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Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

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

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

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

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

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

In one of several recently published studies on the relationship between COVID-19 infection and asthma, asthma symptoms in children declined as the proportion of the US population vaccinated against COVID-19 increased, according to data drawn from the National Survey of Children’s Health (NSCH).

The inverse correlation between symptoms and vaccination was strong and statistically significant, according to investigators led by Matthew M. Davis, MD, Physician in Chief and Chief Scientific Officer, Nemours Children’s Health, Wilmington, Delaware.

“With each increase of 10 percentage points in COVID-19 vaccination coverage, the parent-reported child asthma symptoms prevalence decreased by 0.36 percentage points (P < .05),” Dr. Davis and his coinvestigators reported in a research letter published in JAMA Network Open.
 

Studies Explore Relationship of COVID and Asthma

The reduced risk of asthma symptoms with COVID-19 vaccination in children at the population level is just one of several recently published studies exploring the interaction between COVID-19 infection and asthma, but two studies that posed the same question did not reach the same conclusion.

In one, COVID-19 infection in children was not found to be a trigger for new-onset asthma, but the second found that it was. In a third study, the preponderance of evidence from a meta-analysis found that patients with asthma – whether children or adults – did not necessarily experience a more severe course of COVID-19 infection than in those without asthma.

The NSCH database study calculated state-level change in scores for patient-reported childhood asthma symptoms in the years in the years 2018-2019, which preceded the pandemic and the years 2020-2021, when the pandemic began. The hypothesis was that the proportion of the population 5 years of age or older who completed the COVID-19 primary vaccination would be inversely related to asthma symptom prevalence.

Relative to the 2018-2019 years, the mean rate of parent-reported asthma symptoms was 0.85% lower (6.93% vs 7.77%; P < .001) in 2020-2021, when the mean primary series COVID-19 vaccination rate was 72.3%.

The study was not able to evaluate the impact of COVID-19 vaccination specifically in children with asthma, because history of asthma is not captured in the NSCH data, but Dr. Davis contended that the reduction in symptomatic asthma among children with increased vaccination offers validation for the state-level findings.

“Moreover, the absence of an association of COVID-19 vaccination administered predominantly in 2021 with population-level COVID-19 mortality in 2020 serves as a negative control,” he and his colleagues wrote in their research letter.
 

Protection from Respiratory Viruses Seen for Asthma Patients

In an interview, Dr. Davis reported that these data are consistent with previous evidence that immunization against influenza also reduces risk of asthma symptoms. In a meta-analysis published in 2017, it was estimated that live vaccines reduced risk of influenza by 81% and prevented 59%-72% of asthma attacks leading to hospitalizations or emergency room visits.

“The similarity of our findings regarding COVID-19 vaccination to prior data regarding influenza vaccination underscores the importance of preventing viral illnesses in individuals with a history of asthma,” Dr. Davis said. It is not yet clear if this is true of respiratory syncytial virus (RSV). Because of the short time that the RSV vaccine has been available, it is too soon to conduct an analysis.

One message from this study is that “clinicians should continue to encourage COVID-19 vaccination for children because of its general benefits in preventing coronavirus-related illness and the apparent specific benefits for children with a history of asthma,” he said.

While vaccination appears to reduce asthmatic symptoms related to COVID-19 infection, one study suggests that COVID-19 does not trigger new-onset asthma. In a retrospective study published in Pediatrics, no association between COVID-19 infection and new-onset asthma could be made in an analysis of 27,423 children (ages, 1-16 years) from the Children’s Hospital of Philadelphia (CHOP) Care Network.

Across all the pediatric age groups evaluated, the consistent finding was “SARS-CoV-2 positivity does not confer an additional risk for asthma diagnosis at least within the first 18 months after a [polymerase chain reaction] test,” concluded the investigators, led by David A. Hill, MD, PhD, Division of Allergy and Immunology, CHOP, Philadelphia, Pennsylvania.
 

Risk of Asthma Doubled After COVID-19 Infection

However, the opposite conclusion was reached by investigators evaluating data from two cohorts of children ages 5-18 drawn from the TriNetX database, a global health research network with data on more than 250 million individuals. Cohort 1 included more than 250,000 children. These children had never received COVID-19 vaccination. The 50,000 patients in cohort 2 had all received COVID19 vaccination.

To compare the impact of COVID-19 infection on new-onset asthma, the patients who were infected with COVID-19 were compared with those who were not infected after propensity score matching over 18 months of follow-up.

In cohort 1, the rate of new onset asthma was more than twofold greater among those with COVID-19 infection (4.7% vs 2.0%). The hazard ratio (HR) of 2.25 had tight confidence intervals (95% CI, 2.158-2.367).

In cohort 2, the risk of new-onset asthma at 18 months among those who had a COVID-19 infection relative to those without was even greater (8.3% vs 3.1%). The relative risk approached a 3-fold increase (HR 2.745; 95% CI, 2.521-2.99).

The conclusion of these investigators, led by Chia-Chi Lung, PhD, Department of Public Health, Chung Shan Medical University, Taichung City, Taiwan, was that there is “a critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children.”

These health risks might not be as significant as once feared. In the recently published study from Environmental Health Insights, the goal of a meta-analysis was to determine if patients with asthma relative to those without asthma face a higher risk of serious disease from COVID-19 infection. The meta-analysis included studies of children and adults. The answer, according an in-depth analysis of 21 articles in a “scoping review,” was a qualified no.

Of the 21 articles, 4 concluded that asthma is a risk factor for serious COVID-19 infection, but 17 did not, according to Chukwudi S. Ubah, PhD, Department of Public Health, Brody School of Medicine, East Caroline University, Greenville, North Carolina.
 

None of These Questions are Fully Resolved

However, given the disparity in the results and the fact that many of the studies included in this analysis had small sample sizes, Dr. Ubah called for larger studies and studies with better controls. He noted, for example, that the studies did not consistently evaluate mitigating factors, such as used of inhaled or oral corticosteroids, which might affect risk of the severity of a COVID-19 infection.

Rather, “our findings pointed out that the type of medication prescribed for asthma may have implications for the severity of COVID-19 infection in these patients,” Dr. Ubah said in an interview.

Overall, the data do not support a major interaction between asthma and COVID-19, even if the data are not conclusive. Each of the senior authors of these studies called for larger and better investigations to further explore whether COVID-19 infection and preexisting asthma interact. So far, the data indicate that if COVID-19 infection poses a risk of precipitating new-onset asthma or inducing a more severe infection in children with asthma, it is low, but the degree of risk, if any, remains unresolved in subgroups defined by asthma treatment or asthma severity.

Dr. Davis, Dr. Hill, Dr. Lung, and Dr. Ubah reported no potential conflicts of interest. None of these studies received funding from commercial interests.

In one of several recently published studies on the relationship between COVID-19 infection and asthma, asthma symptoms in children declined as the proportion of the US population vaccinated against COVID-19 increased, according to data drawn from the National Survey of Children’s Health (NSCH).

The inverse correlation between symptoms and vaccination was strong and statistically significant, according to investigators led by Matthew M. Davis, MD, Physician in Chief and Chief Scientific Officer, Nemours Children’s Health, Wilmington, Delaware.

“With each increase of 10 percentage points in COVID-19 vaccination coverage, the parent-reported child asthma symptoms prevalence decreased by 0.36 percentage points (P < .05),” Dr. Davis and his coinvestigators reported in a research letter published in JAMA Network Open.
 

Studies Explore Relationship of COVID and Asthma

The reduced risk of asthma symptoms with COVID-19 vaccination in children at the population level is just one of several recently published studies exploring the interaction between COVID-19 infection and asthma, but two studies that posed the same question did not reach the same conclusion.

In one, COVID-19 infection in children was not found to be a trigger for new-onset asthma, but the second found that it was. In a third study, the preponderance of evidence from a meta-analysis found that patients with asthma – whether children or adults – did not necessarily experience a more severe course of COVID-19 infection than in those without asthma.

The NSCH database study calculated state-level change in scores for patient-reported childhood asthma symptoms in the years in the years 2018-2019, which preceded the pandemic and the years 2020-2021, when the pandemic began. The hypothesis was that the proportion of the population 5 years of age or older who completed the COVID-19 primary vaccination would be inversely related to asthma symptom prevalence.

Relative to the 2018-2019 years, the mean rate of parent-reported asthma symptoms was 0.85% lower (6.93% vs 7.77%; P < .001) in 2020-2021, when the mean primary series COVID-19 vaccination rate was 72.3%.

The study was not able to evaluate the impact of COVID-19 vaccination specifically in children with asthma, because history of asthma is not captured in the NSCH data, but Dr. Davis contended that the reduction in symptomatic asthma among children with increased vaccination offers validation for the state-level findings.

“Moreover, the absence of an association of COVID-19 vaccination administered predominantly in 2021 with population-level COVID-19 mortality in 2020 serves as a negative control,” he and his colleagues wrote in their research letter.
 

Protection from Respiratory Viruses Seen for Asthma Patients

In an interview, Dr. Davis reported that these data are consistent with previous evidence that immunization against influenza also reduces risk of asthma symptoms. In a meta-analysis published in 2017, it was estimated that live vaccines reduced risk of influenza by 81% and prevented 59%-72% of asthma attacks leading to hospitalizations or emergency room visits.

“The similarity of our findings regarding COVID-19 vaccination to prior data regarding influenza vaccination underscores the importance of preventing viral illnesses in individuals with a history of asthma,” Dr. Davis said. It is not yet clear if this is true of respiratory syncytial virus (RSV). Because of the short time that the RSV vaccine has been available, it is too soon to conduct an analysis.

One message from this study is that “clinicians should continue to encourage COVID-19 vaccination for children because of its general benefits in preventing coronavirus-related illness and the apparent specific benefits for children with a history of asthma,” he said.

While vaccination appears to reduce asthmatic symptoms related to COVID-19 infection, one study suggests that COVID-19 does not trigger new-onset asthma. In a retrospective study published in Pediatrics, no association between COVID-19 infection and new-onset asthma could be made in an analysis of 27,423 children (ages, 1-16 years) from the Children’s Hospital of Philadelphia (CHOP) Care Network.

Across all the pediatric age groups evaluated, the consistent finding was “SARS-CoV-2 positivity does not confer an additional risk for asthma diagnosis at least within the first 18 months after a [polymerase chain reaction] test,” concluded the investigators, led by David A. Hill, MD, PhD, Division of Allergy and Immunology, CHOP, Philadelphia, Pennsylvania.
 

Risk of Asthma Doubled After COVID-19 Infection

However, the opposite conclusion was reached by investigators evaluating data from two cohorts of children ages 5-18 drawn from the TriNetX database, a global health research network with data on more than 250 million individuals. Cohort 1 included more than 250,000 children. These children had never received COVID-19 vaccination. The 50,000 patients in cohort 2 had all received COVID19 vaccination.

To compare the impact of COVID-19 infection on new-onset asthma, the patients who were infected with COVID-19 were compared with those who were not infected after propensity score matching over 18 months of follow-up.

In cohort 1, the rate of new onset asthma was more than twofold greater among those with COVID-19 infection (4.7% vs 2.0%). The hazard ratio (HR) of 2.25 had tight confidence intervals (95% CI, 2.158-2.367).

In cohort 2, the risk of new-onset asthma at 18 months among those who had a COVID-19 infection relative to those without was even greater (8.3% vs 3.1%). The relative risk approached a 3-fold increase (HR 2.745; 95% CI, 2.521-2.99).

The conclusion of these investigators, led by Chia-Chi Lung, PhD, Department of Public Health, Chung Shan Medical University, Taichung City, Taiwan, was that there is “a critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children.”

These health risks might not be as significant as once feared. In the recently published study from Environmental Health Insights, the goal of a meta-analysis was to determine if patients with asthma relative to those without asthma face a higher risk of serious disease from COVID-19 infection. The meta-analysis included studies of children and adults. The answer, according an in-depth analysis of 21 articles in a “scoping review,” was a qualified no.

Of the 21 articles, 4 concluded that asthma is a risk factor for serious COVID-19 infection, but 17 did not, according to Chukwudi S. Ubah, PhD, Department of Public Health, Brody School of Medicine, East Caroline University, Greenville, North Carolina.
 

None of These Questions are Fully Resolved

However, given the disparity in the results and the fact that many of the studies included in this analysis had small sample sizes, Dr. Ubah called for larger studies and studies with better controls. He noted, for example, that the studies did not consistently evaluate mitigating factors, such as used of inhaled or oral corticosteroids, which might affect risk of the severity of a COVID-19 infection.

Rather, “our findings pointed out that the type of medication prescribed for asthma may have implications for the severity of COVID-19 infection in these patients,” Dr. Ubah said in an interview.

Overall, the data do not support a major interaction between asthma and COVID-19, even if the data are not conclusive. Each of the senior authors of these studies called for larger and better investigations to further explore whether COVID-19 infection and preexisting asthma interact. So far, the data indicate that if COVID-19 infection poses a risk of precipitating new-onset asthma or inducing a more severe infection in children with asthma, it is low, but the degree of risk, if any, remains unresolved in subgroups defined by asthma treatment or asthma severity.

Dr. Davis, Dr. Hill, Dr. Lung, and Dr. Ubah reported no potential conflicts of interest. None of these studies received funding from commercial interests.

In one of several recently published studies on the relationship between COVID-19 infection and asthma, asthma symptoms in children declined as the proportion of the US population vaccinated against COVID-19 increased, according to data drawn from the National Survey of Children’s Health (NSCH).

The inverse correlation between symptoms and vaccination was strong and statistically significant, according to investigators led by Matthew M. Davis, MD, Physician in Chief and Chief Scientific Officer, Nemours Children’s Health, Wilmington, Delaware.

“With each increase of 10 percentage points in COVID-19 vaccination coverage, the parent-reported child asthma symptoms prevalence decreased by 0.36 percentage points (P < .05),” Dr. Davis and his coinvestigators reported in a research letter published in JAMA Network Open.
 

Studies Explore Relationship of COVID and Asthma

The reduced risk of asthma symptoms with COVID-19 vaccination in children at the population level is just one of several recently published studies exploring the interaction between COVID-19 infection and asthma, but two studies that posed the same question did not reach the same conclusion.

In one, COVID-19 infection in children was not found to be a trigger for new-onset asthma, but the second found that it was. In a third study, the preponderance of evidence from a meta-analysis found that patients with asthma – whether children or adults – did not necessarily experience a more severe course of COVID-19 infection than in those without asthma.

The NSCH database study calculated state-level change in scores for patient-reported childhood asthma symptoms in the years in the years 2018-2019, which preceded the pandemic and the years 2020-2021, when the pandemic began. The hypothesis was that the proportion of the population 5 years of age or older who completed the COVID-19 primary vaccination would be inversely related to asthma symptom prevalence.

Relative to the 2018-2019 years, the mean rate of parent-reported asthma symptoms was 0.85% lower (6.93% vs 7.77%; P < .001) in 2020-2021, when the mean primary series COVID-19 vaccination rate was 72.3%.

The study was not able to evaluate the impact of COVID-19 vaccination specifically in children with asthma, because history of asthma is not captured in the NSCH data, but Dr. Davis contended that the reduction in symptomatic asthma among children with increased vaccination offers validation for the state-level findings.

“Moreover, the absence of an association of COVID-19 vaccination administered predominantly in 2021 with population-level COVID-19 mortality in 2020 serves as a negative control,” he and his colleagues wrote in their research letter.
 

Protection from Respiratory Viruses Seen for Asthma Patients

In an interview, Dr. Davis reported that these data are consistent with previous evidence that immunization against influenza also reduces risk of asthma symptoms. In a meta-analysis published in 2017, it was estimated that live vaccines reduced risk of influenza by 81% and prevented 59%-72% of asthma attacks leading to hospitalizations or emergency room visits.

“The similarity of our findings regarding COVID-19 vaccination to prior data regarding influenza vaccination underscores the importance of preventing viral illnesses in individuals with a history of asthma,” Dr. Davis said. It is not yet clear if this is true of respiratory syncytial virus (RSV). Because of the short time that the RSV vaccine has been available, it is too soon to conduct an analysis.

One message from this study is that “clinicians should continue to encourage COVID-19 vaccination for children because of its general benefits in preventing coronavirus-related illness and the apparent specific benefits for children with a history of asthma,” he said.

While vaccination appears to reduce asthmatic symptoms related to COVID-19 infection, one study suggests that COVID-19 does not trigger new-onset asthma. In a retrospective study published in Pediatrics, no association between COVID-19 infection and new-onset asthma could be made in an analysis of 27,423 children (ages, 1-16 years) from the Children’s Hospital of Philadelphia (CHOP) Care Network.

Across all the pediatric age groups evaluated, the consistent finding was “SARS-CoV-2 positivity does not confer an additional risk for asthma diagnosis at least within the first 18 months after a [polymerase chain reaction] test,” concluded the investigators, led by David A. Hill, MD, PhD, Division of Allergy and Immunology, CHOP, Philadelphia, Pennsylvania.
 

Risk of Asthma Doubled After COVID-19 Infection

However, the opposite conclusion was reached by investigators evaluating data from two cohorts of children ages 5-18 drawn from the TriNetX database, a global health research network with data on more than 250 million individuals. Cohort 1 included more than 250,000 children. These children had never received COVID-19 vaccination. The 50,000 patients in cohort 2 had all received COVID19 vaccination.

To compare the impact of COVID-19 infection on new-onset asthma, the patients who were infected with COVID-19 were compared with those who were not infected after propensity score matching over 18 months of follow-up.

In cohort 1, the rate of new onset asthma was more than twofold greater among those with COVID-19 infection (4.7% vs 2.0%). The hazard ratio (HR) of 2.25 had tight confidence intervals (95% CI, 2.158-2.367).

In cohort 2, the risk of new-onset asthma at 18 months among those who had a COVID-19 infection relative to those without was even greater (8.3% vs 3.1%). The relative risk approached a 3-fold increase (HR 2.745; 95% CI, 2.521-2.99).

The conclusion of these investigators, led by Chia-Chi Lung, PhD, Department of Public Health, Chung Shan Medical University, Taichung City, Taiwan, was that there is “a critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children.”

These health risks might not be as significant as once feared. In the recently published study from Environmental Health Insights, the goal of a meta-analysis was to determine if patients with asthma relative to those without asthma face a higher risk of serious disease from COVID-19 infection. The meta-analysis included studies of children and adults. The answer, according an in-depth analysis of 21 articles in a “scoping review,” was a qualified no.

Of the 21 articles, 4 concluded that asthma is a risk factor for serious COVID-19 infection, but 17 did not, according to Chukwudi S. Ubah, PhD, Department of Public Health, Brody School of Medicine, East Caroline University, Greenville, North Carolina.
 

None of These Questions are Fully Resolved

However, given the disparity in the results and the fact that many of the studies included in this analysis had small sample sizes, Dr. Ubah called for larger studies and studies with better controls. He noted, for example, that the studies did not consistently evaluate mitigating factors, such as used of inhaled or oral corticosteroids, which might affect risk of the severity of a COVID-19 infection.

Rather, “our findings pointed out that the type of medication prescribed for asthma may have implications for the severity of COVID-19 infection in these patients,” Dr. Ubah said in an interview.

Overall, the data do not support a major interaction between asthma and COVID-19, even if the data are not conclusive. Each of the senior authors of these studies called for larger and better investigations to further explore whether COVID-19 infection and preexisting asthma interact. So far, the data indicate that if COVID-19 infection poses a risk of precipitating new-onset asthma or inducing a more severe infection in children with asthma, it is low, but the degree of risk, if any, remains unresolved in subgroups defined by asthma treatment or asthma severity.

Dr. Davis, Dr. Hill, Dr. Lung, and Dr. Ubah reported no potential conflicts of interest. None of these studies received funding from commercial interests.

Patients with atrial fibrillation who discontinued anticoagulation (OAC) therapy after an ischemic stroke faced double the risk of a recurrent stroke within 1 year compared with counterparts who didn’t stop the drugs, a new Danish nationwide cohort study finds.

Among 8,119 patients aged 50 years and older (54.1% male, mean age 78.4), 4.3% had a recurrent stroke within 1 year following discharge for the initial stroke, reported David Gaist, PhD, of Odense University Hospital, Odense, Denmark, and colleagues in JAMA Neurology.

An adjusted analysis found that those who stopped therapy were more than twice as likely to experience another stroke over a mean 2.9 years (13.4% vs 6.8%, adjusted odds ratio [aOR] = 2.13; 95% confidence interval [CI], 1.57-2.89).

The findings highlight the preventive power of OAC therapy, Dr. Gaist said in an interview, and point to the importance of counseling patients about the benefits of the drugs. “Clinicians can provide balanced information on the pros and cons of discontinuing oral anticoagulants as well as lay out plans on when to restart the medication,” he said.

The researchers launched the study “to provide data on how often recurrent ischemic strokes occur in a large, unselected cohort of patients with atrial fibrillation who had a stroke and started or restarted oral anticoagulants, a situation mirroring what we see in our everyday lives as clinicians,” Dr. Gaist said. “We also wanted to see if patients with breakthrough strokes had particular characteristics compared with patients who did not have a recurrent stroke. Finally, we wanted to quantify a very simple cause of breakthrough stroke by answering the following question: How many of these patients had stopped taking their oral anticoagulant?”
 

A Large, Unselected Patient Cohort

Dr. Gaist and colleagues tracked 8,119 patients with ischemic stroke and atrial fibrillation who started or restarted OAC therapy within 30 days following their discharge between 2014 and 2021. Patients either had atrial fibrillation before their stroke or developed it afterward.

Eighty-one percent of patients had hypertension, 19.7% had diabetes, and 27.3% had ischemic heart disease; 35.3% had never smoked and smoking information was missing for 15.9%. Race/ethnicity information was not provided.

Patients were followed for an average of 2.9 years until 2022, and all were alive at least 30 days after discharge. During that time, 663 patients had a recurrent ischemic stroke (4.3%), of whom 80.4% were on OAC therapy. The percentage who had stroke at 2 years rose to 6.5%.

While the researchers thought the number of strokes was high, Dr. Gaist said, this isn’t a sign that the drugs aren’t working. “Oral anticoagulant use in secondary prevention in atrial fibrillation is guideline-supported as it has been proven to reduce the risk of stroke by roughly two thirds.”

Of study participants at baseline, 37.9% took oral anticoagulants, 23.5% took direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban), and 15.1% took vitamin K antagonists. In a nested case-control analysis of 663 cases (58.7% men, mean age 80.1) matched to 2,652 controls, at admission for ischemic stroke, 80.4% were on OAC therapy, and 8%-11% of patients stopped OAC therapy after their strokes, the researchers reported.

Patients who stopped OAC therapy had more severe strokes than those who didn’t at 7 days (median recurrent ischemic stroke Scandinavian Stroke Scale [SSS] score = 40.0 vs 46.0, respectively; aOR = 2.10; 95% CI, 1.31-3.36). Those who stopped OAC therapy also had higher mortality rates at 7 days (11.2% vs 3.9%, respectively) and 30 days (28.1% vs 10.9%, respectively).

It’s not clear why some patients discontinued OAC therapy. “We looked for evidence of serious bleeding or surgical procedures around the time of anticoagulant discontinuation but found this only to be the case in roughly 10% of these patients,” Dr. Gaist said.

He added that the study probably “underestimates the issue of anticoagulant discontinuation, particularly for DOACs, where a shorter half-life compared with warfarin means that even a short drug-break of a few days puts the patient at increased risk of stroke.”

The authors noted study limitations, including the lack of data on actual medication usage, alcohol usage, stroke etiology, lesion location, and socioeconomic status. And, they wrote, the study population is mostly of European origin.
 

No Surprises

Steven R. Messe, MD, professor of neurology at the Hospital of the University of Pennsylvania, Philadelphia, who didn’t take part in the study but is familiar with its findings, said in an interview that the study is a “well-done analysis.”

The findings are not surprising, he said. “The overall risk of stroke recurrence was 4.3% at 1 year while the mortality rate was higher at 15.4%. Given that the median CHA₂DS₂-VASc score was 4 and the average age was 79, the stroke recurrence rate and mortality rate are in line with prior studies.”

In regard to the power of OAC therapy to prevent recurrent strokes, Dr. Messe noted that patients may not be adhering to prescribed regimens. Also, “while DOACs are clearly safer that vitamin K–dependent anticoagulants, the medications are generally not dose adjusted. It is possible that adjusting the dose based on measured anti-Xa levels to insure therapeutic anticoagulant effects may reduce the stroke risk further.”

He added that “most of these patients with prior stroke and atrial fibrillation are vasculopathic and at risk of additional strokes due to other mechanisms such as small vessel or large vessel disease.”

In the big picture, the study “confirms again that anticoagulation should be prescribed to all patients with atrial fibrillation and prior stroke, unless there is a strong bleeding risk contraindication,” Dr. Messe said. These patients are clearly at high risk of stroke recurrence and mortality, and all risk factors should be aggressively managed.”

Researchers are exploring other options, he said. “For example, there are studies of factor XI inhibitors that could be added to a DOAC for additional reductions in ischemic stroke. In addition, in patients undergoing cardiac surgery, the randomized trial LAOS III demonstrated that surgical left atrial occlusion in addition to anticoagulation may provide additional stroke prevention.”

Dr. Gaist disclosed personal fees from Pfizer and Bristol Myers Squibb, and grants from Bayer. Several other authors reported various relationships with industry. Dr. Messe has no disclosures.
 

Patients with atrial fibrillation who discontinued anticoagulation (OAC) therapy after an ischemic stroke faced double the risk of a recurrent stroke within 1 year compared with counterparts who didn’t stop the drugs, a new Danish nationwide cohort study finds.

Among 8,119 patients aged 50 years and older (54.1% male, mean age 78.4), 4.3% had a recurrent stroke within 1 year following discharge for the initial stroke, reported David Gaist, PhD, of Odense University Hospital, Odense, Denmark, and colleagues in JAMA Neurology.

An adjusted analysis found that those who stopped therapy were more than twice as likely to experience another stroke over a mean 2.9 years (13.4% vs 6.8%, adjusted odds ratio [aOR] = 2.13; 95% confidence interval [CI], 1.57-2.89).

The findings highlight the preventive power of OAC therapy, Dr. Gaist said in an interview, and point to the importance of counseling patients about the benefits of the drugs. “Clinicians can provide balanced information on the pros and cons of discontinuing oral anticoagulants as well as lay out plans on when to restart the medication,” he said.

The researchers launched the study “to provide data on how often recurrent ischemic strokes occur in a large, unselected cohort of patients with atrial fibrillation who had a stroke and started or restarted oral anticoagulants, a situation mirroring what we see in our everyday lives as clinicians,” Dr. Gaist said. “We also wanted to see if patients with breakthrough strokes had particular characteristics compared with patients who did not have a recurrent stroke. Finally, we wanted to quantify a very simple cause of breakthrough stroke by answering the following question: How many of these patients had stopped taking their oral anticoagulant?”
 

A Large, Unselected Patient Cohort

Dr. Gaist and colleagues tracked 8,119 patients with ischemic stroke and atrial fibrillation who started or restarted OAC therapy within 30 days following their discharge between 2014 and 2021. Patients either had atrial fibrillation before their stroke or developed it afterward.

Eighty-one percent of patients had hypertension, 19.7% had diabetes, and 27.3% had ischemic heart disease; 35.3% had never smoked and smoking information was missing for 15.9%. Race/ethnicity information was not provided.

Patients were followed for an average of 2.9 years until 2022, and all were alive at least 30 days after discharge. During that time, 663 patients had a recurrent ischemic stroke (4.3%), of whom 80.4% were on OAC therapy. The percentage who had stroke at 2 years rose to 6.5%.

While the researchers thought the number of strokes was high, Dr. Gaist said, this isn’t a sign that the drugs aren’t working. “Oral anticoagulant use in secondary prevention in atrial fibrillation is guideline-supported as it has been proven to reduce the risk of stroke by roughly two thirds.”

Of study participants at baseline, 37.9% took oral anticoagulants, 23.5% took direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban), and 15.1% took vitamin K antagonists. In a nested case-control analysis of 663 cases (58.7% men, mean age 80.1) matched to 2,652 controls, at admission for ischemic stroke, 80.4% were on OAC therapy, and 8%-11% of patients stopped OAC therapy after their strokes, the researchers reported.

Patients who stopped OAC therapy had more severe strokes than those who didn’t at 7 days (median recurrent ischemic stroke Scandinavian Stroke Scale [SSS] score = 40.0 vs 46.0, respectively; aOR = 2.10; 95% CI, 1.31-3.36). Those who stopped OAC therapy also had higher mortality rates at 7 days (11.2% vs 3.9%, respectively) and 30 days (28.1% vs 10.9%, respectively).

It’s not clear why some patients discontinued OAC therapy. “We looked for evidence of serious bleeding or surgical procedures around the time of anticoagulant discontinuation but found this only to be the case in roughly 10% of these patients,” Dr. Gaist said.

He added that the study probably “underestimates the issue of anticoagulant discontinuation, particularly for DOACs, where a shorter half-life compared with warfarin means that even a short drug-break of a few days puts the patient at increased risk of stroke.”

The authors noted study limitations, including the lack of data on actual medication usage, alcohol usage, stroke etiology, lesion location, and socioeconomic status. And, they wrote, the study population is mostly of European origin.
 

No Surprises

Steven R. Messe, MD, professor of neurology at the Hospital of the University of Pennsylvania, Philadelphia, who didn’t take part in the study but is familiar with its findings, said in an interview that the study is a “well-done analysis.”

The findings are not surprising, he said. “The overall risk of stroke recurrence was 4.3% at 1 year while the mortality rate was higher at 15.4%. Given that the median CHA₂DS₂-VASc score was 4 and the average age was 79, the stroke recurrence rate and mortality rate are in line with prior studies.”

In regard to the power of OAC therapy to prevent recurrent strokes, Dr. Messe noted that patients may not be adhering to prescribed regimens. Also, “while DOACs are clearly safer that vitamin K–dependent anticoagulants, the medications are generally not dose adjusted. It is possible that adjusting the dose based on measured anti-Xa levels to insure therapeutic anticoagulant effects may reduce the stroke risk further.”

He added that “most of these patients with prior stroke and atrial fibrillation are vasculopathic and at risk of additional strokes due to other mechanisms such as small vessel or large vessel disease.”

In the big picture, the study “confirms again that anticoagulation should be prescribed to all patients with atrial fibrillation and prior stroke, unless there is a strong bleeding risk contraindication,” Dr. Messe said. These patients are clearly at high risk of stroke recurrence and mortality, and all risk factors should be aggressively managed.”

Researchers are exploring other options, he said. “For example, there are studies of factor XI inhibitors that could be added to a DOAC for additional reductions in ischemic stroke. In addition, in patients undergoing cardiac surgery, the randomized trial LAOS III demonstrated that surgical left atrial occlusion in addition to anticoagulation may provide additional stroke prevention.”

Dr. Gaist disclosed personal fees from Pfizer and Bristol Myers Squibb, and grants from Bayer. Several other authors reported various relationships with industry. Dr. Messe has no disclosures.
 

Patients with atrial fibrillation who discontinued anticoagulation (OAC) therapy after an ischemic stroke faced double the risk of a recurrent stroke within 1 year compared with counterparts who didn’t stop the drugs, a new Danish nationwide cohort study finds.

Among 8,119 patients aged 50 years and older (54.1% male, mean age 78.4), 4.3% had a recurrent stroke within 1 year following discharge for the initial stroke, reported David Gaist, PhD, of Odense University Hospital, Odense, Denmark, and colleagues in JAMA Neurology.

An adjusted analysis found that those who stopped therapy were more than twice as likely to experience another stroke over a mean 2.9 years (13.4% vs 6.8%, adjusted odds ratio [aOR] = 2.13; 95% confidence interval [CI], 1.57-2.89).

The findings highlight the preventive power of OAC therapy, Dr. Gaist said in an interview, and point to the importance of counseling patients about the benefits of the drugs. “Clinicians can provide balanced information on the pros and cons of discontinuing oral anticoagulants as well as lay out plans on when to restart the medication,” he said.

The researchers launched the study “to provide data on how often recurrent ischemic strokes occur in a large, unselected cohort of patients with atrial fibrillation who had a stroke and started or restarted oral anticoagulants, a situation mirroring what we see in our everyday lives as clinicians,” Dr. Gaist said. “We also wanted to see if patients with breakthrough strokes had particular characteristics compared with patients who did not have a recurrent stroke. Finally, we wanted to quantify a very simple cause of breakthrough stroke by answering the following question: How many of these patients had stopped taking their oral anticoagulant?”
 

A Large, Unselected Patient Cohort

Dr. Gaist and colleagues tracked 8,119 patients with ischemic stroke and atrial fibrillation who started or restarted OAC therapy within 30 days following their discharge between 2014 and 2021. Patients either had atrial fibrillation before their stroke or developed it afterward.

Eighty-one percent of patients had hypertension, 19.7% had diabetes, and 27.3% had ischemic heart disease; 35.3% had never smoked and smoking information was missing for 15.9%. Race/ethnicity information was not provided.

Patients were followed for an average of 2.9 years until 2022, and all were alive at least 30 days after discharge. During that time, 663 patients had a recurrent ischemic stroke (4.3%), of whom 80.4% were on OAC therapy. The percentage who had stroke at 2 years rose to 6.5%.

While the researchers thought the number of strokes was high, Dr. Gaist said, this isn’t a sign that the drugs aren’t working. “Oral anticoagulant use in secondary prevention in atrial fibrillation is guideline-supported as it has been proven to reduce the risk of stroke by roughly two thirds.”

Of study participants at baseline, 37.9% took oral anticoagulants, 23.5% took direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban), and 15.1% took vitamin K antagonists. In a nested case-control analysis of 663 cases (58.7% men, mean age 80.1) matched to 2,652 controls, at admission for ischemic stroke, 80.4% were on OAC therapy, and 8%-11% of patients stopped OAC therapy after their strokes, the researchers reported.

Patients who stopped OAC therapy had more severe strokes than those who didn’t at 7 days (median recurrent ischemic stroke Scandinavian Stroke Scale [SSS] score = 40.0 vs 46.0, respectively; aOR = 2.10; 95% CI, 1.31-3.36). Those who stopped OAC therapy also had higher mortality rates at 7 days (11.2% vs 3.9%, respectively) and 30 days (28.1% vs 10.9%, respectively).

It’s not clear why some patients discontinued OAC therapy. “We looked for evidence of serious bleeding or surgical procedures around the time of anticoagulant discontinuation but found this only to be the case in roughly 10% of these patients,” Dr. Gaist said.

He added that the study probably “underestimates the issue of anticoagulant discontinuation, particularly for DOACs, where a shorter half-life compared with warfarin means that even a short drug-break of a few days puts the patient at increased risk of stroke.”

The authors noted study limitations, including the lack of data on actual medication usage, alcohol usage, stroke etiology, lesion location, and socioeconomic status. And, they wrote, the study population is mostly of European origin.
 

No Surprises

Steven R. Messe, MD, professor of neurology at the Hospital of the University of Pennsylvania, Philadelphia, who didn’t take part in the study but is familiar with its findings, said in an interview that the study is a “well-done analysis.”

The findings are not surprising, he said. “The overall risk of stroke recurrence was 4.3% at 1 year while the mortality rate was higher at 15.4%. Given that the median CHA₂DS₂-VASc score was 4 and the average age was 79, the stroke recurrence rate and mortality rate are in line with prior studies.”

In regard to the power of OAC therapy to prevent recurrent strokes, Dr. Messe noted that patients may not be adhering to prescribed regimens. Also, “while DOACs are clearly safer that vitamin K–dependent anticoagulants, the medications are generally not dose adjusted. It is possible that adjusting the dose based on measured anti-Xa levels to insure therapeutic anticoagulant effects may reduce the stroke risk further.”

He added that “most of these patients with prior stroke and atrial fibrillation are vasculopathic and at risk of additional strokes due to other mechanisms such as small vessel or large vessel disease.”

In the big picture, the study “confirms again that anticoagulation should be prescribed to all patients with atrial fibrillation and prior stroke, unless there is a strong bleeding risk contraindication,” Dr. Messe said. These patients are clearly at high risk of stroke recurrence and mortality, and all risk factors should be aggressively managed.”

Researchers are exploring other options, he said. “For example, there are studies of factor XI inhibitors that could be added to a DOAC for additional reductions in ischemic stroke. In addition, in patients undergoing cardiac surgery, the randomized trial LAOS III demonstrated that surgical left atrial occlusion in addition to anticoagulation may provide additional stroke prevention.”

Dr. Gaist disclosed personal fees from Pfizer and Bristol Myers Squibb, and grants from Bayer. Several other authors reported various relationships with industry. Dr. Messe has no disclosures.
 

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Bothersome urinary symptoms and incontinence at 12 months post partum are common and treatable, so screening for those symptoms as well as associated depression and anxiety is essential, write authors of a new study.

Sonia Bhandari Randhawa, MD, with the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center in Dallas, led the study published in Urogynecology, which identified factors associated with persistent stress urinary incontinence (SUI), marked by leakage from sudden movements such as coughing or jumping; urgency UI (UUI), leakage after a sudden and intense need to urinate, even if the bladder isn’t full; and other overall bothersome urinary symptoms 1 year after delivery.
 

Associations by Subtype

Dr. Randhawa analyzed data provided by 419 patients (77% Hispanic White and 22% non-Hispanic Black). After multivariable analysis, SUI (n = 136, 32.5%) was significantly associated with greater body mass index (BMI) at the time of delivery and greater depression screening scores. Factors not associated included fetal birth weight, mode of delivery, degree of laceration, and breastfeeding status.

UUI (n = 69, 16.5%) was significantly associated with more births and higher anxiety screening scores. Women with overall urinary symptom bother also had significantly more births and higher anxiety screening scores.

“These findings support the [American College of Obstetricians and Gynecologists] recommendations for routine mental health and urinary incontinence screening in the postpartum period,” said Gena Dunivan, MD, director of the Division of Urogynecology and Pelvic Reconstructive Surgery at University of Alabama–Birmingham, who was not part of the study. “Routine screening for these issues will hopefully reduce the stigma, allowing more patients to receive the help they deserve.”
 

1 in 3 Postpartum Patients Affected by Urinary Incontinence

About one third of postpartum patients are affected by urinary incontinence, which is linked with poorer quality of life and mental health outcomes, the authors note.

Estimates of incontinence frequency post partum vary depending on the population studied, differences in subgroups, and definition of urinary incontinence. A strength of the study was its sizable population, made up almost entirely of Hispanic White and non-Hispanic Black women receiving care at a large safety-net hospital.

“This study has important clinical implications for postpartum patients,” the authors write. “Given an array of proven treatment options for both UUI and SUI, maternal health surveillance needs to include routine inquiry about UI to overcome patients’ reluctance for seeking care. Next, as elevated BMI was identified as a risk factor for persistent postpartum SUI, maintaining a healthy weight should be routinely encouraged during antenatal and postpartum clinic visits.”

Lauren Giugale, MD, director of UPMC’s Magee-Womens Hospital Postpartum Pelvic Floor Healing Clinic in Pittsburgh, Pennsylvania, says an important aspect of the study is that it measured urinary symptoms 1 year after delivery and shows that these symptoms persist. “A lot of studies look more short term,” she noted.

She also pointed to the study’s population of Black and Hispanic women, populations which “have been pretty hard to capture in urogynecology research. It’s important for us to understand these urinary symptoms are affecting those women as well as White women.”
 

Association With Anxiety

The association between postpartum depression scores and SUI is important, she says, but Dr. Randhawa’s team also “uniquely looked at anxiety scores in postpartum women. They showed an association between anxiety scores and UUI, so there’s certainly a potential impact of postpartum urinary symptoms on maternal mental health and maternal well-being.” The relationship between anxiety and depression and postpartum urinary symptoms is not well understood and warrants further research, she says.

In her role, Dr. Giugale says, she always asks about urinary symptoms, particularly in postpartum women. But she notes that some ob.gyn.s without urogynecology training may not prioritize those questions amid all the other information they need to cover.

She says she tells her residents to ask patients pointedly, “Are you having any urine leakage? Patients may not think it’s a problem that can be addressed. We do patients a disservice when we don’t ask the important questions that might potentially impact patients’ lives.”

The authors and Dr. Giugale and Dr. Dunivan report no relevant financial relationships.

Bothersome urinary symptoms and incontinence at 12 months post partum are common and treatable, so screening for those symptoms as well as associated depression and anxiety is essential, write authors of a new study.

Sonia Bhandari Randhawa, MD, with the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center in Dallas, led the study published in Urogynecology, which identified factors associated with persistent stress urinary incontinence (SUI), marked by leakage from sudden movements such as coughing or jumping; urgency UI (UUI), leakage after a sudden and intense need to urinate, even if the bladder isn’t full; and other overall bothersome urinary symptoms 1 year after delivery.
 

Associations by Subtype

Dr. Randhawa analyzed data provided by 419 patients (77% Hispanic White and 22% non-Hispanic Black). After multivariable analysis, SUI (n = 136, 32.5%) was significantly associated with greater body mass index (BMI) at the time of delivery and greater depression screening scores. Factors not associated included fetal birth weight, mode of delivery, degree of laceration, and breastfeeding status.

UUI (n = 69, 16.5%) was significantly associated with more births and higher anxiety screening scores. Women with overall urinary symptom bother also had significantly more births and higher anxiety screening scores.

“These findings support the [American College of Obstetricians and Gynecologists] recommendations for routine mental health and urinary incontinence screening in the postpartum period,” said Gena Dunivan, MD, director of the Division of Urogynecology and Pelvic Reconstructive Surgery at University of Alabama–Birmingham, who was not part of the study. “Routine screening for these issues will hopefully reduce the stigma, allowing more patients to receive the help they deserve.”
 

1 in 3 Postpartum Patients Affected by Urinary Incontinence

About one third of postpartum patients are affected by urinary incontinence, which is linked with poorer quality of life and mental health outcomes, the authors note.

Estimates of incontinence frequency post partum vary depending on the population studied, differences in subgroups, and definition of urinary incontinence. A strength of the study was its sizable population, made up almost entirely of Hispanic White and non-Hispanic Black women receiving care at a large safety-net hospital.

“This study has important clinical implications for postpartum patients,” the authors write. “Given an array of proven treatment options for both UUI and SUI, maternal health surveillance needs to include routine inquiry about UI to overcome patients’ reluctance for seeking care. Next, as elevated BMI was identified as a risk factor for persistent postpartum SUI, maintaining a healthy weight should be routinely encouraged during antenatal and postpartum clinic visits.”

Lauren Giugale, MD, director of UPMC’s Magee-Womens Hospital Postpartum Pelvic Floor Healing Clinic in Pittsburgh, Pennsylvania, says an important aspect of the study is that it measured urinary symptoms 1 year after delivery and shows that these symptoms persist. “A lot of studies look more short term,” she noted.

She also pointed to the study’s population of Black and Hispanic women, populations which “have been pretty hard to capture in urogynecology research. It’s important for us to understand these urinary symptoms are affecting those women as well as White women.”
 

Association With Anxiety

The association between postpartum depression scores and SUI is important, she says, but Dr. Randhawa’s team also “uniquely looked at anxiety scores in postpartum women. They showed an association between anxiety scores and UUI, so there’s certainly a potential impact of postpartum urinary symptoms on maternal mental health and maternal well-being.” The relationship between anxiety and depression and postpartum urinary symptoms is not well understood and warrants further research, she says.

In her role, Dr. Giugale says, she always asks about urinary symptoms, particularly in postpartum women. But she notes that some ob.gyn.s without urogynecology training may not prioritize those questions amid all the other information they need to cover.

She says she tells her residents to ask patients pointedly, “Are you having any urine leakage? Patients may not think it’s a problem that can be addressed. We do patients a disservice when we don’t ask the important questions that might potentially impact patients’ lives.”

The authors and Dr. Giugale and Dr. Dunivan report no relevant financial relationships.

Bothersome urinary symptoms and incontinence at 12 months post partum are common and treatable, so screening for those symptoms as well as associated depression and anxiety is essential, write authors of a new study.

Sonia Bhandari Randhawa, MD, with the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center in Dallas, led the study published in Urogynecology, which identified factors associated with persistent stress urinary incontinence (SUI), marked by leakage from sudden movements such as coughing or jumping; urgency UI (UUI), leakage after a sudden and intense need to urinate, even if the bladder isn’t full; and other overall bothersome urinary symptoms 1 year after delivery.
 

Associations by Subtype

Dr. Randhawa analyzed data provided by 419 patients (77% Hispanic White and 22% non-Hispanic Black). After multivariable analysis, SUI (n = 136, 32.5%) was significantly associated with greater body mass index (BMI) at the time of delivery and greater depression screening scores. Factors not associated included fetal birth weight, mode of delivery, degree of laceration, and breastfeeding status.

UUI (n = 69, 16.5%) was significantly associated with more births and higher anxiety screening scores. Women with overall urinary symptom bother also had significantly more births and higher anxiety screening scores.

“These findings support the [American College of Obstetricians and Gynecologists] recommendations for routine mental health and urinary incontinence screening in the postpartum period,” said Gena Dunivan, MD, director of the Division of Urogynecology and Pelvic Reconstructive Surgery at University of Alabama–Birmingham, who was not part of the study. “Routine screening for these issues will hopefully reduce the stigma, allowing more patients to receive the help they deserve.”
 

1 in 3 Postpartum Patients Affected by Urinary Incontinence

About one third of postpartum patients are affected by urinary incontinence, which is linked with poorer quality of life and mental health outcomes, the authors note.

Estimates of incontinence frequency post partum vary depending on the population studied, differences in subgroups, and definition of urinary incontinence. A strength of the study was its sizable population, made up almost entirely of Hispanic White and non-Hispanic Black women receiving care at a large safety-net hospital.

“This study has important clinical implications for postpartum patients,” the authors write. “Given an array of proven treatment options for both UUI and SUI, maternal health surveillance needs to include routine inquiry about UI to overcome patients’ reluctance for seeking care. Next, as elevated BMI was identified as a risk factor for persistent postpartum SUI, maintaining a healthy weight should be routinely encouraged during antenatal and postpartum clinic visits.”

Lauren Giugale, MD, director of UPMC’s Magee-Womens Hospital Postpartum Pelvic Floor Healing Clinic in Pittsburgh, Pennsylvania, says an important aspect of the study is that it measured urinary symptoms 1 year after delivery and shows that these symptoms persist. “A lot of studies look more short term,” she noted.

She also pointed to the study’s population of Black and Hispanic women, populations which “have been pretty hard to capture in urogynecology research. It’s important for us to understand these urinary symptoms are affecting those women as well as White women.”
 

Association With Anxiety

The association between postpartum depression scores and SUI is important, she says, but Dr. Randhawa’s team also “uniquely looked at anxiety scores in postpartum women. They showed an association between anxiety scores and UUI, so there’s certainly a potential impact of postpartum urinary symptoms on maternal mental health and maternal well-being.” The relationship between anxiety and depression and postpartum urinary symptoms is not well understood and warrants further research, she says.

In her role, Dr. Giugale says, she always asks about urinary symptoms, particularly in postpartum women. But she notes that some ob.gyn.s without urogynecology training may not prioritize those questions amid all the other information they need to cover.

She says she tells her residents to ask patients pointedly, “Are you having any urine leakage? Patients may not think it’s a problem that can be addressed. We do patients a disservice when we don’t ask the important questions that might potentially impact patients’ lives.”

The authors and Dr. Giugale and Dr. Dunivan report no relevant financial relationships.

Should a patient with high lipoprotein (a), or Lp(a), be started on low-dose aspirin?

This is the conundrum facing many physicians and patients, but even getting to that point will require more availability and coverage of tests and a greater appreciation of the risk associated with Lp(a), said cardiologists.
 

Lp(a): The Silent Risk

On Lp(a) Awareness Day, C. Michael Gibson, MD, MA, CEO of the Baim Institute for Clinical Research, Boston, Massachusetts, and PERFUSE took the opportunity to talk about his experiences with testing on X.

The professor of medicine at Harvard Medical School, also in Boston, said he was surprised to find that he had a very high calcium score, despite a low-density lipoprotein (LDL) cholesterol level of just 70 mg/dL. Eventually, he found out that he had a “very, very high Lp(a),” which was particularly concerning because his grandfather died of a heart attack at 45 years of age.

But how much risk does that represent?

A 2022 consensus statement from the European Atherosclerosis Society (EAS) highlighted that epidemiologic and genetic studies “strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes,” even at very low LDL cholesterol levels.

This is because Lp(a) has proinflammatory and proatherosclerotic properties, and high levels are associated with both micro- and macrocalcification of the aortic valve. Findings from a US registry study also suggest the threshold related to increased cardiovascular risk may differ for primary and secondary prevention populations (J Am Coll Cardiol. 2024 Mar 5;83[9]:873-886).

Lp(a) is, however, genetically determined, and there are no drugs available that directly lower levels, although some are on the horizon. In the meantime, the experts behind the consensus statement recommend that all adults be tested at least once in their lifetime.
 

Testing Cost and Availability

This recommendation has been translated into guidelines in “many, many” countries, said lead author Florian Kronenberg, MD, MAE, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria, but “we are far away from reaching that goal.”

“We’ve got a real problem,” added Stephen Nicholls, MD, PhD, director of the Victorian Heart Institute and a professor of cardiology at Monash University, Melbourne, Australia, as there is “not a country in the world where there’s good access to Lp(a) testing.”

Dr. Kronenberg said that the consensus statement “created a kind of momentum” toward universal testing.

Ulrich Laufs, MD, PhD, professor and chair, Department of Cardiology, University Hospital Leipzig, Leipzig, Germany, agreed, saying that, overall, Lp(a) testing has “increased dramatically,” albeit from “extremely low levels.”

Dr. Kronenberg believes that “we have to be really patient.” He cited a lack of knowledge among physicians as one of the biggest barriers to greater uptake of testing.

“There is still no appreciation of the role of Lp(a),” agreed Alberico L. Catapano, MD, PhD, director of Cardiovascular Research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, Italy, and past president of the EAS.

“That’s why it’s not mentioned” to patients, he said. “What is really needed is to inform physician colleagues that Lp(a) is not only a risk factor but is the cause” of atherosclerotic cardiovascular disease (ASCVD).

Dr. Kronenberg said that the pressure for testing can often come from the patient themselves.

Physicians then question why the patient wants to be tested when there are no medications to treat it, he added. “We really tried very hard when we did the consensus paper to say that we should perform the test and give people advice on what to do.”

Dr. Catapano believes that another major obstacle is the cost of the test, which remains high “because very few people do it,” and there is some debate over which test to use.

Taken together, these issues have meant that “payers are really struggling with the idea of funding Lp(a),” said Dr. Nicholls, adding that “there seems to be this fixation on: ‘Well, if you can’t lower Lp(a), why measure it?’ ”

Rather than blame the payers, he says there is a need to educate about the science behind testing and underline that Lp(a) is an “important risk enhancer” for cardiovascular disease.

“Because if we’re going to make people pay out of pocket, then you’re creating a massive equity issue in that only those who can afford the test have it.”
 

High Lp(a) Now What?

But once the test has been performed, there then comes the question as to what to do about the result.

“Before we get anywhere near an agent that effectively lowers Lp(a) and get it into the clinic, there are lots of things that we can do today,” said Dr. Nicholls.

If someone has an intermediate or high background cardiovascular risk and they have got a high Lp(a) level, they “should be treated more intensively, as we know that high Lp(a) patients do better if their LDL cholesterol and their blood pressure is lower.”

For Dr. Catapano, this means having the “same mindset as you do with [a patient with] high blood pressure, high LDL cholesterol, and so on, because it’s exactly the same thing: It’s interacting with your other risk factors to increase your overall risk.”

Dr. Gibson agreed. Through a range of measures, including weight loss and statin therapy, he was able to reduce his overall cardiovascular risk, and his LDL cholesterol level dropped to just 20 mg/dL.
 

A Role for Aspirin?

However, one debate that has been rolling on in recent months is whether to start patients with elevated Lp(a) on low-dose aspirin.

It gained added momentum when Pablo Corral, MD, a lipidologist and a professor in the School of Medicine, Pharmacology Department, FASTA University, Mar del Plata, Buenos Aires, Argentina, highlighted the issue on X.

He pointed to a recent study, which showed that regular aspirin use was associated with a significantly lower rate of ASCVD mortality in adults without clinical ASCVD but who had elevated Lp(a).

Dr. Nicholls said that, when you “peel away the layers” of the current evidence, there is some suggestion that Lp(a)may be prothrombotic. “So in theory, perhaps aspirin might be maybe more intuitively useful there.”

He noted that the ASPREE primary prevention study found that low-dose aspirin in older adults resulted in a significantly higher risk for major hemorrhage over placebo and did not significantly reduce the risk for cardiovascular disease.

But an analysis he and his colleagues did suggest that aspirin may indeed benefit older individuals if they have elevated Lp(a) genotypes.
 

An Individual Decision

For Dr. Kronenberg and Dr. Laufs, there is currently a lack of appropriate data to make a recommendation either way, particularly for primary prevention.

They warned that the risk for thrombosis in patients with mildly elevated Lp(a) cannot be discounted, and in most cases either “the existing risk of bleeding exceeds the beneficial effects [of aspirin], or it’s not indicated,” said Dr. Laufs.

“When we make a recommendation, we should have evidence-based data,” Dr. Kronenberg said, but, at the moment, people “somehow put their finger in the air and see” which way the wind is blowing.

Dr. Catapano urged patients to talk to their physician, as even low-dose aspirin is “very potent” at inhibiting platelets.

Dr. Gibson agreed, saying that he is in two minds, as the potential benefit has to be weighed against the bleeding risk.

He personally takes low-dose aspirin because “I know I have a low bleeding risk,” but it is a decision “that has to be taken individually between a patient and their physician.”

Dr. Gibson, Dr. Kronenberg, Dr. Nicholls, and Dr. Catapano all reported conflicts of interest with numerous pharmaceutical companies and organizations.

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

Should a patient with high lipoprotein (a), or Lp(a), be started on low-dose aspirin?

This is the conundrum facing many physicians and patients, but even getting to that point will require more availability and coverage of tests and a greater appreciation of the risk associated with Lp(a), said cardiologists.
 

Lp(a): The Silent Risk

On Lp(a) Awareness Day, C. Michael Gibson, MD, MA, CEO of the Baim Institute for Clinical Research, Boston, Massachusetts, and PERFUSE took the opportunity to talk about his experiences with testing on X.

The professor of medicine at Harvard Medical School, also in Boston, said he was surprised to find that he had a very high calcium score, despite a low-density lipoprotein (LDL) cholesterol level of just 70 mg/dL. Eventually, he found out that he had a “very, very high Lp(a),” which was particularly concerning because his grandfather died of a heart attack at 45 years of age.

But how much risk does that represent?

A 2022 consensus statement from the European Atherosclerosis Society (EAS) highlighted that epidemiologic and genetic studies “strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes,” even at very low LDL cholesterol levels.

This is because Lp(a) has proinflammatory and proatherosclerotic properties, and high levels are associated with both micro- and macrocalcification of the aortic valve. Findings from a US registry study also suggest the threshold related to increased cardiovascular risk may differ for primary and secondary prevention populations (J Am Coll Cardiol. 2024 Mar 5;83[9]:873-886).

Lp(a) is, however, genetically determined, and there are no drugs available that directly lower levels, although some are on the horizon. In the meantime, the experts behind the consensus statement recommend that all adults be tested at least once in their lifetime.
 

Testing Cost and Availability

This recommendation has been translated into guidelines in “many, many” countries, said lead author Florian Kronenberg, MD, MAE, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria, but “we are far away from reaching that goal.”

“We’ve got a real problem,” added Stephen Nicholls, MD, PhD, director of the Victorian Heart Institute and a professor of cardiology at Monash University, Melbourne, Australia, as there is “not a country in the world where there’s good access to Lp(a) testing.”

Dr. Kronenberg said that the consensus statement “created a kind of momentum” toward universal testing.

Ulrich Laufs, MD, PhD, professor and chair, Department of Cardiology, University Hospital Leipzig, Leipzig, Germany, agreed, saying that, overall, Lp(a) testing has “increased dramatically,” albeit from “extremely low levels.”

Dr. Kronenberg believes that “we have to be really patient.” He cited a lack of knowledge among physicians as one of the biggest barriers to greater uptake of testing.

“There is still no appreciation of the role of Lp(a),” agreed Alberico L. Catapano, MD, PhD, director of Cardiovascular Research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, Italy, and past president of the EAS.

“That’s why it’s not mentioned” to patients, he said. “What is really needed is to inform physician colleagues that Lp(a) is not only a risk factor but is the cause” of atherosclerotic cardiovascular disease (ASCVD).

Dr. Kronenberg said that the pressure for testing can often come from the patient themselves.

Physicians then question why the patient wants to be tested when there are no medications to treat it, he added. “We really tried very hard when we did the consensus paper to say that we should perform the test and give people advice on what to do.”

Dr. Catapano believes that another major obstacle is the cost of the test, which remains high “because very few people do it,” and there is some debate over which test to use.

Taken together, these issues have meant that “payers are really struggling with the idea of funding Lp(a),” said Dr. Nicholls, adding that “there seems to be this fixation on: ‘Well, if you can’t lower Lp(a), why measure it?’ ”

Rather than blame the payers, he says there is a need to educate about the science behind testing and underline that Lp(a) is an “important risk enhancer” for cardiovascular disease.

“Because if we’re going to make people pay out of pocket, then you’re creating a massive equity issue in that only those who can afford the test have it.”
 

High Lp(a) Now What?

But once the test has been performed, there then comes the question as to what to do about the result.

“Before we get anywhere near an agent that effectively lowers Lp(a) and get it into the clinic, there are lots of things that we can do today,” said Dr. Nicholls.

If someone has an intermediate or high background cardiovascular risk and they have got a high Lp(a) level, they “should be treated more intensively, as we know that high Lp(a) patients do better if their LDL cholesterol and their blood pressure is lower.”

For Dr. Catapano, this means having the “same mindset as you do with [a patient with] high blood pressure, high LDL cholesterol, and so on, because it’s exactly the same thing: It’s interacting with your other risk factors to increase your overall risk.”

Dr. Gibson agreed. Through a range of measures, including weight loss and statin therapy, he was able to reduce his overall cardiovascular risk, and his LDL cholesterol level dropped to just 20 mg/dL.
 

A Role for Aspirin?

However, one debate that has been rolling on in recent months is whether to start patients with elevated Lp(a) on low-dose aspirin.

It gained added momentum when Pablo Corral, MD, a lipidologist and a professor in the School of Medicine, Pharmacology Department, FASTA University, Mar del Plata, Buenos Aires, Argentina, highlighted the issue on X.

He pointed to a recent study, which showed that regular aspirin use was associated with a significantly lower rate of ASCVD mortality in adults without clinical ASCVD but who had elevated Lp(a).

Dr. Nicholls said that, when you “peel away the layers” of the current evidence, there is some suggestion that Lp(a)may be prothrombotic. “So in theory, perhaps aspirin might be maybe more intuitively useful there.”

He noted that the ASPREE primary prevention study found that low-dose aspirin in older adults resulted in a significantly higher risk for major hemorrhage over placebo and did not significantly reduce the risk for cardiovascular disease.

But an analysis he and his colleagues did suggest that aspirin may indeed benefit older individuals if they have elevated Lp(a) genotypes.
 

An Individual Decision

For Dr. Kronenberg and Dr. Laufs, there is currently a lack of appropriate data to make a recommendation either way, particularly for primary prevention.

They warned that the risk for thrombosis in patients with mildly elevated Lp(a) cannot be discounted, and in most cases either “the existing risk of bleeding exceeds the beneficial effects [of aspirin], or it’s not indicated,” said Dr. Laufs.

“When we make a recommendation, we should have evidence-based data,” Dr. Kronenberg said, but, at the moment, people “somehow put their finger in the air and see” which way the wind is blowing.

Dr. Catapano urged patients to talk to their physician, as even low-dose aspirin is “very potent” at inhibiting platelets.

Dr. Gibson agreed, saying that he is in two minds, as the potential benefit has to be weighed against the bleeding risk.

He personally takes low-dose aspirin because “I know I have a low bleeding risk,” but it is a decision “that has to be taken individually between a patient and their physician.”

Dr. Gibson, Dr. Kronenberg, Dr. Nicholls, and Dr. Catapano all reported conflicts of interest with numerous pharmaceutical companies and organizations.

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

Should a patient with high lipoprotein (a), or Lp(a), be started on low-dose aspirin?

This is the conundrum facing many physicians and patients, but even getting to that point will require more availability and coverage of tests and a greater appreciation of the risk associated with Lp(a), said cardiologists.
 

Lp(a): The Silent Risk

On Lp(a) Awareness Day, C. Michael Gibson, MD, MA, CEO of the Baim Institute for Clinical Research, Boston, Massachusetts, and PERFUSE took the opportunity to talk about his experiences with testing on X.

The professor of medicine at Harvard Medical School, also in Boston, said he was surprised to find that he had a very high calcium score, despite a low-density lipoprotein (LDL) cholesterol level of just 70 mg/dL. Eventually, he found out that he had a “very, very high Lp(a),” which was particularly concerning because his grandfather died of a heart attack at 45 years of age.

But how much risk does that represent?

A 2022 consensus statement from the European Atherosclerosis Society (EAS) highlighted that epidemiologic and genetic studies “strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes,” even at very low LDL cholesterol levels.

This is because Lp(a) has proinflammatory and proatherosclerotic properties, and high levels are associated with both micro- and macrocalcification of the aortic valve. Findings from a US registry study also suggest the threshold related to increased cardiovascular risk may differ for primary and secondary prevention populations (J Am Coll Cardiol. 2024 Mar 5;83[9]:873-886).

Lp(a) is, however, genetically determined, and there are no drugs available that directly lower levels, although some are on the horizon. In the meantime, the experts behind the consensus statement recommend that all adults be tested at least once in their lifetime.
 

Testing Cost and Availability

This recommendation has been translated into guidelines in “many, many” countries, said lead author Florian Kronenberg, MD, MAE, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria, but “we are far away from reaching that goal.”

“We’ve got a real problem,” added Stephen Nicholls, MD, PhD, director of the Victorian Heart Institute and a professor of cardiology at Monash University, Melbourne, Australia, as there is “not a country in the world where there’s good access to Lp(a) testing.”

Dr. Kronenberg said that the consensus statement “created a kind of momentum” toward universal testing.

Ulrich Laufs, MD, PhD, professor and chair, Department of Cardiology, University Hospital Leipzig, Leipzig, Germany, agreed, saying that, overall, Lp(a) testing has “increased dramatically,” albeit from “extremely low levels.”

Dr. Kronenberg believes that “we have to be really patient.” He cited a lack of knowledge among physicians as one of the biggest barriers to greater uptake of testing.

“There is still no appreciation of the role of Lp(a),” agreed Alberico L. Catapano, MD, PhD, director of Cardiovascular Research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, Italy, and past president of the EAS.

“That’s why it’s not mentioned” to patients, he said. “What is really needed is to inform physician colleagues that Lp(a) is not only a risk factor but is the cause” of atherosclerotic cardiovascular disease (ASCVD).

Dr. Kronenberg said that the pressure for testing can often come from the patient themselves.

Physicians then question why the patient wants to be tested when there are no medications to treat it, he added. “We really tried very hard when we did the consensus paper to say that we should perform the test and give people advice on what to do.”

Dr. Catapano believes that another major obstacle is the cost of the test, which remains high “because very few people do it,” and there is some debate over which test to use.

Taken together, these issues have meant that “payers are really struggling with the idea of funding Lp(a),” said Dr. Nicholls, adding that “there seems to be this fixation on: ‘Well, if you can’t lower Lp(a), why measure it?’ ”

Rather than blame the payers, he says there is a need to educate about the science behind testing and underline that Lp(a) is an “important risk enhancer” for cardiovascular disease.

“Because if we’re going to make people pay out of pocket, then you’re creating a massive equity issue in that only those who can afford the test have it.”
 

High Lp(a) Now What?

But once the test has been performed, there then comes the question as to what to do about the result.

“Before we get anywhere near an agent that effectively lowers Lp(a) and get it into the clinic, there are lots of things that we can do today,” said Dr. Nicholls.

If someone has an intermediate or high background cardiovascular risk and they have got a high Lp(a) level, they “should be treated more intensively, as we know that high Lp(a) patients do better if their LDL cholesterol and their blood pressure is lower.”

For Dr. Catapano, this means having the “same mindset as you do with [a patient with] high blood pressure, high LDL cholesterol, and so on, because it’s exactly the same thing: It’s interacting with your other risk factors to increase your overall risk.”

Dr. Gibson agreed. Through a range of measures, including weight loss and statin therapy, he was able to reduce his overall cardiovascular risk, and his LDL cholesterol level dropped to just 20 mg/dL.
 

A Role for Aspirin?

However, one debate that has been rolling on in recent months is whether to start patients with elevated Lp(a) on low-dose aspirin.

It gained added momentum when Pablo Corral, MD, a lipidologist and a professor in the School of Medicine, Pharmacology Department, FASTA University, Mar del Plata, Buenos Aires, Argentina, highlighted the issue on X.

He pointed to a recent study, which showed that regular aspirin use was associated with a significantly lower rate of ASCVD mortality in adults without clinical ASCVD but who had elevated Lp(a).

Dr. Nicholls said that, when you “peel away the layers” of the current evidence, there is some suggestion that Lp(a)may be prothrombotic. “So in theory, perhaps aspirin might be maybe more intuitively useful there.”

He noted that the ASPREE primary prevention study found that low-dose aspirin in older adults resulted in a significantly higher risk for major hemorrhage over placebo and did not significantly reduce the risk for cardiovascular disease.

But an analysis he and his colleagues did suggest that aspirin may indeed benefit older individuals if they have elevated Lp(a) genotypes.
 

An Individual Decision

For Dr. Kronenberg and Dr. Laufs, there is currently a lack of appropriate data to make a recommendation either way, particularly for primary prevention.

They warned that the risk for thrombosis in patients with mildly elevated Lp(a) cannot be discounted, and in most cases either “the existing risk of bleeding exceeds the beneficial effects [of aspirin], or it’s not indicated,” said Dr. Laufs.

“When we make a recommendation, we should have evidence-based data,” Dr. Kronenberg said, but, at the moment, people “somehow put their finger in the air and see” which way the wind is blowing.

Dr. Catapano urged patients to talk to their physician, as even low-dose aspirin is “very potent” at inhibiting platelets.

Dr. Gibson agreed, saying that he is in two minds, as the potential benefit has to be weighed against the bleeding risk.

He personally takes low-dose aspirin because “I know I have a low bleeding risk,” but it is a decision “that has to be taken individually between a patient and their physician.”

Dr. Gibson, Dr. Kronenberg, Dr. Nicholls, and Dr. Catapano all reported conflicts of interest with numerous pharmaceutical companies and organizations.

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

ORLANDO, Florida — Clinicians should keep in mind concerns about overdiagnosis of thyroid cancer when prescribing glucagon-like peptide 1 (GLP-1) drugs, as the US boxed warning about this risk for this class of medicines for certain tumors in mice could trigger excess screening, an expert endocrinologist said.

Speaking at the annual American Diabetes Association (ADA) 84th Scientific Sessions, Elizabeth N. Pearce, MD, MSc, a professor of medicine at Boston University, Boston, reviewed the different approaches US and European regulators have taken for the GLP-1 drugs. She also explained the current concerns about the wide use of thyroid screening in general and how these intersect with the rapid uptake of the GLP-1 drugs.

“We should not be screening for thyroid nodules before or during GLP-1 receptor agonist treatment just because the patients are on these medications,” said Dr. Pearce, who is also a former board president of the American Thyroid Association (ATA). “We do not want to contribute to this epidemic of overdiagnosis of thyroid cancer.”

The ATA and the US Preventive Services Task Force (USPSTF) are among the health organizations that have in recent years sought to boost public awareness of the potential risks for excess screening of thyroid nodules. In 2017, the USPSTF, which influences insurance coverage, recommended against routine screening for thyroid cancer in asymptomatic adults. At that time, the incidence of thyroid cancer detection had increased by 4.5% per year over a decade, faster than for any other cancer, but without a corresponding change in the mortality rate, USPSTF said.

“Unequivocally, the thyroid cancer mortality has not kept pace with thyroid cancer detection,” Dr. Pearce said at the ADA meeting. “We’ve been diagnosing a lot of small thyroid cancers that people would otherwise have been destined to die with and not die of.”

Dr. Pearce said clinicians should be careful not to overly restrict access to GLP-1 drugs due to concerns about thyroid cancer — and they should use care in screening nodules.

It’s possible that the weight loss experienced by people taking GLP-1 drugs may make preexisting thyroid nodules more prominent, Dr. Pearce said. It’s also likely that the US boxed warning on thyroid risk on GLP-1 drugs makes clinicians and patients more likely to look for these kinds of growths.

Dr. Pearce urged adherence to guidelines such as the ones the ATA published in 2015 for assessing nodules.

In an interview with this news organization, Dr. Pearce noted the frequency of CT scans in US medical practice in turning up many incidental thyroid nodules, a finding that can cause some panic for patients and their clinicians.

But it helps to put these findings in context, as by the age of 50, about 40% of women will have at least one thyroid nodule, making this a very common finding, she said.

“The vast majority are not malignant,” Dr. Pearce said. “When you explain this to patients, it alleviates anxiety.”
 

The US, European Union Differences

In the United States, the label for GLP-1 drugs starts with a boxed warning about thyroid C-cell tumors seen in rodents given these medicines in testing.

It’s unknown if the medicines could cause medullary thyroid carcinoma (MTC) in humans, the label adds. The drug is contraindicated in patients with a personal or family history of MTC or multiple endocrine neoplasia syndrome 2, the boxed warning says. This is based largely on data seen in laboratory rats.

“It’s a big black box warning that gets people’s attention,” Dr. Pearce said. “Important to note that if you practice in Europe, you will not be familiar with this labeling because it doesn’t exist there. They’ve never had this warning on the European package.”

The European Medicines Agency (EMA) does include information about the results of rodent studies as part of the discussion of known and potential risks for GLP-1 drugs but has not emphasized it in the same way as the US drug labels do.

For example, the public assessment report posted on the EMA website for semaglutide (Ozempic, Novo Nordisk) notes that nonlethal thyroid C-cell tumors “observed in rodents are a class effect for GLP-1 receptor agonists.” It’s possible that these may be due to a particular sensitivity in rodents, the report said.

“The relevance for humans is considered to be low but cannot be completely excluded,” the EMA report said in the product information section of the report.

There has been ongoing interest in the issue.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) in October concluded that the available evidence does not support a causal association between GLP-1 receptor agonists and thyroid cancer.

The EMA’s PRAC safety committee said it began assessing the evidence about a possible connection following the publication of a study in 2022 in the journal Diabetes Care. That paper reported on an analysis that suggested increased risk for all thyroid cancer and medullary thyroid cancer with the use of GLP-1 drugs, particularly after 1-3 years of treatment.

The EMA’s PRAC said that in making its decision, it also considered other published papers on this topic as well as clinical and postmarketing data on GLP-1 drugs.

In an email interview, Jean-Luc Faillie, MD, PhD, corresponding author of the Diabetes Care paper, called for continued “vigilance and prudence in clinical practice” with GLP-1 drugs.

His paper reported on a case-control analysis on the basis of reports from the French national healthcare insurance system database, looking at people who had taken GLP-1 drugs and similar people who had not.

Due to a lack of a specific diagnostic code for medullary thyroid cancers, the researchers used a composite definition combining thyroid cancer diagnosis with several calcitonin tests, a carcinoembryonic antigen test, or a specific treatment (vandetanib) to identify potential cases of this cancer.

It’s possible that this method could have led to overestimation of MTC among the cases of thyroid cancer, wrote Dr. Faillie, who is a professor at France’s Université de Montpellier, Montpellier, France, and part of its pharmacological vigilance service.

“Nevertheless, it’s crucial to emphasize that any potential overestimation of MTC cases would likely apply equally to both GLP-1 receptor agonist–exposed and unexposed groups,” Dr. Faillie wrote. “Therefore, it should not significantly impact our main findings regarding the suggested increased risk associated with GLP-1 receptor agonist use.”

Dr. Pearce disclosed honoraria for speaking at the Merck China Forum. Dr. Faille and his coauthors reported no conflicts of interest in the publication of their study. Their research was supported by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, grant 2019S015) in the context of a partnership with the Health Product Epidemiology Scientific Interest Group (EPI-PHARE). The study was part of France’s Drugs Systematized Assessment in Real-Life Environment (DRUGS-SAFEr) research program.

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

ORLANDO, Florida — Clinicians should keep in mind concerns about overdiagnosis of thyroid cancer when prescribing glucagon-like peptide 1 (GLP-1) drugs, as the US boxed warning about this risk for this class of medicines for certain tumors in mice could trigger excess screening, an expert endocrinologist said.

Speaking at the annual American Diabetes Association (ADA) 84th Scientific Sessions, Elizabeth N. Pearce, MD, MSc, a professor of medicine at Boston University, Boston, reviewed the different approaches US and European regulators have taken for the GLP-1 drugs. She also explained the current concerns about the wide use of thyroid screening in general and how these intersect with the rapid uptake of the GLP-1 drugs.

“We should not be screening for thyroid nodules before or during GLP-1 receptor agonist treatment just because the patients are on these medications,” said Dr. Pearce, who is also a former board president of the American Thyroid Association (ATA). “We do not want to contribute to this epidemic of overdiagnosis of thyroid cancer.”

The ATA and the US Preventive Services Task Force (USPSTF) are among the health organizations that have in recent years sought to boost public awareness of the potential risks for excess screening of thyroid nodules. In 2017, the USPSTF, which influences insurance coverage, recommended against routine screening for thyroid cancer in asymptomatic adults. At that time, the incidence of thyroid cancer detection had increased by 4.5% per year over a decade, faster than for any other cancer, but without a corresponding change in the mortality rate, USPSTF said.

“Unequivocally, the thyroid cancer mortality has not kept pace with thyroid cancer detection,” Dr. Pearce said at the ADA meeting. “We’ve been diagnosing a lot of small thyroid cancers that people would otherwise have been destined to die with and not die of.”

Dr. Pearce said clinicians should be careful not to overly restrict access to GLP-1 drugs due to concerns about thyroid cancer — and they should use care in screening nodules.

It’s possible that the weight loss experienced by people taking GLP-1 drugs may make preexisting thyroid nodules more prominent, Dr. Pearce said. It’s also likely that the US boxed warning on thyroid risk on GLP-1 drugs makes clinicians and patients more likely to look for these kinds of growths.

Dr. Pearce urged adherence to guidelines such as the ones the ATA published in 2015 for assessing nodules.

In an interview with this news organization, Dr. Pearce noted the frequency of CT scans in US medical practice in turning up many incidental thyroid nodules, a finding that can cause some panic for patients and their clinicians.

But it helps to put these findings in context, as by the age of 50, about 40% of women will have at least one thyroid nodule, making this a very common finding, she said.

“The vast majority are not malignant,” Dr. Pearce said. “When you explain this to patients, it alleviates anxiety.”
 

The US, European Union Differences

In the United States, the label for GLP-1 drugs starts with a boxed warning about thyroid C-cell tumors seen in rodents given these medicines in testing.

It’s unknown if the medicines could cause medullary thyroid carcinoma (MTC) in humans, the label adds. The drug is contraindicated in patients with a personal or family history of MTC or multiple endocrine neoplasia syndrome 2, the boxed warning says. This is based largely on data seen in laboratory rats.

“It’s a big black box warning that gets people’s attention,” Dr. Pearce said. “Important to note that if you practice in Europe, you will not be familiar with this labeling because it doesn’t exist there. They’ve never had this warning on the European package.”

The European Medicines Agency (EMA) does include information about the results of rodent studies as part of the discussion of known and potential risks for GLP-1 drugs but has not emphasized it in the same way as the US drug labels do.

For example, the public assessment report posted on the EMA website for semaglutide (Ozempic, Novo Nordisk) notes that nonlethal thyroid C-cell tumors “observed in rodents are a class effect for GLP-1 receptor agonists.” It’s possible that these may be due to a particular sensitivity in rodents, the report said.

“The relevance for humans is considered to be low but cannot be completely excluded,” the EMA report said in the product information section of the report.

There has been ongoing interest in the issue.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) in October concluded that the available evidence does not support a causal association between GLP-1 receptor agonists and thyroid cancer.

The EMA’s PRAC safety committee said it began assessing the evidence about a possible connection following the publication of a study in 2022 in the journal Diabetes Care. That paper reported on an analysis that suggested increased risk for all thyroid cancer and medullary thyroid cancer with the use of GLP-1 drugs, particularly after 1-3 years of treatment.

The EMA’s PRAC said that in making its decision, it also considered other published papers on this topic as well as clinical and postmarketing data on GLP-1 drugs.

In an email interview, Jean-Luc Faillie, MD, PhD, corresponding author of the Diabetes Care paper, called for continued “vigilance and prudence in clinical practice” with GLP-1 drugs.

His paper reported on a case-control analysis on the basis of reports from the French national healthcare insurance system database, looking at people who had taken GLP-1 drugs and similar people who had not.

Due to a lack of a specific diagnostic code for medullary thyroid cancers, the researchers used a composite definition combining thyroid cancer diagnosis with several calcitonin tests, a carcinoembryonic antigen test, or a specific treatment (vandetanib) to identify potential cases of this cancer.

It’s possible that this method could have led to overestimation of MTC among the cases of thyroid cancer, wrote Dr. Faillie, who is a professor at France’s Université de Montpellier, Montpellier, France, and part of its pharmacological vigilance service.

“Nevertheless, it’s crucial to emphasize that any potential overestimation of MTC cases would likely apply equally to both GLP-1 receptor agonist–exposed and unexposed groups,” Dr. Faillie wrote. “Therefore, it should not significantly impact our main findings regarding the suggested increased risk associated with GLP-1 receptor agonist use.”

Dr. Pearce disclosed honoraria for speaking at the Merck China Forum. Dr. Faille and his coauthors reported no conflicts of interest in the publication of their study. Their research was supported by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, grant 2019S015) in the context of a partnership with the Health Product Epidemiology Scientific Interest Group (EPI-PHARE). The study was part of France’s Drugs Systematized Assessment in Real-Life Environment (DRUGS-SAFEr) research program.

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

ORLANDO, Florida — Clinicians should keep in mind concerns about overdiagnosis of thyroid cancer when prescribing glucagon-like peptide 1 (GLP-1) drugs, as the US boxed warning about this risk for this class of medicines for certain tumors in mice could trigger excess screening, an expert endocrinologist said.

Speaking at the annual American Diabetes Association (ADA) 84th Scientific Sessions, Elizabeth N. Pearce, MD, MSc, a professor of medicine at Boston University, Boston, reviewed the different approaches US and European regulators have taken for the GLP-1 drugs. She also explained the current concerns about the wide use of thyroid screening in general and how these intersect with the rapid uptake of the GLP-1 drugs.

“We should not be screening for thyroid nodules before or during GLP-1 receptor agonist treatment just because the patients are on these medications,” said Dr. Pearce, who is also a former board president of the American Thyroid Association (ATA). “We do not want to contribute to this epidemic of overdiagnosis of thyroid cancer.”

The ATA and the US Preventive Services Task Force (USPSTF) are among the health organizations that have in recent years sought to boost public awareness of the potential risks for excess screening of thyroid nodules. In 2017, the USPSTF, which influences insurance coverage, recommended against routine screening for thyroid cancer in asymptomatic adults. At that time, the incidence of thyroid cancer detection had increased by 4.5% per year over a decade, faster than for any other cancer, but without a corresponding change in the mortality rate, USPSTF said.

“Unequivocally, the thyroid cancer mortality has not kept pace with thyroid cancer detection,” Dr. Pearce said at the ADA meeting. “We’ve been diagnosing a lot of small thyroid cancers that people would otherwise have been destined to die with and not die of.”

Dr. Pearce said clinicians should be careful not to overly restrict access to GLP-1 drugs due to concerns about thyroid cancer — and they should use care in screening nodules.

It’s possible that the weight loss experienced by people taking GLP-1 drugs may make preexisting thyroid nodules more prominent, Dr. Pearce said. It’s also likely that the US boxed warning on thyroid risk on GLP-1 drugs makes clinicians and patients more likely to look for these kinds of growths.

Dr. Pearce urged adherence to guidelines such as the ones the ATA published in 2015 for assessing nodules.

In an interview with this news organization, Dr. Pearce noted the frequency of CT scans in US medical practice in turning up many incidental thyroid nodules, a finding that can cause some panic for patients and their clinicians.

But it helps to put these findings in context, as by the age of 50, about 40% of women will have at least one thyroid nodule, making this a very common finding, she said.

“The vast majority are not malignant,” Dr. Pearce said. “When you explain this to patients, it alleviates anxiety.”
 

The US, European Union Differences

In the United States, the label for GLP-1 drugs starts with a boxed warning about thyroid C-cell tumors seen in rodents given these medicines in testing.

It’s unknown if the medicines could cause medullary thyroid carcinoma (MTC) in humans, the label adds. The drug is contraindicated in patients with a personal or family history of MTC or multiple endocrine neoplasia syndrome 2, the boxed warning says. This is based largely on data seen in laboratory rats.

“It’s a big black box warning that gets people’s attention,” Dr. Pearce said. “Important to note that if you practice in Europe, you will not be familiar with this labeling because it doesn’t exist there. They’ve never had this warning on the European package.”

The European Medicines Agency (EMA) does include information about the results of rodent studies as part of the discussion of known and potential risks for GLP-1 drugs but has not emphasized it in the same way as the US drug labels do.

For example, the public assessment report posted on the EMA website for semaglutide (Ozempic, Novo Nordisk) notes that nonlethal thyroid C-cell tumors “observed in rodents are a class effect for GLP-1 receptor agonists.” It’s possible that these may be due to a particular sensitivity in rodents, the report said.

“The relevance for humans is considered to be low but cannot be completely excluded,” the EMA report said in the product information section of the report.

There has been ongoing interest in the issue.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) in October concluded that the available evidence does not support a causal association between GLP-1 receptor agonists and thyroid cancer.

The EMA’s PRAC safety committee said it began assessing the evidence about a possible connection following the publication of a study in 2022 in the journal Diabetes Care. That paper reported on an analysis that suggested increased risk for all thyroid cancer and medullary thyroid cancer with the use of GLP-1 drugs, particularly after 1-3 years of treatment.

The EMA’s PRAC said that in making its decision, it also considered other published papers on this topic as well as clinical and postmarketing data on GLP-1 drugs.

In an email interview, Jean-Luc Faillie, MD, PhD, corresponding author of the Diabetes Care paper, called for continued “vigilance and prudence in clinical practice” with GLP-1 drugs.

His paper reported on a case-control analysis on the basis of reports from the French national healthcare insurance system database, looking at people who had taken GLP-1 drugs and similar people who had not.

Due to a lack of a specific diagnostic code for medullary thyroid cancers, the researchers used a composite definition combining thyroid cancer diagnosis with several calcitonin tests, a carcinoembryonic antigen test, or a specific treatment (vandetanib) to identify potential cases of this cancer.

It’s possible that this method could have led to overestimation of MTC among the cases of thyroid cancer, wrote Dr. Faillie, who is a professor at France’s Université de Montpellier, Montpellier, France, and part of its pharmacological vigilance service.

“Nevertheless, it’s crucial to emphasize that any potential overestimation of MTC cases would likely apply equally to both GLP-1 receptor agonist–exposed and unexposed groups,” Dr. Faillie wrote. “Therefore, it should not significantly impact our main findings regarding the suggested increased risk associated with GLP-1 receptor agonist use.”

Dr. Pearce disclosed honoraria for speaking at the Merck China Forum. Dr. Faille and his coauthors reported no conflicts of interest in the publication of their study. Their research was supported by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, grant 2019S015) in the context of a partnership with the Health Product Epidemiology Scientific Interest Group (EPI-PHARE). The study was part of France’s Drugs Systematized Assessment in Real-Life Environment (DRUGS-SAFEr) research program.

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

This transcript has been edited for clarity. 

My oldest daughter is at sleepaway camp for a couple of weeks, and the camp has a photographer who goes around all day taking pictures of the kids, which get uploaded to a private Facebook group. In the past, I would go online every day (or, okay, several times a day) and scroll through all those pictures looking for one that features my kid. 

I don’t have to do that anymore. This year, I simply uploaded a picture of my daughter to an app and artificial intelligence (AI) takes care of the rest, recognizing her face amidst the sea of smiling children, and flagging just those photos for me to peruse. It’s amazing, really. And a bit scary.

The fact that facial recognition has penetrated the summer camp market should tell you that the tech is truly ubiquitous. But today we’re going to think a bit more about what AI can do with a picture of your face, because the power of facial recognition is not just skin deep.

What’s got me hot and bothered about facial images is this paper, appearing in Cell Metabolism, which adds a new layer to the standard facial-analysis playbook: facial temperature.

To understand this paper, you need to understand a whole field of research that is developing various different “clocks” for age. 

It turns out that age really is just a number. Our cells, our proteins, our biochemistry can be analyzed to give different numbers. These “clocks,” as distinct from the calendar we usually use to measure our age, might have more predictive power than the number itself. 

There are numerous molecular clocks, such as telomere length, that not only correlate with calendar age but are superior to calendar age in predicting age-related complications. Testing telomere length typically requires a blood sample — and remains costly. But we can use other sources to estimate age; how about a photo?

I mean, we do this all the time when we meet someone new or, as a physician, when we meet a new patient. I have often written that a patient “appears younger than their stated age,” and we’ve all had the experience of hearing how old someone is and being shocked. I mean, have you seen Sharon Stone recently? She’s 66 years old. Okay — to be fair, there might be some outside help there. But you get the point.

Back to the Cell Metabolism paper. Researchers report on multiple algorithms to obtain an “age” from a picture of an individual’s face. 

The first algorithm is pretty straightforward. Researchers collected 2811 images, all of Han Chinese individuals ranging in age from 20 to 90 years, and reconstructed a 3D facial map from those. 

memubrocheposwowrutaphewrowrimijebrauulathaleswot

prosterechiwremedrijatreclewrivudruwabruluphestespepustostuwruslunusliprukibejifrireshichethupiphemohothastesiwepriseputreualachigovusheruchodrenespestestepebeniphesivuchabrewrajichuphadrililicludrop

phatritribeuacrispicishabrejajuchephebrihedricevoshavivevospitheshuvotretegutrobujawoclodrirekuboswestekiclamacrawrijaveuithejabruvasistebrasicrugonetrowowuuishecropholiclumabristanawreswushislebaphaprihewreshagubreshiclicredrugostubrilegatrid

vatuthoviclobrauucushosudruswudevudrocetujoshoclouibastouetomacafrepreduprehachiwrewiprespirucacleslestisusposholemislunauutrocetetristiclejagewrehisloslecrithewru

thiprapesliposhuphidracloricucluwrispichikilatrehuuubiphadrumuslihouudrupakaprochadidrebijoj

be

swiprabuwroceslidrowruthoshodrulapropithuuucapilechuchoribubrathujireswovifrophuswemaslowruswijajadihogaspabestetrigupreclekushefrowaphowruspupuvatrataspeprolidecuwrowrafratejithucawodisowetinetodreche

br

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

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

This transcript has been edited for clarity. 

My oldest daughter is at sleepaway camp for a couple of weeks, and the camp has a photographer who goes around all day taking pictures of the kids, which get uploaded to a private Facebook group. In the past, I would go online every day (or, okay, several times a day) and scroll through all those pictures looking for one that features my kid. 

I don’t have to do that anymore. This year, I simply uploaded a picture of my daughter to an app and artificial intelligence (AI) takes care of the rest, recognizing her face amidst the sea of smiling children, and flagging just those photos for me to peruse. It’s amazing, really. And a bit scary.

The fact that facial recognition has penetrated the summer camp market should tell you that the tech is truly ubiquitous. But today we’re going to think a bit more about what AI can do with a picture of your face, because the power of facial recognition is not just skin deep.

What’s got me hot and bothered about facial images is this paper, appearing in Cell Metabolism, which adds a new layer to the standard facial-analysis playbook: facial temperature.

To understand this paper, you need to understand a whole field of research that is developing various different “clocks” for age. 

It turns out that age really is just a number. Our cells, our proteins, our biochemistry can be analyzed to give different numbers. These “clocks,” as distinct from the calendar we usually use to measure our age, might have more predictive power than the number itself. 

There are numerous molecular clocks, such as telomere length, that not only correlate with calendar age but are superior to calendar age in predicting age-related complications. Testing telomere length typically requires a blood sample — and remains costly. But we can use other sources to estimate age; how about a photo?

I mean, we do this all the time when we meet someone new or, as a physician, when we meet a new patient. I have often written that a patient “appears younger than their stated age,” and we’ve all had the experience of hearing how old someone is and being shocked. I mean, have you seen Sharon Stone recently? She’s 66 years old. Okay — to be fair, there might be some outside help there. But you get the point.

Back to the Cell Metabolism paper. Researchers report on multiple algorithms to obtain an “age” from a picture of an individual’s face. 

The first algorithm is pretty straightforward. Researchers collected 2811 images, all of Han Chinese individuals ranging in age from 20 to 90 years, and reconstructed a 3D facial map from those. 

memubrocheposwowrutaphewrowrimijebrauulathaleswot

prosterechiwremedrijatreclewrivudruwabruluphestespepustostuwruslunusliprukibejifrireshichethupiphemohothastesiwepriseputreualachigovusheruchodrenespestestepebeniphesivuchabrewrajichuphadrililicludrop

phatritribeuacrispicishabrejajuchephebrihedricevoshavivevospitheshuvotretegutrobujawoclodrirekuboswestekiclamacrawrijaveuithejabruvasistebrasicrugonetrowowuuishecropholiclumabristanawreswushislebaphaprihewreshagubreshiclicredrugostubrilegatrid

vatuthoviclobrauucushosudruswudevudrocetujoshoclouibastouetomacafrepreduprehachiwrewiprespirucacleslestisusposholemislunauutrocetetristiclejagewrehisloslecrithewru

thiprapesliposhuphidracloricucluwrispichikilatrehuuubiphadrumuslihouudrupakaprochadidrebijoj

be

swiprabuwroceslidrowruthoshodrulapropithuuucapilechuchoribubrathujireswovifrophuswemaslowruswijajadihogaspabestetrigupreclekushefrowaphowruspupuvatrataspeprolidecuwrowrafratejithucawodisowetinetodreche

br

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

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

This transcript has been edited for clarity. 

My oldest daughter is at sleepaway camp for a couple of weeks, and the camp has a photographer who goes around all day taking pictures of the kids, which get uploaded to a private Facebook group. In the past, I would go online every day (or, okay, several times a day) and scroll through all those pictures looking for one that features my kid. 

I don’t have to do that anymore. This year, I simply uploaded a picture of my daughter to an app and artificial intelligence (AI) takes care of the rest, recognizing her face amidst the sea of smiling children, and flagging just those photos for me to peruse. It’s amazing, really. And a bit scary.

The fact that facial recognition has penetrated the summer camp market should tell you that the tech is truly ubiquitous. But today we’re going to think a bit more about what AI can do with a picture of your face, because the power of facial recognition is not just skin deep.

What’s got me hot and bothered about facial images is this paper, appearing in Cell Metabolism, which adds a new layer to the standard facial-analysis playbook: facial temperature.

To understand this paper, you need to understand a whole field of research that is developing various different “clocks” for age. 

It turns out that age really is just a number. Our cells, our proteins, our biochemistry can be analyzed to give different numbers. These “clocks,” as distinct from the calendar we usually use to measure our age, might have more predictive power than the number itself. 

There are numerous molecular clocks, such as telomere length, that not only correlate with calendar age but are superior to calendar age in predicting age-related complications. Testing telomere length typically requires a blood sample — and remains costly. But we can use other sources to estimate age; how about a photo?

I mean, we do this all the time when we meet someone new or, as a physician, when we meet a new patient. I have often written that a patient “appears younger than their stated age,” and we’ve all had the experience of hearing how old someone is and being shocked. I mean, have you seen Sharon Stone recently? She’s 66 years old. Okay — to be fair, there might be some outside help there. But you get the point.

Back to the Cell Metabolism paper. Researchers report on multiple algorithms to obtain an “age” from a picture of an individual’s face. 

The first algorithm is pretty straightforward. Researchers collected 2811 images, all of Han Chinese individuals ranging in age from 20 to 90 years, and reconstructed a 3D facial map from those. 

memubrocheposwowrutaphewrowrimijebrauulathaleswot

prosterechiwremedrijatreclewrivudruwabruluphestespepustostuwruslunusliprukibejifrireshichethupiphemohothastesiwepriseputreualachigovusheruchodrenespestestepebeniphesivuchabrewrajichuphadrililicludrop

phatritribeuacrispicishabrejajuchephebrihedricevoshavivevospitheshuvotretegutrobujawoclodrirekuboswestekiclamacrawrijaveuithejabruvasistebrasicrugonetrowowuuishecropholiclumabristanawreswushislebaphaprihewreshagubreshiclicredrugostubrilegatrid

vatuthoviclobrauucushosudruswudevudrocetujoshoclouibastouetomacafrepreduprehachiwrewiprespirucacleslestisusposholemislunauutrocetetristiclejagewrehisloslecrithewru

thiprapesliposhuphidracloricucluwrispichikilatrehuuubiphadrumuslihouudrupakaprochadidrebijoj

be

swiprabuwroceslidrowruthoshodrulapropithuuucapilechuchoribubrathujireswovifrophuswemaslowruswijajadihogaspabestetrigupreclekushefrowaphowruspupuvatrataspeprolidecuwrowrafratejithucawodisowetinetodreche

br

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

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

ORLANDO, FLORIDA — What to prioritize first in managing early diabetes? That was the question debated on an expert panel at the American Diabetes Association (ADA) 84th Scientific Sessions, with impassioned responses ranging from a plea to “treat obesity first,” to a James Carville–inspired counterpoint of “it’s the glucose, stupid.” 

With a focus on preventing complications and inducing remission rounding out the four positions argued, Session Moderator Ravi Retnakaran, MD, of the University of Toronto, noted that the options reflect the tricky choices clinicians treating patients with diabetes are pressed to make on a daily basis.

“In clinical decision-making [for early diabetes], we are faced with weighing each of these variables for the individual patient, and while all are good options, strong arguments can be made for prioritizing each — with the potential of each choice to influence or improve all of the others,” Dr. Retnakaran told this news organization.
 

Which to Prioritize First?

Making the obesity first argument, Ania M. Jastreboff, MD, PhD, associate professor and director of the Yale Obesity Research Center at Yale School of Medicine, New Haven, Connecticut, noted the striking statistic that nearly 90% of people with type 2 diabetes have overweight or obesity and discussed the ever-expanding data showing the benefits of drugs including glucagon-like peptide 1 (GLP-1) receptor agonists not just in weight loss but also in kidney, cardiovascular, and, as presented at the meeting, sleep apnea improvement.

She contrasted the experiences of two patients with obesity: One treated for the obesity upon type 2 diagnosis — who had a quick normalization of lipids and hypertension soon after the obesity treatment — and the other presenting after 10 years with type 2 diabetes — who was on therapy for hypertension and hyperlipidemia but not for obesity and whose diseases were not as easily treated by that point.

“Why are we treating all the downstream effects and we’re not treating the disease that is potentially the root cause of all these other diseases?” Dr. Jastreboff said.
 

Complications?

Arguing in favor of focusing on complications, Roopa Mehta, MD, PhD, with the department of endocrinology and metabolism at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, made the case that stakes don’t get any higher in diabetes than when it comes the looming threat of potentially fatal complications.

Acute myocardial infarction, stroke, amputation, and end-stage renal disease are all on the list of unwanted outcomes and need to be considered even in the earliest stages, as data show early onset type 2 diabetes is linked to life expectancy.

“The main goal of management has always been to prevent complications,” she noted. Citing ADA guidelines, Dr. Mehta underscored the benefits of first- and second-line therapy of metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and GLP-1 receptor agonists for most patients.
 

Remission?

Discussing the priority of putting patients into disease remission, Roy Taylor, MD, professor of medicine and metabolism at Newcastle University and Newcastle Hospitals NHS in Newcastle upon Tyne, England, and author of the book Life Without Diabetes, focused on an evidence-based alternative to achieving remission — a nonpharmacologic approach that avoids costly and sometimes inaccessible drugs.

In the intervention, described in the DiRECT randomized trial and subsequently in the UK National Health Service Type 2 Diabetes Path to Remission Program, patients with overweight or obesity were placed on a highly restrictive diet of just 800-900 calories a day for 12-20 weeks, followed by maintenance for 12 months, and they not only achieved weight loss but also achieved diabetes remission, in some cases long term.

Acknowledging that “this is not for everyone,” Dr. Taylor asserted that “we have to realize there is a substantial minority of people who want to be healthy but who don’t want to be medicalized,” he said.

“They want their health, and they can do extremely well.”
 

Glucose?

In taking his self-titled “it’s the glucose, stupid” stand, David M. Nathan, MD, of the Diabetes Center, Massachusetts General Hospital, Harvard Medical School, in Boston, cited extensive evidence showing that early intensive blood glucose control with treatment including sulfonylureas, insulin, or metformin significantly reduced the risk for complications in type 2 diabetes 15 or more years later, including renal failure, blindness, amputation, and myocardial infarctions, in addition to a reduction in diabetes-related death.

“In many of these studies, you saw the benefit even in the setting of weight-gain,” Dr. Nathan underscored.

He further noted the “sobering” findings of the Look AHEAD study, which had to be stopped due to futility when an intensive lifestyle/weight loss intervention showed no significant benefits in terms of cardiovascular disease in people with type 2 diabetes at a median follow-up of 9.6 years.

Ultimately, “diabetes, type 1 and type 2, remains a gluco-centric disease,” Dr. Nathan asserted. “Hyperglycemia is the only universal link between all forms of diabetes and mortality, and the long-term complications of diabetes are intimately associated with hyperglycemia.”
 

Tackling the Caveats

The ensuing panel discussion did not fail to deliver in delving into key areas of contention, particularly in terms of GLP-1 treatment.

Regarding a lack of data on the potential long-term effects of GLP-1s: “Yes, there are a huge number of studies [on GLP-1 receptor agonists], but they are, in general, over short periods of time and driven by pharma, who get in and get out as quickly as they can and have little in the way of interest to do comparative effectiveness studies,” Dr. Nathan argued.

“Meanwhile, this is like the crack cocaine of medications — patients have to stay on it for a lifetime or they will regain the weight — are you concerned at all about a lifetime of exposure to GLP-1 [drugs]?” he asked the panel.

Dr. Jastreboff responded that the first GLP-1 receptor agonist medications were approved in 2005, nearly 20 years ago, by the US Food and Drug Administration.

“Do I think we need long-term lifetime data? Absolutely,” she said. “We need to do our due diligence, we need to be careful, we need to monitor patients, and when and if there are signals, we need to follow them.”

What about the notorious gastrointestinal side effects of the drugs? “A majority of them are mitigated by slow up-titration,” Dr. Jastreboff noted.

“If patients have nausea, I do not go up [in dose]. I invite patients to tell me if they’re having vomiting because I don’t want anybody to have it, and I can count on one hand how many of my patients do.”

Dr. Mehta added the concern that as the drugs’ popularity soars, “a lot of doctors don’t know when they need to put the brakes on [weight coming off too quickly].”

She underscored that “we are not treating obesity for weight loss or for cosmetic reasons — this is about optimizing health.”

Dr. Jastreboff noted that in her practice, “I down-titrate if they’re losing weight too quickly.”

“If the patient is losing more than 1% per week of their body weight, then I slow down to make sure they’re getting the nutrients that they need, that they have enough energy to exercise, and that they’re prioritizing protein and fruits and vegetables in their diet.

“We just need to go slow, and yes, we need to follow them long term,” she said.

Chiming in from the audience, Julio Rosenstock, MD, a recognized thought leader in type 2 diabetes, offered his own take on the issues, describing Dr. Taylor’s very low–calorie diet suggestion as “not realistic” and Dr. Nathan’s glucose-first argument to be “stuck in the past.”

Based on modern-day evidence, “there is no reason on earth to start [diabetes treatment] with only metformin,” asserted Dr. Rosenstock, director of the Velocity Clinical Research center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.

“We need to start at the very least with metformin and a sodium-glucose cotransporter 2 (SGLT2) inhibitor from day 1, and then, if it’s affordable and there is access, with a GLP-1 receptor agonist,” he said.

“There is nothing better these days than those agents that consistently have shown a reduction of cardiovascular events and slowing of kidney disease progression.”

Overall, however, “I think you are all right,” he added, a sentiment shared by most.

Noting that the discussion as a whole represents a virtual sea change from the evidence-based options that would have been discussed only a decade ago, Dr. Retnakaran summed up his take-home message: “Stay tuned.

“You could easily see things changing in the next decade to come as we get more data and evidence to support what we ultimately should prioritize an early type 2 diabetes, so this is an exciting time.”

Dr. Retnakaran disclosed ties with Novo Nordisk, Boehringer Ingelheim, Novartis, Sanofi, and Eli Lilly. Dr. Jastreboff disclosed ties with Amgen, AstraZeneca, Boehringer Ingelheim, Biohaven, Eli Lilly, Intellihealth, Novo Nordisk, Pfizer, Regeneron, Scholar Rock, Structure Therapeutics, Terms Pharmaceutical, Weight Watchers, and Zealand Pharmaceuticals. Dr. Roopa had relationships with Novo Nordisk, Boehringer Ingelheim, Amgen, AstraZeneca, Eli Lilly, Silanes, and Sanofi. Dr. Taylor received lecture fees from Novartis, Lilly, Abbott, and Nestle Health and research funding from Diabetes UK and is an advisor to Fast800. Dr. Rosenstock reported relationships with Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Oramed, Structure Therapeutics, Novartis, Novo Nordisk, Pfizer, Ragor, and Sanofi. Dr. Nathan had no disclosures to report.
 

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

ORLANDO, FLORIDA — What to prioritize first in managing early diabetes? That was the question debated on an expert panel at the American Diabetes Association (ADA) 84th Scientific Sessions, with impassioned responses ranging from a plea to “treat obesity first,” to a James Carville–inspired counterpoint of “it’s the glucose, stupid.” 

With a focus on preventing complications and inducing remission rounding out the four positions argued, Session Moderator Ravi Retnakaran, MD, of the University of Toronto, noted that the options reflect the tricky choices clinicians treating patients with diabetes are pressed to make on a daily basis.

“In clinical decision-making [for early diabetes], we are faced with weighing each of these variables for the individual patient, and while all are good options, strong arguments can be made for prioritizing each — with the potential of each choice to influence or improve all of the others,” Dr. Retnakaran told this news organization.
 

Which to Prioritize First?

Making the obesity first argument, Ania M. Jastreboff, MD, PhD, associate professor and director of the Yale Obesity Research Center at Yale School of Medicine, New Haven, Connecticut, noted the striking statistic that nearly 90% of people with type 2 diabetes have overweight or obesity and discussed the ever-expanding data showing the benefits of drugs including glucagon-like peptide 1 (GLP-1) receptor agonists not just in weight loss but also in kidney, cardiovascular, and, as presented at the meeting, sleep apnea improvement.

She contrasted the experiences of two patients with obesity: One treated for the obesity upon type 2 diagnosis — who had a quick normalization of lipids and hypertension soon after the obesity treatment — and the other presenting after 10 years with type 2 diabetes — who was on therapy for hypertension and hyperlipidemia but not for obesity and whose diseases were not as easily treated by that point.

“Why are we treating all the downstream effects and we’re not treating the disease that is potentially the root cause of all these other diseases?” Dr. Jastreboff said.
 

Complications?

Arguing in favor of focusing on complications, Roopa Mehta, MD, PhD, with the department of endocrinology and metabolism at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, made the case that stakes don’t get any higher in diabetes than when it comes the looming threat of potentially fatal complications.

Acute myocardial infarction, stroke, amputation, and end-stage renal disease are all on the list of unwanted outcomes and need to be considered even in the earliest stages, as data show early onset type 2 diabetes is linked to life expectancy.

“The main goal of management has always been to prevent complications,” she noted. Citing ADA guidelines, Dr. Mehta underscored the benefits of first- and second-line therapy of metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and GLP-1 receptor agonists for most patients.
 

Remission?

Discussing the priority of putting patients into disease remission, Roy Taylor, MD, professor of medicine and metabolism at Newcastle University and Newcastle Hospitals NHS in Newcastle upon Tyne, England, and author of the book Life Without Diabetes, focused on an evidence-based alternative to achieving remission — a nonpharmacologic approach that avoids costly and sometimes inaccessible drugs.

In the intervention, described in the DiRECT randomized trial and subsequently in the UK National Health Service Type 2 Diabetes Path to Remission Program, patients with overweight or obesity were placed on a highly restrictive diet of just 800-900 calories a day for 12-20 weeks, followed by maintenance for 12 months, and they not only achieved weight loss but also achieved diabetes remission, in some cases long term.

Acknowledging that “this is not for everyone,” Dr. Taylor asserted that “we have to realize there is a substantial minority of people who want to be healthy but who don’t want to be medicalized,” he said.

“They want their health, and they can do extremely well.”
 

Glucose?

In taking his self-titled “it’s the glucose, stupid” stand, David M. Nathan, MD, of the Diabetes Center, Massachusetts General Hospital, Harvard Medical School, in Boston, cited extensive evidence showing that early intensive blood glucose control with treatment including sulfonylureas, insulin, or metformin significantly reduced the risk for complications in type 2 diabetes 15 or more years later, including renal failure, blindness, amputation, and myocardial infarctions, in addition to a reduction in diabetes-related death.

“In many of these studies, you saw the benefit even in the setting of weight-gain,” Dr. Nathan underscored.

He further noted the “sobering” findings of the Look AHEAD study, which had to be stopped due to futility when an intensive lifestyle/weight loss intervention showed no significant benefits in terms of cardiovascular disease in people with type 2 diabetes at a median follow-up of 9.6 years.

Ultimately, “diabetes, type 1 and type 2, remains a gluco-centric disease,” Dr. Nathan asserted. “Hyperglycemia is the only universal link between all forms of diabetes and mortality, and the long-term complications of diabetes are intimately associated with hyperglycemia.”
 

Tackling the Caveats

The ensuing panel discussion did not fail to deliver in delving into key areas of contention, particularly in terms of GLP-1 treatment.

Regarding a lack of data on the potential long-term effects of GLP-1s: “Yes, there are a huge number of studies [on GLP-1 receptor agonists], but they are, in general, over short periods of time and driven by pharma, who get in and get out as quickly as they can and have little in the way of interest to do comparative effectiveness studies,” Dr. Nathan argued.

“Meanwhile, this is like the crack cocaine of medications — patients have to stay on it for a lifetime or they will regain the weight — are you concerned at all about a lifetime of exposure to GLP-1 [drugs]?” he asked the panel.

Dr. Jastreboff responded that the first GLP-1 receptor agonist medications were approved in 2005, nearly 20 years ago, by the US Food and Drug Administration.

“Do I think we need long-term lifetime data? Absolutely,” she said. “We need to do our due diligence, we need to be careful, we need to monitor patients, and when and if there are signals, we need to follow them.”

What about the notorious gastrointestinal side effects of the drugs? “A majority of them are mitigated by slow up-titration,” Dr. Jastreboff noted.

“If patients have nausea, I do not go up [in dose]. I invite patients to tell me if they’re having vomiting because I don’t want anybody to have it, and I can count on one hand how many of my patients do.”

Dr. Mehta added the concern that as the drugs’ popularity soars, “a lot of doctors don’t know when they need to put the brakes on [weight coming off too quickly].”

She underscored that “we are not treating obesity for weight loss or for cosmetic reasons — this is about optimizing health.”

Dr. Jastreboff noted that in her practice, “I down-titrate if they’re losing weight too quickly.”

“If the patient is losing more than 1% per week of their body weight, then I slow down to make sure they’re getting the nutrients that they need, that they have enough energy to exercise, and that they’re prioritizing protein and fruits and vegetables in their diet.

“We just need to go slow, and yes, we need to follow them long term,” she said.

Chiming in from the audience, Julio Rosenstock, MD, a recognized thought leader in type 2 diabetes, offered his own take on the issues, describing Dr. Taylor’s very low–calorie diet suggestion as “not realistic” and Dr. Nathan’s glucose-first argument to be “stuck in the past.”

Based on modern-day evidence, “there is no reason on earth to start [diabetes treatment] with only metformin,” asserted Dr. Rosenstock, director of the Velocity Clinical Research center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.

“We need to start at the very least with metformin and a sodium-glucose cotransporter 2 (SGLT2) inhibitor from day 1, and then, if it’s affordable and there is access, with a GLP-1 receptor agonist,” he said.

“There is nothing better these days than those agents that consistently have shown a reduction of cardiovascular events and slowing of kidney disease progression.”

Overall, however, “I think you are all right,” he added, a sentiment shared by most.

Noting that the discussion as a whole represents a virtual sea change from the evidence-based options that would have been discussed only a decade ago, Dr. Retnakaran summed up his take-home message: “Stay tuned.

“You could easily see things changing in the next decade to come as we get more data and evidence to support what we ultimately should prioritize an early type 2 diabetes, so this is an exciting time.”

Dr. Retnakaran disclosed ties with Novo Nordisk, Boehringer Ingelheim, Novartis, Sanofi, and Eli Lilly. Dr. Jastreboff disclosed ties with Amgen, AstraZeneca, Boehringer Ingelheim, Biohaven, Eli Lilly, Intellihealth, Novo Nordisk, Pfizer, Regeneron, Scholar Rock, Structure Therapeutics, Terms Pharmaceutical, Weight Watchers, and Zealand Pharmaceuticals. Dr. Roopa had relationships with Novo Nordisk, Boehringer Ingelheim, Amgen, AstraZeneca, Eli Lilly, Silanes, and Sanofi. Dr. Taylor received lecture fees from Novartis, Lilly, Abbott, and Nestle Health and research funding from Diabetes UK and is an advisor to Fast800. Dr. Rosenstock reported relationships with Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Oramed, Structure Therapeutics, Novartis, Novo Nordisk, Pfizer, Ragor, and Sanofi. Dr. Nathan had no disclosures to report.
 

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

ORLANDO, FLORIDA — What to prioritize first in managing early diabetes? That was the question debated on an expert panel at the American Diabetes Association (ADA) 84th Scientific Sessions, with impassioned responses ranging from a plea to “treat obesity first,” to a James Carville–inspired counterpoint of “it’s the glucose, stupid.” 

With a focus on preventing complications and inducing remission rounding out the four positions argued, Session Moderator Ravi Retnakaran, MD, of the University of Toronto, noted that the options reflect the tricky choices clinicians treating patients with diabetes are pressed to make on a daily basis.

“In clinical decision-making [for early diabetes], we are faced with weighing each of these variables for the individual patient, and while all are good options, strong arguments can be made for prioritizing each — with the potential of each choice to influence or improve all of the others,” Dr. Retnakaran told this news organization.
 

Which to Prioritize First?

Making the obesity first argument, Ania M. Jastreboff, MD, PhD, associate professor and director of the Yale Obesity Research Center at Yale School of Medicine, New Haven, Connecticut, noted the striking statistic that nearly 90% of people with type 2 diabetes have overweight or obesity and discussed the ever-expanding data showing the benefits of drugs including glucagon-like peptide 1 (GLP-1) receptor agonists not just in weight loss but also in kidney, cardiovascular, and, as presented at the meeting, sleep apnea improvement.

She contrasted the experiences of two patients with obesity: One treated for the obesity upon type 2 diagnosis — who had a quick normalization of lipids and hypertension soon after the obesity treatment — and the other presenting after 10 years with type 2 diabetes — who was on therapy for hypertension and hyperlipidemia but not for obesity and whose diseases were not as easily treated by that point.

“Why are we treating all the downstream effects and we’re not treating the disease that is potentially the root cause of all these other diseases?” Dr. Jastreboff said.
 

Complications?

Arguing in favor of focusing on complications, Roopa Mehta, MD, PhD, with the department of endocrinology and metabolism at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, made the case that stakes don’t get any higher in diabetes than when it comes the looming threat of potentially fatal complications.

Acute myocardial infarction, stroke, amputation, and end-stage renal disease are all on the list of unwanted outcomes and need to be considered even in the earliest stages, as data show early onset type 2 diabetes is linked to life expectancy.

“The main goal of management has always been to prevent complications,” she noted. Citing ADA guidelines, Dr. Mehta underscored the benefits of first- and second-line therapy of metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and GLP-1 receptor agonists for most patients.
 

Remission?

Discussing the priority of putting patients into disease remission, Roy Taylor, MD, professor of medicine and metabolism at Newcastle University and Newcastle Hospitals NHS in Newcastle upon Tyne, England, and author of the book Life Without Diabetes, focused on an evidence-based alternative to achieving remission — a nonpharmacologic approach that avoids costly and sometimes inaccessible drugs.

In the intervention, described in the DiRECT randomized trial and subsequently in the UK National Health Service Type 2 Diabetes Path to Remission Program, patients with overweight or obesity were placed on a highly restrictive diet of just 800-900 calories a day for 12-20 weeks, followed by maintenance for 12 months, and they not only achieved weight loss but also achieved diabetes remission, in some cases long term.

Acknowledging that “this is not for everyone,” Dr. Taylor asserted that “we have to realize there is a substantial minority of people who want to be healthy but who don’t want to be medicalized,” he said.

“They want their health, and they can do extremely well.”
 

Glucose?

In taking his self-titled “it’s the glucose, stupid” stand, David M. Nathan, MD, of the Diabetes Center, Massachusetts General Hospital, Harvard Medical School, in Boston, cited extensive evidence showing that early intensive blood glucose control with treatment including sulfonylureas, insulin, or metformin significantly reduced the risk for complications in type 2 diabetes 15 or more years later, including renal failure, blindness, amputation, and myocardial infarctions, in addition to a reduction in diabetes-related death.

“In many of these studies, you saw the benefit even in the setting of weight-gain,” Dr. Nathan underscored.

He further noted the “sobering” findings of the Look AHEAD study, which had to be stopped due to futility when an intensive lifestyle/weight loss intervention showed no significant benefits in terms of cardiovascular disease in people with type 2 diabetes at a median follow-up of 9.6 years.

Ultimately, “diabetes, type 1 and type 2, remains a gluco-centric disease,” Dr. Nathan asserted. “Hyperglycemia is the only universal link between all forms of diabetes and mortality, and the long-term complications of diabetes are intimately associated with hyperglycemia.”
 

Tackling the Caveats

The ensuing panel discussion did not fail to deliver in delving into key areas of contention, particularly in terms of GLP-1 treatment.

Regarding a lack of data on the potential long-term effects of GLP-1s: “Yes, there are a huge number of studies [on GLP-1 receptor agonists], but they are, in general, over short periods of time and driven by pharma, who get in and get out as quickly as they can and have little in the way of interest to do comparative effectiveness studies,” Dr. Nathan argued.

“Meanwhile, this is like the crack cocaine of medications — patients have to stay on it for a lifetime or they will regain the weight — are you concerned at all about a lifetime of exposure to GLP-1 [drugs]?” he asked the panel.

Dr. Jastreboff responded that the first GLP-1 receptor agonist medications were approved in 2005, nearly 20 years ago, by the US Food and Drug Administration.

“Do I think we need long-term lifetime data? Absolutely,” she said. “We need to do our due diligence, we need to be careful, we need to monitor patients, and when and if there are signals, we need to follow them.”

What about the notorious gastrointestinal side effects of the drugs? “A majority of them are mitigated by slow up-titration,” Dr. Jastreboff noted.

“If patients have nausea, I do not go up [in dose]. I invite patients to tell me if they’re having vomiting because I don’t want anybody to have it, and I can count on one hand how many of my patients do.”

Dr. Mehta added the concern that as the drugs’ popularity soars, “a lot of doctors don’t know when they need to put the brakes on [weight coming off too quickly].”

She underscored that “we are not treating obesity for weight loss or for cosmetic reasons — this is about optimizing health.”

Dr. Jastreboff noted that in her practice, “I down-titrate if they’re losing weight too quickly.”

“If the patient is losing more than 1% per week of their body weight, then I slow down to make sure they’re getting the nutrients that they need, that they have enough energy to exercise, and that they’re prioritizing protein and fruits and vegetables in their diet.

“We just need to go slow, and yes, we need to follow them long term,” she said.

Chiming in from the audience, Julio Rosenstock, MD, a recognized thought leader in type 2 diabetes, offered his own take on the issues, describing Dr. Taylor’s very low–calorie diet suggestion as “not realistic” and Dr. Nathan’s glucose-first argument to be “stuck in the past.”

Based on modern-day evidence, “there is no reason on earth to start [diabetes treatment] with only metformin,” asserted Dr. Rosenstock, director of the Velocity Clinical Research center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.

“We need to start at the very least with metformin and a sodium-glucose cotransporter 2 (SGLT2) inhibitor from day 1, and then, if it’s affordable and there is access, with a GLP-1 receptor agonist,” he said.

“There is nothing better these days than those agents that consistently have shown a reduction of cardiovascular events and slowing of kidney disease progression.”

Overall, however, “I think you are all right,” he added, a sentiment shared by most.

Noting that the discussion as a whole represents a virtual sea change from the evidence-based options that would have been discussed only a decade ago, Dr. Retnakaran summed up his take-home message: “Stay tuned.

“You could easily see things changing in the next decade to come as we get more data and evidence to support what we ultimately should prioritize an early type 2 diabetes, so this is an exciting time.”

Dr. Retnakaran disclosed ties with Novo Nordisk, Boehringer Ingelheim, Novartis, Sanofi, and Eli Lilly. Dr. Jastreboff disclosed ties with Amgen, AstraZeneca, Boehringer Ingelheim, Biohaven, Eli Lilly, Intellihealth, Novo Nordisk, Pfizer, Regeneron, Scholar Rock, Structure Therapeutics, Terms Pharmaceutical, Weight Watchers, and Zealand Pharmaceuticals. Dr. Roopa had relationships with Novo Nordisk, Boehringer Ingelheim, Amgen, AstraZeneca, Eli Lilly, Silanes, and Sanofi. Dr. Taylor received lecture fees from Novartis, Lilly, Abbott, and Nestle Health and research funding from Diabetes UK and is an advisor to Fast800. Dr. Rosenstock reported relationships with Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Oramed, Structure Therapeutics, Novartis, Novo Nordisk, Pfizer, Ragor, and Sanofi. Dr. Nathan had no disclosures to report.
 

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