas emissions (GHGE) of over 300 commodities to foods listed on the NHANES, which was then summarized for each individual to give a carbon footprint for their 1-day diet.

Finally, the quality of their diet was estimated using the 2010 versions of the Healthy Eating Index and the Alternate Healthy Eating Index, both of which award a score to food components based on their impact on health.

Overall, 16,412 individuals were included in the analysis, of whom 52.1% were female.

The most common diet was omnivore, which was followed by 83.6% of respondents, followed by vegetarian (7.5%), pescatarian (4.7%), vegan (0.7%), keto (0.4%), and paleo diets (0.3%).

The lowest carbon footprint was seen with a vegan diet, at an average of 0.69 kg of carbon dioxide equivalents per 1,000 kcal consumed, followed by a vegetarian diet (1.16 kg of carbon dioxide equivalents per 1,000 kcal) and pescatarian diet (1.66 kg of carbon dioxide equivalents per 1,000 kcal).

The highest carbon footprints were observed with the omnivore (2.23 kg of carbon dioxide equivalents per 1,000 kcal), paleo (2.62 kg of carbon dioxide equivalents per 1,000 kcal), and keto diets (2.91 kg of carbon dioxide equivalents per 1,000 kcal).

In terms of diet quality, the pescatarian diet was ranked the highest on both eating index scores, followed by the vegetarian, then vegan, diets. The order of the three lowest scores depended on the index used, with either the keto or paleo diet deemed to be the worst quality.

Analysis of individuals following an omnivore diet suggested that those who ate in line with the DASH or Mediterranean diets had higher diet quality, as well as a lower environmental impact, than other people within the group.

Hence, Dr. Rose observed, “Our research ... shows there is a way to improve your health and footprint without giving up meat entirely.”

The researchers acknowledge that the use of 1-day diets has limitations, including that whatever individuals may have eaten during those 24 hours may not correspond to their overall day-in, day-out diet.

The study was supported by the Wellcome Trust. Dr. Rose declares relationships with the Center for Biological Diversity, the NCI, and the Health Resources and Services Administration. Dr. Willits-Smith has received funding from CBD and NCI. Dr. O’Malley has received funding from HRSA.

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

Following a fish-based pescatarian diet or plant-based vegetarian or vegan diet is associated with not only the greatest benefit to health but also the lowest impact on the environment, suggests a new analysis that reveals meat-based, as well as keto and paleo diets, to be the worst on both measures.

The research was published online in The American Journal of Clinical Nutrition.

To obtain a real-world view on the environmental and health impact of diets as consumed by U.S. adults, the team examined a nationally representative survey of the 1-day eating habits of more than 16,000 individuals.

This revealed that the best quality diet was pescatarian, followed by vegetarian and vegan diets. Omnivore diets, although less healthy, tended to score better than keto and paleo diets, which were the lowest ranked.

Both keto and paleo diets tend to be higher in animal foods and lower in plant foods than other popular diets, the researchers explain in their study, and they both have been associated with negative effects on blood lipids, specifically increased LDL cholesterol, raising concern about the long-term health outcomes associated with these diets.”

Analysis of the environmental impact of the different eating patterns showed that the vegan diet had the lowest carbon footprint, followed by the vegetarian and pescatarian diets. The omnivore, paleo, and keto diets had a far higher carbon footprint, with that of the keto diet more than four times greater than that for a vegan diet.

“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant-based diet,” said senior author Diego Rose, PhD, MPH, RD, in a press release.

“Based on our results, that would reduce your footprint and be generally healthy,” noted Dr. Rose, nutrition program director, Tulane University, New Orleans.

To determine the carbon footprint and quality of popular diets as they are consumed by U.S. adults, Keelia O’Malley, PhD, MPH, Amelia Willits-Smith, PhD, MSc, and Dr. Rose, all with Tulane University, studied 24-hour recall data from the ongoing, nationally representative National Health and Nutrition Examination Survey (NHANES) for the years 2005-2010.

The data, which was captured by trained interviewers using a validated tool, was matched with the U.S. Department of Agriculture Food Patterns Equivalents Database to categorize the participants into one of six mutually exclusive categories: vegan, vegetarian, pescatarian, keto, paleo, or omnivore.

The omnivore category included anyone who did not fit into any of the preceding categories.

The environmental impact of the diets was then calculated by matching the established greenhouse gas emissions (GHGE) of over 300 commodities to foods listed on the NHANES, which was then summarized for each individual to give a carbon footprint for their 1-day diet.

Finally, the quality of their diet was estimated using the 2010 versions of the Healthy Eating Index and the Alternate Healthy Eating Index, both of which award a score to food components based on their impact on health.

Overall, 16,412 individuals were included in the analysis, of whom 52.1% were female.

The most common diet was omnivore, which was followed by 83.6% of respondents, followed by vegetarian (7.5%), pescatarian (4.7%), vegan (0.7%), keto (0.4%), and paleo diets (0.3%).

The lowest carbon footprint was seen with a vegan diet, at an average of 0.69 kg of carbon dioxide equivalents per 1,000 kcal consumed, followed by a vegetarian diet (1.16 kg of carbon dioxide equivalents per 1,000 kcal) and pescatarian diet (1.66 kg of carbon dioxide equivalents per 1,000 kcal).

The highest carbon footprints were observed with the omnivore (2.23 kg of carbon dioxide equivalents per 1,000 kcal), paleo (2.62 kg of carbon dioxide equivalents per 1,000 kcal), and keto diets (2.91 kg of carbon dioxide equivalents per 1,000 kcal).

In terms of diet quality, the pescatarian diet was ranked the highest on both eating index scores, followed by the vegetarian, then vegan, diets. The order of the three lowest scores depended on the index used, with either the keto or paleo diet deemed to be the worst quality.

Analysis of individuals following an omnivore diet suggested that those who ate in line with the DASH or Mediterranean diets had higher diet quality, as well as a lower environmental impact, than other people within the group.

Hence, Dr. Rose observed, “Our research ... shows there is a way to improve your health and footprint without giving up meat entirely.”

The researchers acknowledge that the use of 1-day diets has limitations, including that whatever individuals may have eaten during those 24 hours may not correspond to their overall day-in, day-out diet.

The study was supported by the Wellcome Trust. Dr. Rose declares relationships with the Center for Biological Diversity, the NCI, and the Health Resources and Services Administration. Dr. Willits-Smith has received funding from CBD and NCI. Dr. O’Malley has received funding from HRSA.

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

Following a fish-based pescatarian diet or plant-based vegetarian or vegan diet is associated with not only the greatest benefit to health but also the lowest impact on the environment, suggests a new analysis that reveals meat-based, as well as keto and paleo diets, to be the worst on both measures.

The research was published online in The American Journal of Clinical Nutrition.

To obtain a real-world view on the environmental and health impact of diets as consumed by U.S. adults, the team examined a nationally representative survey of the 1-day eating habits of more than 16,000 individuals.

This revealed that the best quality diet was pescatarian, followed by vegetarian and vegan diets. Omnivore diets, although less healthy, tended to score better than keto and paleo diets, which were the lowest ranked.

Both keto and paleo diets tend to be higher in animal foods and lower in plant foods than other popular diets, the researchers explain in their study, and they both have been associated with negative effects on blood lipids, specifically increased LDL cholesterol, raising concern about the long-term health outcomes associated with these diets.”

Analysis of the environmental impact of the different eating patterns showed that the vegan diet had the lowest carbon footprint, followed by the vegetarian and pescatarian diets. The omnivore, paleo, and keto diets had a far higher carbon footprint, with that of the keto diet more than four times greater than that for a vegan diet.

“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant-based diet,” said senior author Diego Rose, PhD, MPH, RD, in a press release.

“Based on our results, that would reduce your footprint and be generally healthy,” noted Dr. Rose, nutrition program director, Tulane University, New Orleans.

To determine the carbon footprint and quality of popular diets as they are consumed by U.S. adults, Keelia O’Malley, PhD, MPH, Amelia Willits-Smith, PhD, MSc, and Dr. Rose, all with Tulane University, studied 24-hour recall data from the ongoing, nationally representative National Health and Nutrition Examination Survey (NHANES) for the years 2005-2010.

The data, which was captured by trained interviewers using a validated tool, was matched with the U.S. Department of Agriculture Food Patterns Equivalents Database to categorize the participants into one of six mutually exclusive categories: vegan, vegetarian, pescatarian, keto, paleo, or omnivore.

The omnivore category included anyone who did not fit into any of the preceding categories.

The environmental impact of the diets was then calculated by matching the established greenhouse gas emissions (GHGE) of over 300 commodities to foods listed on the NHANES, which was then summarized for each individual to give a carbon footprint for their 1-day diet.

Finally, the quality of their diet was estimated using the 2010 versions of the Healthy Eating Index and the Alternate Healthy Eating Index, both of which award a score to food components based on their impact on health.

Overall, 16,412 individuals were included in the analysis, of whom 52.1% were female.

The most common diet was omnivore, which was followed by 83.6% of respondents, followed by vegetarian (7.5%), pescatarian (4.7%), vegan (0.7%), keto (0.4%), and paleo diets (0.3%).

The lowest carbon footprint was seen with a vegan diet, at an average of 0.69 kg of carbon dioxide equivalents per 1,000 kcal consumed, followed by a vegetarian diet (1.16 kg of carbon dioxide equivalents per 1,000 kcal) and pescatarian diet (1.66 kg of carbon dioxide equivalents per 1,000 kcal).

The highest carbon footprints were observed with the omnivore (2.23 kg of carbon dioxide equivalents per 1,000 kcal), paleo (2.62 kg of carbon dioxide equivalents per 1,000 kcal), and keto diets (2.91 kg of carbon dioxide equivalents per 1,000 kcal).

In terms of diet quality, the pescatarian diet was ranked the highest on both eating index scores, followed by the vegetarian, then vegan, diets. The order of the three lowest scores depended on the index used, with either the keto or paleo diet deemed to be the worst quality.

Analysis of individuals following an omnivore diet suggested that those who ate in line with the DASH or Mediterranean diets had higher diet quality, as well as a lower environmental impact, than other people within the group.

Hence, Dr. Rose observed, “Our research ... shows there is a way to improve your health and footprint without giving up meat entirely.”

The researchers acknowledge that the use of 1-day diets has limitations, including that whatever individuals may have eaten during those 24 hours may not correspond to their overall day-in, day-out diet.

The study was supported by the Wellcome Trust. Dr. Rose declares relationships with the Center for Biological Diversity, the NCI, and the Health Resources and Services Administration. Dr. Willits-Smith has received funding from CBD and NCI. Dr. O’Malley has received funding from HRSA.

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

Drinking a no-or low-calorie nonnutritive sweetened (NNS) beverage was no different from drinking water in terms of effect on 2-hour postprandial levels of glucose and hormones related to appetite or food intake.

Drinking a sugar-sweetened beverage (SSB), however, had a different effect on postprandial levels of glucose and the hormones insulin, glucagonlike peptide–1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon.

These findings are from a new meta-analysis by Roselyn Zhang and colleagues, supported by the nonprofit organization Institute for the Advancement of Food and Nutrition Sciences. The study was published recently in Nutrients.

“Nonnutritive sweeteners have no acute metabolic or endocrine effects and they are similar to water in that respect, and they show a different response from caloric sweeteners,” study author Tauseef Khan, MBBS, PhD, summarized in an interview following a press briefing from the IAFNS.

“Our study supports that nonnutritive sweeteners are a healthier alternative to sugar-sweetened beverages or caloric beverages,” said Dr. Khan, an epidemiologist in the department of nutritional sciences, University of Toronto.

Most participants in the 36 trials included in the meta-analysis were healthy, he noted. However, for certain types of NNS beverages, “we had enough studies for type 2 diabetes to also assess that separately, and the results were the same: Nonnutritive sweeteners were no different from water; however, they were different from caloric sweeteners.”

Of note, none of the studies included erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener in keto and other types of foods – which was associated with a risk for adverse cardiac events in a paper in Nature Medicine.
 

Are these NNS drinks largely inert?

“This [meta-analysis] implies that sweeteners are largely inert,” in terms of acute postprandial glucose and hormone response, but the review did not include newer reports that differ, Duane Mellor, PhD, RD, RNutr, who was not involved with the research, noted in an email.

“This is possibly,” he said, because the study “only reviewed the literature up until January 2022 and therefore it missed the World Health Organization review ‘Health Effects of the Use of Non-Sugar Sweeteners’ published in April [2022], and a study published in August 2022 in the journal Cell suggesting that some nonnutritive sweeteners may have a minor effect on gut microbiome and glucose response.

“Although there is a place of nonnutritive sweeteners as a way to reduce sugar intake, they are a small part of dietary pattern and lifestyle which can help reduce risk of disease,” said Dr. Mellor, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England.

“So, although we are clear we need to reduce our intake of sugar-sweetened beverages, switching to non-nutritive sweetened beverages (such as diet sodas) is not necessarily the healthiest option, as unlike water, it seems that some nonnutritive sweeteners may influence glucose responses and levels of related hormones in more recent studies.”
 

NNS beverages ‘are similar to water’

Dr. Khan pointed out that the meta-analysis addressed two major concerns about NNS beverages.

First, the “sweet uncoupling hypothesis” proposes that low-calorie sweeteners affect sweet taste by separating sweet taste from calories. “The body is confused, and then there is hormonal change. Our study shows that actually that’s not true, and [NNS beverages] are similar to water.”

Second, when no-calorie or low-calorie sweeteners are taken with calories (coupling), a concern is that “then you eat more somehow, or your response is different. However, the results [in this meta-analysis] also show that that is not the case for glucose response, insulin response, and other hormonal markers.”

“The strength is not that low-calorie sweeteners have some benefit per se,” he elaborated. “The advantage is that they replace caloric beverages.

“We are not saying that anybody who is not taking low-calorie sweeteners should start taking [them],” he continued. “What we are saying is somebody who is taking sugar-sweetened beverages and has a problem of taking excess calories, if you replace those calories with low-calorie sweetener, replacement of calories itself may be beneficial, and also they should not be concerned of any [acute] issues with a moderate amount of low-calorie sweeteners.”
 

Postprandial effect of NNS beverages, SSBs, water

Eight NNS are currently approved by the Food and Drug Administration: aspartame, acesulfame potassium (ace-K), luo han guo (monkfruit) extract, neotame, saccharin, stevia, sucralose, and advantame, the researchers noted.

Ms. Zhang and colleagues searched the literature up until Jan. 15, 2022, for studies of NNS beverages and acute postprandial glycemic and endocrine responses.

Trials were excluded if they involved sugar alcohols (eg, erythritol) or rare sugars (eg, allulose), or if they were shorter than 2 hours, lacked a comparator arm, or did not provide suitable endpoint data.

They identified 36 randomized and nonrandomized clinical trials of 472 predominantly healthy participants: 21 trials (15 reports, n = 266) with NNS consumed alone (uncoupled), 3 trials (3 reports, n = 27) with NNS consumed in a solution containing a carbohydrate (coupled), and 12 trials (7 reports, n = 179) with NNS consumed up to 15 minutes before oral glucose carbohydrate load (delayed coupling).

The four types of beverages were single NNS (ace-K, aspartame, cyclamate, saccharin, stevia, and sucralose), NNS blends (ace-K + aspartame; ace-K + sucralose; ace-K + aspartame + cyclamate; and ace-K + aspartame + sucralose), SSBs (glucose, sucrose, and fructose), and water (control).

In the uncoupled interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon, with responses similar to water.

In the uncoupled interventions, SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses, with no differences in postprandial ghrelin and glucagon responses.

In the coupled and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects, with responses similar to water.

The studies generally had low to moderate confidence.

The study was supported by an unrestricted grant from IAFNS. Dr. Khan has received research support from the Canadian Institutes of Health Research, the International Life Sciences Institute, and the National Honey Board. He has received honorariums for lectures from the International Food Information Council and the IAFNS. Dr. Mellor has no disclosures.

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

Drinking a no-or low-calorie nonnutritive sweetened (NNS) beverage was no different from drinking water in terms of effect on 2-hour postprandial levels of glucose and hormones related to appetite or food intake.

Drinking a sugar-sweetened beverage (SSB), however, had a different effect on postprandial levels of glucose and the hormones insulin, glucagonlike peptide–1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon.

These findings are from a new meta-analysis by Roselyn Zhang and colleagues, supported by the nonprofit organization Institute for the Advancement of Food and Nutrition Sciences. The study was published recently in Nutrients.

“Nonnutritive sweeteners have no acute metabolic or endocrine effects and they are similar to water in that respect, and they show a different response from caloric sweeteners,” study author Tauseef Khan, MBBS, PhD, summarized in an interview following a press briefing from the IAFNS.

“Our study supports that nonnutritive sweeteners are a healthier alternative to sugar-sweetened beverages or caloric beverages,” said Dr. Khan, an epidemiologist in the department of nutritional sciences, University of Toronto.

Most participants in the 36 trials included in the meta-analysis were healthy, he noted. However, for certain types of NNS beverages, “we had enough studies for type 2 diabetes to also assess that separately, and the results were the same: Nonnutritive sweeteners were no different from water; however, they were different from caloric sweeteners.”

Of note, none of the studies included erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener in keto and other types of foods – which was associated with a risk for adverse cardiac events in a paper in Nature Medicine.
 

Are these NNS drinks largely inert?

“This [meta-analysis] implies that sweeteners are largely inert,” in terms of acute postprandial glucose and hormone response, but the review did not include newer reports that differ, Duane Mellor, PhD, RD, RNutr, who was not involved with the research, noted in an email.

“This is possibly,” he said, because the study “only reviewed the literature up until January 2022 and therefore it missed the World Health Organization review ‘Health Effects of the Use of Non-Sugar Sweeteners’ published in April [2022], and a study published in August 2022 in the journal Cell suggesting that some nonnutritive sweeteners may have a minor effect on gut microbiome and glucose response.

“Although there is a place of nonnutritive sweeteners as a way to reduce sugar intake, they are a small part of dietary pattern and lifestyle which can help reduce risk of disease,” said Dr. Mellor, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England.

“So, although we are clear we need to reduce our intake of sugar-sweetened beverages, switching to non-nutritive sweetened beverages (such as diet sodas) is not necessarily the healthiest option, as unlike water, it seems that some nonnutritive sweeteners may influence glucose responses and levels of related hormones in more recent studies.”
 

NNS beverages ‘are similar to water’

Dr. Khan pointed out that the meta-analysis addressed two major concerns about NNS beverages.

First, the “sweet uncoupling hypothesis” proposes that low-calorie sweeteners affect sweet taste by separating sweet taste from calories. “The body is confused, and then there is hormonal change. Our study shows that actually that’s not true, and [NNS beverages] are similar to water.”

Second, when no-calorie or low-calorie sweeteners are taken with calories (coupling), a concern is that “then you eat more somehow, or your response is different. However, the results [in this meta-analysis] also show that that is not the case for glucose response, insulin response, and other hormonal markers.”

“The strength is not that low-calorie sweeteners have some benefit per se,” he elaborated. “The advantage is that they replace caloric beverages.

“We are not saying that anybody who is not taking low-calorie sweeteners should start taking [them],” he continued. “What we are saying is somebody who is taking sugar-sweetened beverages and has a problem of taking excess calories, if you replace those calories with low-calorie sweetener, replacement of calories itself may be beneficial, and also they should not be concerned of any [acute] issues with a moderate amount of low-calorie sweeteners.”
 

Postprandial effect of NNS beverages, SSBs, water

Eight NNS are currently approved by the Food and Drug Administration: aspartame, acesulfame potassium (ace-K), luo han guo (monkfruit) extract, neotame, saccharin, stevia, sucralose, and advantame, the researchers noted.

Ms. Zhang and colleagues searched the literature up until Jan. 15, 2022, for studies of NNS beverages and acute postprandial glycemic and endocrine responses.

Trials were excluded if they involved sugar alcohols (eg, erythritol) or rare sugars (eg, allulose), or if they were shorter than 2 hours, lacked a comparator arm, or did not provide suitable endpoint data.

They identified 36 randomized and nonrandomized clinical trials of 472 predominantly healthy participants: 21 trials (15 reports, n = 266) with NNS consumed alone (uncoupled), 3 trials (3 reports, n = 27) with NNS consumed in a solution containing a carbohydrate (coupled), and 12 trials (7 reports, n = 179) with NNS consumed up to 15 minutes before oral glucose carbohydrate load (delayed coupling).

The four types of beverages were single NNS (ace-K, aspartame, cyclamate, saccharin, stevia, and sucralose), NNS blends (ace-K + aspartame; ace-K + sucralose; ace-K + aspartame + cyclamate; and ace-K + aspartame + sucralose), SSBs (glucose, sucrose, and fructose), and water (control).

In the uncoupled interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon, with responses similar to water.

In the uncoupled interventions, SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses, with no differences in postprandial ghrelin and glucagon responses.

In the coupled and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects, with responses similar to water.

The studies generally had low to moderate confidence.

The study was supported by an unrestricted grant from IAFNS. Dr. Khan has received research support from the Canadian Institutes of Health Research, the International Life Sciences Institute, and the National Honey Board. He has received honorariums for lectures from the International Food Information Council and the IAFNS. Dr. Mellor has no disclosures.

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

Drinking a no-or low-calorie nonnutritive sweetened (NNS) beverage was no different from drinking water in terms of effect on 2-hour postprandial levels of glucose and hormones related to appetite or food intake.

Drinking a sugar-sweetened beverage (SSB), however, had a different effect on postprandial levels of glucose and the hormones insulin, glucagonlike peptide–1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon.

These findings are from a new meta-analysis by Roselyn Zhang and colleagues, supported by the nonprofit organization Institute for the Advancement of Food and Nutrition Sciences. The study was published recently in Nutrients.

“Nonnutritive sweeteners have no acute metabolic or endocrine effects and they are similar to water in that respect, and they show a different response from caloric sweeteners,” study author Tauseef Khan, MBBS, PhD, summarized in an interview following a press briefing from the IAFNS.

“Our study supports that nonnutritive sweeteners are a healthier alternative to sugar-sweetened beverages or caloric beverages,” said Dr. Khan, an epidemiologist in the department of nutritional sciences, University of Toronto.

Most participants in the 36 trials included in the meta-analysis were healthy, he noted. However, for certain types of NNS beverages, “we had enough studies for type 2 diabetes to also assess that separately, and the results were the same: Nonnutritive sweeteners were no different from water; however, they were different from caloric sweeteners.”

Of note, none of the studies included erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener in keto and other types of foods – which was associated with a risk for adverse cardiac events in a paper in Nature Medicine.
 

Are these NNS drinks largely inert?

“This [meta-analysis] implies that sweeteners are largely inert,” in terms of acute postprandial glucose and hormone response, but the review did not include newer reports that differ, Duane Mellor, PhD, RD, RNutr, who was not involved with the research, noted in an email.

“This is possibly,” he said, because the study “only reviewed the literature up until January 2022 and therefore it missed the World Health Organization review ‘Health Effects of the Use of Non-Sugar Sweeteners’ published in April [2022], and a study published in August 2022 in the journal Cell suggesting that some nonnutritive sweeteners may have a minor effect on gut microbiome and glucose response.

“Although there is a place of nonnutritive sweeteners as a way to reduce sugar intake, they are a small part of dietary pattern and lifestyle which can help reduce risk of disease,” said Dr. Mellor, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England.

“So, although we are clear we need to reduce our intake of sugar-sweetened beverages, switching to non-nutritive sweetened beverages (such as diet sodas) is not necessarily the healthiest option, as unlike water, it seems that some nonnutritive sweeteners may influence glucose responses and levels of related hormones in more recent studies.”
 

NNS beverages ‘are similar to water’

Dr. Khan pointed out that the meta-analysis addressed two major concerns about NNS beverages.

First, the “sweet uncoupling hypothesis” proposes that low-calorie sweeteners affect sweet taste by separating sweet taste from calories. “The body is confused, and then there is hormonal change. Our study shows that actually that’s not true, and [NNS beverages] are similar to water.”

Second, when no-calorie or low-calorie sweeteners are taken with calories (coupling), a concern is that “then you eat more somehow, or your response is different. However, the results [in this meta-analysis] also show that that is not the case for glucose response, insulin response, and other hormonal markers.”

“The strength is not that low-calorie sweeteners have some benefit per se,” he elaborated. “The advantage is that they replace caloric beverages.

“We are not saying that anybody who is not taking low-calorie sweeteners should start taking [them],” he continued. “What we are saying is somebody who is taking sugar-sweetened beverages and has a problem of taking excess calories, if you replace those calories with low-calorie sweetener, replacement of calories itself may be beneficial, and also they should not be concerned of any [acute] issues with a moderate amount of low-calorie sweeteners.”
 

Postprandial effect of NNS beverages, SSBs, water

Eight NNS are currently approved by the Food and Drug Administration: aspartame, acesulfame potassium (ace-K), luo han guo (monkfruit) extract, neotame, saccharin, stevia, sucralose, and advantame, the researchers noted.

Ms. Zhang and colleagues searched the literature up until Jan. 15, 2022, for studies of NNS beverages and acute postprandial glycemic and endocrine responses.

Trials were excluded if they involved sugar alcohols (eg, erythritol) or rare sugars (eg, allulose), or if they were shorter than 2 hours, lacked a comparator arm, or did not provide suitable endpoint data.

They identified 36 randomized and nonrandomized clinical trials of 472 predominantly healthy participants: 21 trials (15 reports, n = 266) with NNS consumed alone (uncoupled), 3 trials (3 reports, n = 27) with NNS consumed in a solution containing a carbohydrate (coupled), and 12 trials (7 reports, n = 179) with NNS consumed up to 15 minutes before oral glucose carbohydrate load (delayed coupling).

The four types of beverages were single NNS (ace-K, aspartame, cyclamate, saccharin, stevia, and sucralose), NNS blends (ace-K + aspartame; ace-K + sucralose; ace-K + aspartame + cyclamate; and ace-K + aspartame + sucralose), SSBs (glucose, sucrose, and fructose), and water (control).

In the uncoupled interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon, with responses similar to water.

In the uncoupled interventions, SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses, with no differences in postprandial ghrelin and glucagon responses.

In the coupled and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects, with responses similar to water.

The studies generally had low to moderate confidence.

The study was supported by an unrestricted grant from IAFNS. Dr. Khan has received research support from the Canadian Institutes of Health Research, the International Life Sciences Institute, and the National Honey Board. He has received honorariums for lectures from the International Food Information Council and the IAFNS. Dr. Mellor has no disclosures.

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

New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.

In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.

Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.

Preventing a tsunami of heart disease

The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.

Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.

Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).

Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.

The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).

“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.

NYU Langone

Double down on screening

Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”

“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.

Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”

As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”

“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.

“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.

In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”

The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.

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

New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.

In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.

Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.

Preventing a tsunami of heart disease

The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.

Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.

Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).

Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.

The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).

“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.

NYU Langone

Double down on screening

Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”

“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.

Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”

As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”

“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.

“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.

In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”

The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.

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

New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.

In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.

Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.

Preventing a tsunami of heart disease

The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.

Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.

Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).

Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.

The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).

“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.

NYU Langone

Double down on screening

Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”

“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.

Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”

As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”

“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.

“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.

In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”

The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.

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

If budesonide-formoterol were to become available over the counter (OTC) and used as-needed for mild asthma, it would save lives and cut health care costs, according to a computer modeling study presented at the American Academy of Allergy, Asthma, and Immunology 2023 annual meeting in San Antonio.

Asthma affects 25 million people, about 1 in 13, in the United States. About 28% are uninsured or underinsured, and 70% have mild asthma. Many are using a $30 inhaled epinephrine product (Primatene Mist) – the only FDA-approved asthma inhaler available without a prescription, said Marcus Shaker, MD, MS, professor of pediatrics and medicine at Geisel School of Medicine at Dartmouth, and clinician at Dartmouth Health Children’s, N.H.

A new version of Primatene Mist was reintroduced on the market in 2018 after the product was pulled for containing chlorofluorocarbons in 2011, but it is not recommended by professional medical societies because of safety concerns over epinephrine’s adverse effects, such as increased heart rate and blood pressure.

Drugs in its class (bronchodilators) have long been associated with a higher risk for death or near-death.

Meanwhile, research more than 2 decades ago linked regular use of low-dose inhaled corticosteroids with reduced risk for asthma death.

More recently, two large studies (SYGMA 1 and SYGMA 2) compared maintenance therapy with a low-dose inhaled corticosteroid (budesonide) vs. on-demand treatment with an inhaler containing both a corticosteroid (budesonide) and a long-acting bronchodilator (formoterol).

“Using as-needed budesonide-formoterol led to outcomes that are almost as good as taking a maintenance budesonide dose every day,” said Dr. Shaker.

The Global Initiative for Asthma guidelines now recommend this approach – as-needed inhaled corticosteroids (ICS) plus long-acting bronchodilators – for adults with mild asthma. In the United States, however, the National Heart, Lung, and Blood Institute still suggests daily ICS plus quick-relief therapy as needed.

Dr. Shaker and colleagues used computer modeling to compare the cost-effectiveness of as-needed budesonide-formoterol vs. over-the-counter inhaled epinephrine in underinsured U.S. adults who were self-managing their mild asthma. The study randomly assigned these individuals into three groups: OTC inhaled epinephrine (current reality), OTC budesonide-formoterol (not yet available), or no OTC option. The model assumed that patients treated for an exacerbation were referred to a health care provider and started a regimen of ICS plus as-needed rescue therapy.

In this analysis, which has been submitted for publication, the OTC budesonide-formoterol strategy was associated with 12,495 fewer deaths, prevented nearly 14 million severe asthma exacerbations, and saved more than $68 billion. And “when we looked at OTC budesonide-formoterol vs. having no OTC option at all, budesonide-formoterol was similarly cost-effective,” said Dr. Shaker, who presented the results at an AAAAI oral abstract session.

The cost savings emerged even though in the United States asthma controller therapies (for example, fluticasone) cost about 10 times more than rescue therapies (for instance, salbutamol, OTC epinephrine).

Nevertheless, the results make sense. “If you’re using Primatene Mist, your health costs are predicted to be much greater because you’re going to be in the hospital more. Your asthma is not going to be well-controlled,” Thanai Pongdee, MD, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., told this news organization. “It’s not only the cost of your ER visit but also the cost of loss of work or school, and loss of daily productivity. There are all these associated costs.”

The analysis “is certainly something policy makers could take a look at,” he said.

He noted that current use of budesonide-formoterol is stymied by difficulties with insurance coverage. The difficulties stem from a mismatch between the updated recommendation for as-needed use and the description printed on the brand-name product (Symbicort).

“On the product label, it says Symbicort should be used on a daily basis,” Dr. Pongdee said. “But if a prescription comes through and says you’re going to use this ‘as needed,’ the health plan may say that’s not appropriate because that’s not on the product label.”

Given these access challenges with the all-in-one inhaler, other researchers have developed a workaround – asking patients to continue their usual care (that is, using a rescue inhaler as needed) but to also administer a controller medication after each rescue. When tested in Black and Latino patients with moderate to severe asthma, this easy strategy (patient activated reliever-triggered inhaled corticosteroid, or PARTICS) reduced severe asthma exacerbations about as well as the all-in-one inhaler.

If the all-in-one budesonide-formoterol does become available OTC, Dr. Shaker stressed that it “would not be a substitute for seeing an allergist and getting appropriate medical care and an evaluation and all the rest. But it’s better than the status quo. It’s the sort of thing where the perfect is not the enemy of the good,” he said.

Dr. Shaker is the AAAAI cochair of the Joint Task Force on Practice Parameters and serves as an editorial board member of the Journal of Allergy and Clinical Immunology in Practice. He is also an associate editor of the Annals of Allergy, Asthma, and Immunology. Dr. Pongdee serves as an at-large director on the AAAAI board of directors. He receives grant funding from GlaxoSmithKline, and Mayo Clinic is a trial site for GlaxoSmithKline and AstraZeneca.

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

If budesonide-formoterol were to become available over the counter (OTC) and used as-needed for mild asthma, it would save lives and cut health care costs, according to a computer modeling study presented at the American Academy of Allergy, Asthma, and Immunology 2023 annual meeting in San Antonio.

Asthma affects 25 million people, about 1 in 13, in the United States. About 28% are uninsured or underinsured, and 70% have mild asthma. Many are using a $30 inhaled epinephrine product (Primatene Mist) – the only FDA-approved asthma inhaler available without a prescription, said Marcus Shaker, MD, MS, professor of pediatrics and medicine at Geisel School of Medicine at Dartmouth, and clinician at Dartmouth Health Children’s, N.H.

A new version of Primatene Mist was reintroduced on the market in 2018 after the product was pulled for containing chlorofluorocarbons in 2011, but it is not recommended by professional medical societies because of safety concerns over epinephrine’s adverse effects, such as increased heart rate and blood pressure.

Drugs in its class (bronchodilators) have long been associated with a higher risk for death or near-death.

Meanwhile, research more than 2 decades ago linked regular use of low-dose inhaled corticosteroids with reduced risk for asthma death.

More recently, two large studies (SYGMA 1 and SYGMA 2) compared maintenance therapy with a low-dose inhaled corticosteroid (budesonide) vs. on-demand treatment with an inhaler containing both a corticosteroid (budesonide) and a long-acting bronchodilator (formoterol).

“Using as-needed budesonide-formoterol led to outcomes that are almost as good as taking a maintenance budesonide dose every day,” said Dr. Shaker.

The Global Initiative for Asthma guidelines now recommend this approach – as-needed inhaled corticosteroids (ICS) plus long-acting bronchodilators – for adults with mild asthma. In the United States, however, the National Heart, Lung, and Blood Institute still suggests daily ICS plus quick-relief therapy as needed.

Dr. Shaker and colleagues used computer modeling to compare the cost-effectiveness of as-needed budesonide-formoterol vs. over-the-counter inhaled epinephrine in underinsured U.S. adults who were self-managing their mild asthma. The study randomly assigned these individuals into three groups: OTC inhaled epinephrine (current reality), OTC budesonide-formoterol (not yet available), or no OTC option. The model assumed that patients treated for an exacerbation were referred to a health care provider and started a regimen of ICS plus as-needed rescue therapy.

In this analysis, which has been submitted for publication, the OTC budesonide-formoterol strategy was associated with 12,495 fewer deaths, prevented nearly 14 million severe asthma exacerbations, and saved more than $68 billion. And “when we looked at OTC budesonide-formoterol vs. having no OTC option at all, budesonide-formoterol was similarly cost-effective,” said Dr. Shaker, who presented the results at an AAAAI oral abstract session.

The cost savings emerged even though in the United States asthma controller therapies (for example, fluticasone) cost about 10 times more than rescue therapies (for instance, salbutamol, OTC epinephrine).

Nevertheless, the results make sense. “If you’re using Primatene Mist, your health costs are predicted to be much greater because you’re going to be in the hospital more. Your asthma is not going to be well-controlled,” Thanai Pongdee, MD, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., told this news organization. “It’s not only the cost of your ER visit but also the cost of loss of work or school, and loss of daily productivity. There are all these associated costs.”

The analysis “is certainly something policy makers could take a look at,” he said.

He noted that current use of budesonide-formoterol is stymied by difficulties with insurance coverage. The difficulties stem from a mismatch between the updated recommendation for as-needed use and the description printed on the brand-name product (Symbicort).

“On the product label, it says Symbicort should be used on a daily basis,” Dr. Pongdee said. “But if a prescription comes through and says you’re going to use this ‘as needed,’ the health plan may say that’s not appropriate because that’s not on the product label.”

Given these access challenges with the all-in-one inhaler, other researchers have developed a workaround – asking patients to continue their usual care (that is, using a rescue inhaler as needed) but to also administer a controller medication after each rescue. When tested in Black and Latino patients with moderate to severe asthma, this easy strategy (patient activated reliever-triggered inhaled corticosteroid, or PARTICS) reduced severe asthma exacerbations about as well as the all-in-one inhaler.

If the all-in-one budesonide-formoterol does become available OTC, Dr. Shaker stressed that it “would not be a substitute for seeing an allergist and getting appropriate medical care and an evaluation and all the rest. But it’s better than the status quo. It’s the sort of thing where the perfect is not the enemy of the good,” he said.

Dr. Shaker is the AAAAI cochair of the Joint Task Force on Practice Parameters and serves as an editorial board member of the Journal of Allergy and Clinical Immunology in Practice. He is also an associate editor of the Annals of Allergy, Asthma, and Immunology. Dr. Pongdee serves as an at-large director on the AAAAI board of directors. He receives grant funding from GlaxoSmithKline, and Mayo Clinic is a trial site for GlaxoSmithKline and AstraZeneca.

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

If budesonide-formoterol were to become available over the counter (OTC) and used as-needed for mild asthma, it would save lives and cut health care costs, according to a computer modeling study presented at the American Academy of Allergy, Asthma, and Immunology 2023 annual meeting in San Antonio.

Asthma affects 25 million people, about 1 in 13, in the United States. About 28% are uninsured or underinsured, and 70% have mild asthma. Many are using a $30 inhaled epinephrine product (Primatene Mist) – the only FDA-approved asthma inhaler available without a prescription, said Marcus Shaker, MD, MS, professor of pediatrics and medicine at Geisel School of Medicine at Dartmouth, and clinician at Dartmouth Health Children’s, N.H.

A new version of Primatene Mist was reintroduced on the market in 2018 after the product was pulled for containing chlorofluorocarbons in 2011, but it is not recommended by professional medical societies because of safety concerns over epinephrine’s adverse effects, such as increased heart rate and blood pressure.

Drugs in its class (bronchodilators) have long been associated with a higher risk for death or near-death.

Meanwhile, research more than 2 decades ago linked regular use of low-dose inhaled corticosteroids with reduced risk for asthma death.

More recently, two large studies (SYGMA 1 and SYGMA 2) compared maintenance therapy with a low-dose inhaled corticosteroid (budesonide) vs. on-demand treatment with an inhaler containing both a corticosteroid (budesonide) and a long-acting bronchodilator (formoterol).

“Using as-needed budesonide-formoterol led to outcomes that are almost as good as taking a maintenance budesonide dose every day,” said Dr. Shaker.

The Global Initiative for Asthma guidelines now recommend this approach – as-needed inhaled corticosteroids (ICS) plus long-acting bronchodilators – for adults with mild asthma. In the United States, however, the National Heart, Lung, and Blood Institute still suggests daily ICS plus quick-relief therapy as needed.

Dr. Shaker and colleagues used computer modeling to compare the cost-effectiveness of as-needed budesonide-formoterol vs. over-the-counter inhaled epinephrine in underinsured U.S. adults who were self-managing their mild asthma. The study randomly assigned these individuals into three groups: OTC inhaled epinephrine (current reality), OTC budesonide-formoterol (not yet available), or no OTC option. The model assumed that patients treated for an exacerbation were referred to a health care provider and started a regimen of ICS plus as-needed rescue therapy.

In this analysis, which has been submitted for publication, the OTC budesonide-formoterol strategy was associated with 12,495 fewer deaths, prevented nearly 14 million severe asthma exacerbations, and saved more than $68 billion. And “when we looked at OTC budesonide-formoterol vs. having no OTC option at all, budesonide-formoterol was similarly cost-effective,” said Dr. Shaker, who presented the results at an AAAAI oral abstract session.

The cost savings emerged even though in the United States asthma controller therapies (for example, fluticasone) cost about 10 times more than rescue therapies (for instance, salbutamol, OTC epinephrine).

Nevertheless, the results make sense. “If you’re using Primatene Mist, your health costs are predicted to be much greater because you’re going to be in the hospital more. Your asthma is not going to be well-controlled,” Thanai Pongdee, MD, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., told this news organization. “It’s not only the cost of your ER visit but also the cost of loss of work or school, and loss of daily productivity. There are all these associated costs.”

The analysis “is certainly something policy makers could take a look at,” he said.

He noted that current use of budesonide-formoterol is stymied by difficulties with insurance coverage. The difficulties stem from a mismatch between the updated recommendation for as-needed use and the description printed on the brand-name product (Symbicort).

“On the product label, it says Symbicort should be used on a daily basis,” Dr. Pongdee said. “But if a prescription comes through and says you’re going to use this ‘as needed,’ the health plan may say that’s not appropriate because that’s not on the product label.”

Given these access challenges with the all-in-one inhaler, other researchers have developed a workaround – asking patients to continue their usual care (that is, using a rescue inhaler as needed) but to also administer a controller medication after each rescue. When tested in Black and Latino patients with moderate to severe asthma, this easy strategy (patient activated reliever-triggered inhaled corticosteroid, or PARTICS) reduced severe asthma exacerbations about as well as the all-in-one inhaler.

If the all-in-one budesonide-formoterol does become available OTC, Dr. Shaker stressed that it “would not be a substitute for seeing an allergist and getting appropriate medical care and an evaluation and all the rest. But it’s better than the status quo. It’s the sort of thing where the perfect is not the enemy of the good,” he said.

Dr. Shaker is the AAAAI cochair of the Joint Task Force on Practice Parameters and serves as an editorial board member of the Journal of Allergy and Clinical Immunology in Practice. He is also an associate editor of the Annals of Allergy, Asthma, and Immunology. Dr. Pongdee serves as an at-large director on the AAAAI board of directors. He receives grant funding from GlaxoSmithKline, and Mayo Clinic is a trial site for GlaxoSmithKline and AstraZeneca.

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

I am often asked about the impact of dietary nutrients on bone health, particularly as many patients with low bone density, many with a history of multiple fractures, are referred to me. Many factors affect bone density, an important predictor of fracture risk, including genetics, body weight and muscle mass, bone loading exercise, menstrual status, other hormonal factors, nutritional status, optimal absorption of dietary nutrients, and medication use.

Dietary nutrients include macronutrients (carbohydrates, proteins, fat, and fiber) and micronutrients (such as dietary minerals and vitamins). The importance of micronutrients such as calcium, phosphorus, magnesium, and vitamins C, D, and K in optimizing bone mineralization and bone formation has been well documented.

The impact of protein intake on bone health is slightly more controversial, with some studies suggesting that increased protein intake may be deleterious to bone by increasing acid load, which in turn, increases calcium loss in urine. Overall data analysis from multiple studies support the finding that a higher protein intake is modestly beneficial for bone at certain sites, such as the spine.

Though data regarding the impact of dietary carbohydrates on bone are not as robust, it’s important to understand these effects given the increasing knowledge of the deleterious impact of processed carbohydrates on weight and cardiometabolic outcomes. This leads to the growing recommendations to limit carbohydrates in diet.
 

Quality and quantity of carbs affect bone health

Available studies suggest that both the quality and quantity of carbohydrates that are in a diet as well as the glycemic index of food may affect bone outcomes. Glycemic index refers to the extent of blood glucose elevation that occurs after the intake of any specific food. Foods with a higher glycemic index cause a rapid increase in blood glucose, whereas those with a low glycemic index result in a slower and more gradual increase. Examples of high–glycemic index food include processed and baked foods (such as breakfast cereals [unless whole grain], pretzels, cookies, doughnuts, pastries, cake, white bread, bagels, croissants, and corn chips), sugar-sweetened beverages, white rice, fast food (such as pizza and burgers), and potatoes. Examples of low glycemic index foods include vegetables, fruits, legumes, dairy and dairy products (without added sugar), whole-grain foods (such as oat porridge), and nuts.

A high–glycemic index diet has been associated with a greater risk for obesity and cardiovascular disease, and with lower bone density, an increased risk for fracture. This has been attributed to acute increases in glucose and insulin levels after consumption of high–glycemic index food, which causes increased oxidative stress and secretion of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, that activate cells in bone that increase bone loss.

Higher blood glucose concentrations induced by a higher dietary glycemic index can have deleterious effects on osteoblasts, the cells important for bone formation, and increase bone loss through production of advanced glycation end products that affect the cross linking of collagen in bone (important for bone strength), as well as calcium loss in urine. This was recently reported in a study by Garcia-Gavilan and others, in which the authors showed that high dietary glycemic index and dietary glucose load are associated with a higher risk for osteoporosis-related fractures in an older Mediterranean population who are at high risk for cardiovascular events. Similar data were reported by Nouri and coauthors in a study from Iran.

The quantity and quality of dietary carbohydrates may also have an impact on bone. The quality of carbohydrates has been assessed using the carbohydrate quality index (CQI) and the low carbohydrate diet score (LCDS). The CQI takes into account dietary fiber intake, glycemic index, intake of processed vs. whole grain, and solid vs. total carbohydrates in diet. A higher CQI diet is associated with reduced cardiovascular risk. Higher LCDS reflects lower carbohydrate and higher fat and protein intake.

Diets that are rich in refined or processed carbohydrates with added sugar are proinflammatory and increase oxidative stress, which may lead to increased bone loss, low bone density, and increased fracture risk. These foods also have a high glycemic index.

In contrast, diets that are rich in whole grains, legumes, fruits, vegetables, nuts, and olive oil have a lower glycemic index and are beneficial to bone. These diets have a higher CQI and LCDS (as reported by Nouri and coauthors) and provide a rich source of antioxidants, vitamins, minerals, and other nutrients (such as calcium, magnesium, and vitamins B, C, and K), which are all beneficial to bone. Gao and others have reported that implementing a low glycemic index pulse-based diet (lentils, peas, beans) is superior to a regular hospital diet in preventing the increase in bone loss that typically occurs during hospitalization with enforced bed rest.

Most reports of the impact of carbohydrates on bone health are from observational studies. In an interventional study, Dalskov and coauthors randomly assigned children aged 5-18 years who had parents with overweight to one of five diets (high protein/low glycemic index, high protein/high glycemic index, low protein/low glycemic index, low protein/high glycemic index, or regular) for 6 months.

Contrasting with our understanding that protein intake is overall good for bone, this study found that among patients receiving a high–glycemic index diet, those who were on a high-protein diet had greater reductions in a bone formation marker than did those on a low-protein diet, with no major changes observed with the other diets. This suggests the influence of associated dietary nutrients on bone outcomes and that protein intake may modify the effects of dietary carbohydrates on bone formation. Similarly, the fat content of food can alter the glycemic index and thus may modify the impact of dietary carbohydrates on bone.

In summary, available data suggest that the quantity and quality of carbohydrates, including the glycemic index of food, may affect bone health and that it is important to exercise moderation in the consumption of such foods. However, there are only a few studies that have examined these associations, and more studies are necessary to further clarify the impact of dietary carbohydrates on bone as well as any modifications of these effects by other associated food groups. These studies will allow us to refine our recommendations to our patients as we advance our understanding of the impact of the combined effects of various dietary nutrients on bone.

Madhusmita Misra, MD, MPH, is chief of the division of pediatric endocrinology, Mass General for Children, Boston, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for AbbVie, Sanofi, and Ipsen.

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

I am often asked about the impact of dietary nutrients on bone health, particularly as many patients with low bone density, many with a history of multiple fractures, are referred to me. Many factors affect bone density, an important predictor of fracture risk, including genetics, body weight and muscle mass, bone loading exercise, menstrual status, other hormonal factors, nutritional status, optimal absorption of dietary nutrients, and medication use.

Dietary nutrients include macronutrients (carbohydrates, proteins, fat, and fiber) and micronutrients (such as dietary minerals and vitamins). The importance of micronutrients such as calcium, phosphorus, magnesium, and vitamins C, D, and K in optimizing bone mineralization and bone formation has been well documented.

The impact of protein intake on bone health is slightly more controversial, with some studies suggesting that increased protein intake may be deleterious to bone by increasing acid load, which in turn, increases calcium loss in urine. Overall data analysis from multiple studies support the finding that a higher protein intake is modestly beneficial for bone at certain sites, such as the spine.

Though data regarding the impact of dietary carbohydrates on bone are not as robust, it’s important to understand these effects given the increasing knowledge of the deleterious impact of processed carbohydrates on weight and cardiometabolic outcomes. This leads to the growing recommendations to limit carbohydrates in diet.
 

Quality and quantity of carbs affect bone health

Available studies suggest that both the quality and quantity of carbohydrates that are in a diet as well as the glycemic index of food may affect bone outcomes. Glycemic index refers to the extent of blood glucose elevation that occurs after the intake of any specific food. Foods with a higher glycemic index cause a rapid increase in blood glucose, whereas those with a low glycemic index result in a slower and more gradual increase. Examples of high–glycemic index food include processed and baked foods (such as breakfast cereals [unless whole grain], pretzels, cookies, doughnuts, pastries, cake, white bread, bagels, croissants, and corn chips), sugar-sweetened beverages, white rice, fast food (such as pizza and burgers), and potatoes. Examples of low glycemic index foods include vegetables, fruits, legumes, dairy and dairy products (without added sugar), whole-grain foods (such as oat porridge), and nuts.

A high–glycemic index diet has been associated with a greater risk for obesity and cardiovascular disease, and with lower bone density, an increased risk for fracture. This has been attributed to acute increases in glucose and insulin levels after consumption of high–glycemic index food, which causes increased oxidative stress and secretion of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, that activate cells in bone that increase bone loss.

Higher blood glucose concentrations induced by a higher dietary glycemic index can have deleterious effects on osteoblasts, the cells important for bone formation, and increase bone loss through production of advanced glycation end products that affect the cross linking of collagen in bone (important for bone strength), as well as calcium loss in urine. This was recently reported in a study by Garcia-Gavilan and others, in which the authors showed that high dietary glycemic index and dietary glucose load are associated with a higher risk for osteoporosis-related fractures in an older Mediterranean population who are at high risk for cardiovascular events. Similar data were reported by Nouri and coauthors in a study from Iran.

The quantity and quality of dietary carbohydrates may also have an impact on bone. The quality of carbohydrates has been assessed using the carbohydrate quality index (CQI) and the low carbohydrate diet score (LCDS). The CQI takes into account dietary fiber intake, glycemic index, intake of processed vs. whole grain, and solid vs. total carbohydrates in diet. A higher CQI diet is associated with reduced cardiovascular risk. Higher LCDS reflects lower carbohydrate and higher fat and protein intake.

Diets that are rich in refined or processed carbohydrates with added sugar are proinflammatory and increase oxidative stress, which may lead to increased bone loss, low bone density, and increased fracture risk. These foods also have a high glycemic index.

In contrast, diets that are rich in whole grains, legumes, fruits, vegetables, nuts, and olive oil have a lower glycemic index and are beneficial to bone. These diets have a higher CQI and LCDS (as reported by Nouri and coauthors) and provide a rich source of antioxidants, vitamins, minerals, and other nutrients (such as calcium, magnesium, and vitamins B, C, and K), which are all beneficial to bone. Gao and others have reported that implementing a low glycemic index pulse-based diet (lentils, peas, beans) is superior to a regular hospital diet in preventing the increase in bone loss that typically occurs during hospitalization with enforced bed rest.

Most reports of the impact of carbohydrates on bone health are from observational studies. In an interventional study, Dalskov and coauthors randomly assigned children aged 5-18 years who had parents with overweight to one of five diets (high protein/low glycemic index, high protein/high glycemic index, low protein/low glycemic index, low protein/high glycemic index, or regular) for 6 months.

Contrasting with our understanding that protein intake is overall good for bone, this study found that among patients receiving a high–glycemic index diet, those who were on a high-protein diet had greater reductions in a bone formation marker than did those on a low-protein diet, with no major changes observed with the other diets. This suggests the influence of associated dietary nutrients on bone outcomes and that protein intake may modify the effects of dietary carbohydrates on bone formation. Similarly, the fat content of food can alter the glycemic index and thus may modify the impact of dietary carbohydrates on bone.

In summary, available data suggest that the quantity and quality of carbohydrates, including the glycemic index of food, may affect bone health and that it is important to exercise moderation in the consumption of such foods. However, there are only a few studies that have examined these associations, and more studies are necessary to further clarify the impact of dietary carbohydrates on bone as well as any modifications of these effects by other associated food groups. These studies will allow us to refine our recommendations to our patients as we advance our understanding of the impact of the combined effects of various dietary nutrients on bone.

Madhusmita Misra, MD, MPH, is chief of the division of pediatric endocrinology, Mass General for Children, Boston, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for AbbVie, Sanofi, and Ipsen.

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

I am often asked about the impact of dietary nutrients on bone health, particularly as many patients with low bone density, many with a history of multiple fractures, are referred to me. Many factors affect bone density, an important predictor of fracture risk, including genetics, body weight and muscle mass, bone loading exercise, menstrual status, other hormonal factors, nutritional status, optimal absorption of dietary nutrients, and medication use.

Dietary nutrients include macronutrients (carbohydrates, proteins, fat, and fiber) and micronutrients (such as dietary minerals and vitamins). The importance of micronutrients such as calcium, phosphorus, magnesium, and vitamins C, D, and K in optimizing bone mineralization and bone formation has been well documented.

The impact of protein intake on bone health is slightly more controversial, with some studies suggesting that increased protein intake may be deleterious to bone by increasing acid load, which in turn, increases calcium loss in urine. Overall data analysis from multiple studies support the finding that a higher protein intake is modestly beneficial for bone at certain sites, such as the spine.

Though data regarding the impact of dietary carbohydrates on bone are not as robust, it’s important to understand these effects given the increasing knowledge of the deleterious impact of processed carbohydrates on weight and cardiometabolic outcomes. This leads to the growing recommendations to limit carbohydrates in diet.
 

Quality and quantity of carbs affect bone health

Available studies suggest that both the quality and quantity of carbohydrates that are in a diet as well as the glycemic index of food may affect bone outcomes. Glycemic index refers to the extent of blood glucose elevation that occurs after the intake of any specific food. Foods with a higher glycemic index cause a rapid increase in blood glucose, whereas those with a low glycemic index result in a slower and more gradual increase. Examples of high–glycemic index food include processed and baked foods (such as breakfast cereals [unless whole grain], pretzels, cookies, doughnuts, pastries, cake, white bread, bagels, croissants, and corn chips), sugar-sweetened beverages, white rice, fast food (such as pizza and burgers), and potatoes. Examples of low glycemic index foods include vegetables, fruits, legumes, dairy and dairy products (without added sugar), whole-grain foods (such as oat porridge), and nuts.

A high–glycemic index diet has been associated with a greater risk for obesity and cardiovascular disease, and with lower bone density, an increased risk for fracture. This has been attributed to acute increases in glucose and insulin levels after consumption of high–glycemic index food, which causes increased oxidative stress and secretion of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, that activate cells in bone that increase bone loss.

Higher blood glucose concentrations induced by a higher dietary glycemic index can have deleterious effects on osteoblasts, the cells important for bone formation, and increase bone loss through production of advanced glycation end products that affect the cross linking of collagen in bone (important for bone strength), as well as calcium loss in urine. This was recently reported in a study by Garcia-Gavilan and others, in which the authors showed that high dietary glycemic index and dietary glucose load are associated with a higher risk for osteoporosis-related fractures in an older Mediterranean population who are at high risk for cardiovascular events. Similar data were reported by Nouri and coauthors in a study from Iran.

The quantity and quality of dietary carbohydrates may also have an impact on bone. The quality of carbohydrates has been assessed using the carbohydrate quality index (CQI) and the low carbohydrate diet score (LCDS). The CQI takes into account dietary fiber intake, glycemic index, intake of processed vs. whole grain, and solid vs. total carbohydrates in diet. A higher CQI diet is associated with reduced cardiovascular risk. Higher LCDS reflects lower carbohydrate and higher fat and protein intake.

Diets that are rich in refined or processed carbohydrates with added sugar are proinflammatory and increase oxidative stress, which may lead to increased bone loss, low bone density, and increased fracture risk. These foods also have a high glycemic index.

In contrast, diets that are rich in whole grains, legumes, fruits, vegetables, nuts, and olive oil have a lower glycemic index and are beneficial to bone. These diets have a higher CQI and LCDS (as reported by Nouri and coauthors) and provide a rich source of antioxidants, vitamins, minerals, and other nutrients (such as calcium, magnesium, and vitamins B, C, and K), which are all beneficial to bone. Gao and others have reported that implementing a low glycemic index pulse-based diet (lentils, peas, beans) is superior to a regular hospital diet in preventing the increase in bone loss that typically occurs during hospitalization with enforced bed rest.

Most reports of the impact of carbohydrates on bone health are from observational studies. In an interventional study, Dalskov and coauthors randomly assigned children aged 5-18 years who had parents with overweight to one of five diets (high protein/low glycemic index, high protein/high glycemic index, low protein/low glycemic index, low protein/high glycemic index, or regular) for 6 months.

Contrasting with our understanding that protein intake is overall good for bone, this study found that among patients receiving a high–glycemic index diet, those who were on a high-protein diet had greater reductions in a bone formation marker than did those on a low-protein diet, with no major changes observed with the other diets. This suggests the influence of associated dietary nutrients on bone outcomes and that protein intake may modify the effects of dietary carbohydrates on bone formation. Similarly, the fat content of food can alter the glycemic index and thus may modify the impact of dietary carbohydrates on bone.

In summary, available data suggest that the quantity and quality of carbohydrates, including the glycemic index of food, may affect bone health and that it is important to exercise moderation in the consumption of such foods. However, there are only a few studies that have examined these associations, and more studies are necessary to further clarify the impact of dietary carbohydrates on bone as well as any modifications of these effects by other associated food groups. These studies will allow us to refine our recommendations to our patients as we advance our understanding of the impact of the combined effects of various dietary nutrients on bone.

Madhusmita Misra, MD, MPH, is chief of the division of pediatric endocrinology, Mass General for Children, Boston, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for AbbVie, Sanofi, and Ipsen.

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

Giving pembrolizumab (Keytruda) both before and after surgery for advanced melanoma significantly improves event-free survival, show results from the phase 2 SWOG S1801 trial.

The trial involved 319 patients with operable stage IIIB to stage IV melanoma. The investigators found that patients who received pembrolizumab both before and after surgery (i.e., neoadjuvant and adjuvant therapy) fared better than those who received the drug only after surgery: The 2-year event-free survival rates were 72% vs. 49%, respectively.

The research was published in the New England Journal of Medicine, but similar results had already been presented at the European Society for Medical Oncology 2022 annual Meeting.

“It’s not just what you give; it’s when you give it,” said lead author Sapna Patel, MD, in a press release issued by the University of Texas MD Anderson Cancer Center, echoing comments she gave at ESMO 2022.

The study, she continued, “demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes.”

On the basis of their findings, Dr. Patel, who is associate professor of melanoma medical oncology at the University of Texas MD Anderson Cancer Center, Houston, said that patients with high-risk melanoma “should start immunotherapy prior to surgery to generate an immune response while the bulk of the melanoma and the anti-tumor T cells are intact.”

The mechanism of action of PD-1 blockade “relies on the presence of preexisting anti-tumor T cells attempting to attack cancer cells,” with the immunotherapy allowing the anti-tumor cells to proliferate and mediate clinical responses.

Resection of the bulk of the tumor is therefore “likely to take away some or even most of the potential anti-tumor T cells that would proliferate after PD-1 blockade,” they write.
 

Likely to apply also to nivolumab

Approached for comment, Jeffrey S. Weber, MD, PhD, professor of medicine, NYU Langone Medical Center, New York, said that outside of trials, both pembrolizumab and ipilimumab (Yervoy)/nivolumab (Opdivo) are already being used neoadjuvantly.

He thinks that the findings for neoadjuvant and adjuvant pembrolizumab could also apply to nivolumab because “the drugs are quite similar in efficacy.”

Dr. Weber told this news organization that, “even though the S1801 trial was not accepted as a registration trial by the FDA, I think that its results could very well change practice and confirm it for others who already use neoadjuvant therapy for palpable stage III melanoma.”

One question that is being addressed to an extent in the NADINA trial is whether adjuvant immunotherapy can be avoided all together and patients receive only neoadjuvant therapy, although Dr. Weber said, “I doubt that will be the case.”

Study details

In this study, patients were randomly assigned to either surgery followed by 18 doses of adjuvant pembrolizumab, or to receive 3 doses of neoadjuvant pembrolizumab followed by surgery and then 15 additional doses of adjuvant pembrolizumab.

After a median duration of follow-up of 14.7 months, there were 38 events in the neoadjuvant-adjuvant group and 67 in the adjuvant-only group.

“Events” were defined as disease progression, toxic effects, or complications that precluded surgery or the initiation of adjuvant therapy within 84 days of surgery, as well as the inability to fully resect the gross disease, melanoma recurrence, and death.

The team calculated that event-free survival was significantly longer in the neoadjuvant-adjuvant group (P = .004), with 2-year event-free survival at 72% vs. 49% in the adjuvant-only group.

“The benefit of neoadjuvant pembrolizumab was seen across all subgroups of patients,” the investigators note.

At the data cut-off, there were 14 deaths in the neoadjuvant-adjuvant group vs. 22 in the adjuvant-only group, which the researchers say is too few to allow “definitive comparison” in terms of overall survival.

Definitive surgery had been performed in 88% of neoadjuvant-adjuvant patients and in 95% of those assigned to adjuvant-only pembrolizumab. The most common reason for not undergoing surgery was disease progression.

Among the patients for whom safety data were available, 7% in the neoadjuvant-adjuvant group had at least one grade 3 or 4 adverse event related to pembrolizumab, whereas 7% had at least one grade 3 or 4 adverse event related to surgery.

In the adjuvant-only arm, 4% of patients had at least one grade 3 adverse event related to surgery, with no grade 4 adverse events reported.

The rates of grade 3 or 4 adverse events during adjuvant therapy were similar in the two groups, at 12% in patients assigned to neoadjuvant-adjuvant therapy and 14% in those given adjuvant-only pembrolizumab.

“Future studies can explore deescalation strategies for both surgery and adjuvant therapy, as well as approaches for patients whose melanoma does not respond to neoadjuvant therapy,” the researchers commented.

The study was funded by the National Cancer Institute and Merck Sharp and Dohme.

Dr. Patel reports numerous relationships with industry, including with Merck, manufacturer of pembrolizumab; other coauthors also have numerous relationships with industry. Dr. Weber is a regular columnist for this news organization and lists his disclosures in his Weber on Oncology column.

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

Giving pembrolizumab (Keytruda) both before and after surgery for advanced melanoma significantly improves event-free survival, show results from the phase 2 SWOG S1801 trial.

The trial involved 319 patients with operable stage IIIB to stage IV melanoma. The investigators found that patients who received pembrolizumab both before and after surgery (i.e., neoadjuvant and adjuvant therapy) fared better than those who received the drug only after surgery: The 2-year event-free survival rates were 72% vs. 49%, respectively.

The research was published in the New England Journal of Medicine, but similar results had already been presented at the European Society for Medical Oncology 2022 annual Meeting.

“It’s not just what you give; it’s when you give it,” said lead author Sapna Patel, MD, in a press release issued by the University of Texas MD Anderson Cancer Center, echoing comments she gave at ESMO 2022.

The study, she continued, “demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes.”

On the basis of their findings, Dr. Patel, who is associate professor of melanoma medical oncology at the University of Texas MD Anderson Cancer Center, Houston, said that patients with high-risk melanoma “should start immunotherapy prior to surgery to generate an immune response while the bulk of the melanoma and the anti-tumor T cells are intact.”

The mechanism of action of PD-1 blockade “relies on the presence of preexisting anti-tumor T cells attempting to attack cancer cells,” with the immunotherapy allowing the anti-tumor cells to proliferate and mediate clinical responses.

Resection of the bulk of the tumor is therefore “likely to take away some or even most of the potential anti-tumor T cells that would proliferate after PD-1 blockade,” they write.
 

Likely to apply also to nivolumab

Approached for comment, Jeffrey S. Weber, MD, PhD, professor of medicine, NYU Langone Medical Center, New York, said that outside of trials, both pembrolizumab and ipilimumab (Yervoy)/nivolumab (Opdivo) are already being used neoadjuvantly.

He thinks that the findings for neoadjuvant and adjuvant pembrolizumab could also apply to nivolumab because “the drugs are quite similar in efficacy.”

Dr. Weber told this news organization that, “even though the S1801 trial was not accepted as a registration trial by the FDA, I think that its results could very well change practice and confirm it for others who already use neoadjuvant therapy for palpable stage III melanoma.”

One question that is being addressed to an extent in the NADINA trial is whether adjuvant immunotherapy can be avoided all together and patients receive only neoadjuvant therapy, although Dr. Weber said, “I doubt that will be the case.”

Study details

In this study, patients were randomly assigned to either surgery followed by 18 doses of adjuvant pembrolizumab, or to receive 3 doses of neoadjuvant pembrolizumab followed by surgery and then 15 additional doses of adjuvant pembrolizumab.

After a median duration of follow-up of 14.7 months, there were 38 events in the neoadjuvant-adjuvant group and 67 in the adjuvant-only group.

“Events” were defined as disease progression, toxic effects, or complications that precluded surgery or the initiation of adjuvant therapy within 84 days of surgery, as well as the inability to fully resect the gross disease, melanoma recurrence, and death.

The team calculated that event-free survival was significantly longer in the neoadjuvant-adjuvant group (P = .004), with 2-year event-free survival at 72% vs. 49% in the adjuvant-only group.

“The benefit of neoadjuvant pembrolizumab was seen across all subgroups of patients,” the investigators note.

At the data cut-off, there were 14 deaths in the neoadjuvant-adjuvant group vs. 22 in the adjuvant-only group, which the researchers say is too few to allow “definitive comparison” in terms of overall survival.

Definitive surgery had been performed in 88% of neoadjuvant-adjuvant patients and in 95% of those assigned to adjuvant-only pembrolizumab. The most common reason for not undergoing surgery was disease progression.

Among the patients for whom safety data were available, 7% in the neoadjuvant-adjuvant group had at least one grade 3 or 4 adverse event related to pembrolizumab, whereas 7% had at least one grade 3 or 4 adverse event related to surgery.

In the adjuvant-only arm, 4% of patients had at least one grade 3 adverse event related to surgery, with no grade 4 adverse events reported.

The rates of grade 3 or 4 adverse events during adjuvant therapy were similar in the two groups, at 12% in patients assigned to neoadjuvant-adjuvant therapy and 14% in those given adjuvant-only pembrolizumab.

“Future studies can explore deescalation strategies for both surgery and adjuvant therapy, as well as approaches for patients whose melanoma does not respond to neoadjuvant therapy,” the researchers commented.

The study was funded by the National Cancer Institute and Merck Sharp and Dohme.

Dr. Patel reports numerous relationships with industry, including with Merck, manufacturer of pembrolizumab; other coauthors also have numerous relationships with industry. Dr. Weber is a regular columnist for this news organization and lists his disclosures in his Weber on Oncology column.

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

Giving pembrolizumab (Keytruda) both before and after surgery for advanced melanoma significantly improves event-free survival, show results from the phase 2 SWOG S1801 trial.

The trial involved 319 patients with operable stage IIIB to stage IV melanoma. The investigators found that patients who received pembrolizumab both before and after surgery (i.e., neoadjuvant and adjuvant therapy) fared better than those who received the drug only after surgery: The 2-year event-free survival rates were 72% vs. 49%, respectively.

The research was published in the New England Journal of Medicine, but similar results had already been presented at the European Society for Medical Oncology 2022 annual Meeting.

“It’s not just what you give; it’s when you give it,” said lead author Sapna Patel, MD, in a press release issued by the University of Texas MD Anderson Cancer Center, echoing comments she gave at ESMO 2022.

The study, she continued, “demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes.”

On the basis of their findings, Dr. Patel, who is associate professor of melanoma medical oncology at the University of Texas MD Anderson Cancer Center, Houston, said that patients with high-risk melanoma “should start immunotherapy prior to surgery to generate an immune response while the bulk of the melanoma and the anti-tumor T cells are intact.”

The mechanism of action of PD-1 blockade “relies on the presence of preexisting anti-tumor T cells attempting to attack cancer cells,” with the immunotherapy allowing the anti-tumor cells to proliferate and mediate clinical responses.

Resection of the bulk of the tumor is therefore “likely to take away some or even most of the potential anti-tumor T cells that would proliferate after PD-1 blockade,” they write.
 

Likely to apply also to nivolumab

Approached for comment, Jeffrey S. Weber, MD, PhD, professor of medicine, NYU Langone Medical Center, New York, said that outside of trials, both pembrolizumab and ipilimumab (Yervoy)/nivolumab (Opdivo) are already being used neoadjuvantly.

He thinks that the findings for neoadjuvant and adjuvant pembrolizumab could also apply to nivolumab because “the drugs are quite similar in efficacy.”

Dr. Weber told this news organization that, “even though the S1801 trial was not accepted as a registration trial by the FDA, I think that its results could very well change practice and confirm it for others who already use neoadjuvant therapy for palpable stage III melanoma.”

One question that is being addressed to an extent in the NADINA trial is whether adjuvant immunotherapy can be avoided all together and patients receive only neoadjuvant therapy, although Dr. Weber said, “I doubt that will be the case.”

Study details

In this study, patients were randomly assigned to either surgery followed by 18 doses of adjuvant pembrolizumab, or to receive 3 doses of neoadjuvant pembrolizumab followed by surgery and then 15 additional doses of adjuvant pembrolizumab.

After a median duration of follow-up of 14.7 months, there were 38 events in the neoadjuvant-adjuvant group and 67 in the adjuvant-only group.

“Events” were defined as disease progression, toxic effects, or complications that precluded surgery or the initiation of adjuvant therapy within 84 days of surgery, as well as the inability to fully resect the gross disease, melanoma recurrence, and death.

The team calculated that event-free survival was significantly longer in the neoadjuvant-adjuvant group (P = .004), with 2-year event-free survival at 72% vs. 49% in the adjuvant-only group.

“The benefit of neoadjuvant pembrolizumab was seen across all subgroups of patients,” the investigators note.

At the data cut-off, there were 14 deaths in the neoadjuvant-adjuvant group vs. 22 in the adjuvant-only group, which the researchers say is too few to allow “definitive comparison” in terms of overall survival.

Definitive surgery had been performed in 88% of neoadjuvant-adjuvant patients and in 95% of those assigned to adjuvant-only pembrolizumab. The most common reason for not undergoing surgery was disease progression.

Among the patients for whom safety data were available, 7% in the neoadjuvant-adjuvant group had at least one grade 3 or 4 adverse event related to pembrolizumab, whereas 7% had at least one grade 3 or 4 adverse event related to surgery.

In the adjuvant-only arm, 4% of patients had at least one grade 3 adverse event related to surgery, with no grade 4 adverse events reported.

The rates of grade 3 or 4 adverse events during adjuvant therapy were similar in the two groups, at 12% in patients assigned to neoadjuvant-adjuvant therapy and 14% in those given adjuvant-only pembrolizumab.

“Future studies can explore deescalation strategies for both surgery and adjuvant therapy, as well as approaches for patients whose melanoma does not respond to neoadjuvant therapy,” the researchers commented.

The study was funded by the National Cancer Institute and Merck Sharp and Dohme.

Dr. Patel reports numerous relationships with industry, including with Merck, manufacturer of pembrolizumab; other coauthors also have numerous relationships with industry. Dr. Weber is a regular columnist for this news organization and lists his disclosures in his Weber on Oncology column.

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