Key clinical point: The combination of the prognostic mantle cell lymphoma (MCL) International Prognostic Index (MIPI) with biological risk factors Ki-67 and p53 expression identifies a subset of patients with MCL having poor prognosis.

Major finding: Patients with high combined MIPI (MIPI-c) or p53 expression > 50% (high-risk disease) vs low, low-intermediate, or high-intermediate MIPI-c and p53 expression ≤ 50% (low-risk disease) had significantly shorter median failure-free survival (hazard ratio [HR] 2.97) and overall survival (HR 3.69) at median follow-ups of 9.6 and 9.4 years, respectively (both P < .0001). The results were confirmed in validation cohorts.

Study details: The training cohort included 684 patients with MCL from the MCL-Younger and MCL-Elderly trials with evaluable data for Ki-67 or p53; patients were classified as having high-risk or low-risk disease. The validation cohorts included 230 and 44 patients from the MCL0208 and Nordic-MCL4 trials, respectively.

Disclosures: This study did not receive any funding. Some authors declared serving on advisory boards or speakers’ bureaus of or receiving research funding, consultancy fees, or honoraria from various sources.

Source: Scheubeck G et al. Clinical outcome of mantle cell lymphoma patients with high-risk disease (high-risk MIPI-c or high p53 expression). Leukemia. 2023;37(9):1887-1894 (Jul 26). doi: 10.1038/s41375-023-01977-y

Key clinical point: The combination of the prognostic mantle cell lymphoma (MCL) International Prognostic Index (MIPI) with biological risk factors Ki-67 and p53 expression identifies a subset of patients with MCL having poor prognosis.

Major finding: Patients with high combined MIPI (MIPI-c) or p53 expression > 50% (high-risk disease) vs low, low-intermediate, or high-intermediate MIPI-c and p53 expression ≤ 50% (low-risk disease) had significantly shorter median failure-free survival (hazard ratio [HR] 2.97) and overall survival (HR 3.69) at median follow-ups of 9.6 and 9.4 years, respectively (both P < .0001). The results were confirmed in validation cohorts.

Study details: The training cohort included 684 patients with MCL from the MCL-Younger and MCL-Elderly trials with evaluable data for Ki-67 or p53; patients were classified as having high-risk or low-risk disease. The validation cohorts included 230 and 44 patients from the MCL0208 and Nordic-MCL4 trials, respectively.

Disclosures: This study did not receive any funding. Some authors declared serving on advisory boards or speakers’ bureaus of or receiving research funding, consultancy fees, or honoraria from various sources.

Source: Scheubeck G et al. Clinical outcome of mantle cell lymphoma patients with high-risk disease (high-risk MIPI-c or high p53 expression). Leukemia. 2023;37(9):1887-1894 (Jul 26). doi: 10.1038/s41375-023-01977-y

Key clinical point: The combination of the prognostic mantle cell lymphoma (MCL) International Prognostic Index (MIPI) with biological risk factors Ki-67 and p53 expression identifies a subset of patients with MCL having poor prognosis.

Major finding: Patients with high combined MIPI (MIPI-c) or p53 expression > 50% (high-risk disease) vs low, low-intermediate, or high-intermediate MIPI-c and p53 expression ≤ 50% (low-risk disease) had significantly shorter median failure-free survival (hazard ratio [HR] 2.97) and overall survival (HR 3.69) at median follow-ups of 9.6 and 9.4 years, respectively (both P < .0001). The results were confirmed in validation cohorts.

Study details: The training cohort included 684 patients with MCL from the MCL-Younger and MCL-Elderly trials with evaluable data for Ki-67 or p53; patients were classified as having high-risk or low-risk disease. The validation cohorts included 230 and 44 patients from the MCL0208 and Nordic-MCL4 trials, respectively.

Disclosures: This study did not receive any funding. Some authors declared serving on advisory boards or speakers’ bureaus of or receiving research funding, consultancy fees, or honoraria from various sources.

Source: Scheubeck G et al. Clinical outcome of mantle cell lymphoma patients with high-risk disease (high-risk MIPI-c or high p53 expression). Leukemia. 2023;37(9):1887-1894 (Jul 26). doi: 10.1038/s41375-023-01977-y

Key clinical point: Acalabrutinib demonstrates favorable long-term efficacy and safety in patients with relapsed or refractory mantle cell lymphoma (MCL), including those with poor prognostic factors.

Major finding: The overall and complete response rates were 81.5% (95% CI 73.5%-87.9%) and 47.6% (95% CI 38.5%-56.7%), respectively. After a 38.1-month median follow-up, median duration of response and progression-free survival were 28.6 (95% CI 17.5-39.1) and 22.0 (95% CI 16.6-33.3) months, respectively. No new safety signals were observed.

Study details: The data represent the final results of the phase 2 ACE-LY-004 study of 124 adult patients with MCL, including those with poor prognostic factors, such as blastoid or pleomorphic morphology and Ki-67 index of >30%, who relapsed after or were refractory to ≤ 5 previous therapies and received acalabrutinib twice daily.

Disclosures: This study was funded by AstraZeneca. Some authors declared serving as consultants, advisors, or speakers for and receiving research funds or travel or accommodation expenses from various sources, including AstraZeneca. Two authors declared being employees or equity holders of AstraZeneca.

Source: Le Gouill S et al. Final results and overall survival data from a phase II study of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma, including those with poor prognostic factors. Haematologica. 2023 (Jul 20). doi: 10.3324/haematol.2022.282469

Key clinical point: Acalabrutinib demonstrates favorable long-term efficacy and safety in patients with relapsed or refractory mantle cell lymphoma (MCL), including those with poor prognostic factors.

Major finding: The overall and complete response rates were 81.5% (95% CI 73.5%-87.9%) and 47.6% (95% CI 38.5%-56.7%), respectively. After a 38.1-month median follow-up, median duration of response and progression-free survival were 28.6 (95% CI 17.5-39.1) and 22.0 (95% CI 16.6-33.3) months, respectively. No new safety signals were observed.

Study details: The data represent the final results of the phase 2 ACE-LY-004 study of 124 adult patients with MCL, including those with poor prognostic factors, such as blastoid or pleomorphic morphology and Ki-67 index of >30%, who relapsed after or were refractory to ≤ 5 previous therapies and received acalabrutinib twice daily.

Disclosures: This study was funded by AstraZeneca. Some authors declared serving as consultants, advisors, or speakers for and receiving research funds or travel or accommodation expenses from various sources, including AstraZeneca. Two authors declared being employees or equity holders of AstraZeneca.

Source: Le Gouill S et al. Final results and overall survival data from a phase II study of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma, including those with poor prognostic factors. Haematologica. 2023 (Jul 20). doi: 10.3324/haematol.2022.282469

Key clinical point: Acalabrutinib demonstrates favorable long-term efficacy and safety in patients with relapsed or refractory mantle cell lymphoma (MCL), including those with poor prognostic factors.

Major finding: The overall and complete response rates were 81.5% (95% CI 73.5%-87.9%) and 47.6% (95% CI 38.5%-56.7%), respectively. After a 38.1-month median follow-up, median duration of response and progression-free survival were 28.6 (95% CI 17.5-39.1) and 22.0 (95% CI 16.6-33.3) months, respectively. No new safety signals were observed.

Study details: The data represent the final results of the phase 2 ACE-LY-004 study of 124 adult patients with MCL, including those with poor prognostic factors, such as blastoid or pleomorphic morphology and Ki-67 index of >30%, who relapsed after or were refractory to ≤ 5 previous therapies and received acalabrutinib twice daily.

Disclosures: This study was funded by AstraZeneca. Some authors declared serving as consultants, advisors, or speakers for and receiving research funds or travel or accommodation expenses from various sources, including AstraZeneca. Two authors declared being employees or equity holders of AstraZeneca.

Source: Le Gouill S et al. Final results and overall survival data from a phase II study of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma, including those with poor prognostic factors. Haematologica. 2023 (Jul 20). doi: 10.3324/haematol.2022.282469

The Centers for Disease Control and Prevention is tracking a newly discovered strain of COVID-19 called BA.2.86.

On Aug. 17, the agency posted on X, formerly known as Twitter, that the lineage has been detected in the United States, Denmark, and Israel. 

“As we learn more about BA.2.86, CDC’s advice on protecting yourself from COVID-19 remains the same,” the CDC said on X. 

A case of BA.2.86 was detected at a laboratory at the University of Michigan, CBS News reported. It’s not clear how the university obtained the sample that was sequenced. A case was also detected in the United Kingdom, the news outlet said. 

The World Health Organization is also tracking BA.2.86 and has classified it as a “variant under monitoring.” 

“More data are needed to understand this COVID-19 variant and the extent of its spread, but the number of mutations warrants attention. WHO will update countries and the public as we learn more,” the WHO said on X.

The strain is so new that scientists don’t know if BA.2.86 is more easily spread, causes more severe symptoms than existing strains, or will be more resistant to vaccines and natural immunity developed over the last few years. 

Early research indicates BA.2.86 “will have equal or greater escape than XBB.1.5 from antibodies elicited by pre-Omicron and first-generation Omicron variants,” Jesse Bloom, PhD, a virologist at the Fred Hutchinson Cancer Center, said in a slide deck published Aug. 17. (XBB.1.5 is the Omicron subvariant that is targeted in the updated COVID booster shot to be released soon.)

Still, Dr. Bloom noted that “even if a highly mutated new variant like BA.2.86 starts to spread, we will be in a far better place than we were in 2020 and 2021, since most people have some immunity to SARS-CoV-2 now.”

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

The Centers for Disease Control and Prevention is tracking a newly discovered strain of COVID-19 called BA.2.86.

On Aug. 17, the agency posted on X, formerly known as Twitter, that the lineage has been detected in the United States, Denmark, and Israel. 

“As we learn more about BA.2.86, CDC’s advice on protecting yourself from COVID-19 remains the same,” the CDC said on X. 

A case of BA.2.86 was detected at a laboratory at the University of Michigan, CBS News reported. It’s not clear how the university obtained the sample that was sequenced. A case was also detected in the United Kingdom, the news outlet said. 

The World Health Organization is also tracking BA.2.86 and has classified it as a “variant under monitoring.” 

“More data are needed to understand this COVID-19 variant and the extent of its spread, but the number of mutations warrants attention. WHO will update countries and the public as we learn more,” the WHO said on X.

The strain is so new that scientists don’t know if BA.2.86 is more easily spread, causes more severe symptoms than existing strains, or will be more resistant to vaccines and natural immunity developed over the last few years. 

Early research indicates BA.2.86 “will have equal or greater escape than XBB.1.5 from antibodies elicited by pre-Omicron and first-generation Omicron variants,” Jesse Bloom, PhD, a virologist at the Fred Hutchinson Cancer Center, said in a slide deck published Aug. 17. (XBB.1.5 is the Omicron subvariant that is targeted in the updated COVID booster shot to be released soon.)

Still, Dr. Bloom noted that “even if a highly mutated new variant like BA.2.86 starts to spread, we will be in a far better place than we were in 2020 and 2021, since most people have some immunity to SARS-CoV-2 now.”

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

The Centers for Disease Control and Prevention is tracking a newly discovered strain of COVID-19 called BA.2.86.

On Aug. 17, the agency posted on X, formerly known as Twitter, that the lineage has been detected in the United States, Denmark, and Israel. 

“As we learn more about BA.2.86, CDC’s advice on protecting yourself from COVID-19 remains the same,” the CDC said on X. 

A case of BA.2.86 was detected at a laboratory at the University of Michigan, CBS News reported. It’s not clear how the university obtained the sample that was sequenced. A case was also detected in the United Kingdom, the news outlet said. 

The World Health Organization is also tracking BA.2.86 and has classified it as a “variant under monitoring.” 

“More data are needed to understand this COVID-19 variant and the extent of its spread, but the number of mutations warrants attention. WHO will update countries and the public as we learn more,” the WHO said on X.

The strain is so new that scientists don’t know if BA.2.86 is more easily spread, causes more severe symptoms than existing strains, or will be more resistant to vaccines and natural immunity developed over the last few years. 

Early research indicates BA.2.86 “will have equal or greater escape than XBB.1.5 from antibodies elicited by pre-Omicron and first-generation Omicron variants,” Jesse Bloom, PhD, a virologist at the Fred Hutchinson Cancer Center, said in a slide deck published Aug. 17. (XBB.1.5 is the Omicron subvariant that is targeted in the updated COVID booster shot to be released soon.)

Still, Dr. Bloom noted that “even if a highly mutated new variant like BA.2.86 starts to spread, we will be in a far better place than we were in 2020 and 2021, since most people have some immunity to SARS-CoV-2 now.”

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

Men and women with prediabetes, undiagnosed diabetes, and, notably, diagnosed diabetes were at higher risk of incident cardiovascular disease (CVD), whereas those with low-normal A1c were at lower risk of this in a large, 12-year observational study of UK Biobank data.

The results highlight “the need for strategies to reduce risk of CVD across the [glycemic] spectrum,” Christopher T. Rentsch, MPH, PhD, and colleagues wrote in their study, which was published in the The Lancet Regional Health – Europe.

The findings suggest “that excess [CVD] risks in both men and women were largely explained by modifiable factors and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications.

“Addressing these risk factors could reduce sex disparities in [glycemia]-related risks of CVD,” according to the researchers.

After the researchers accounted for age, the absolute rate of CVD events was higher among men than women (16.9 vs. 9.1 events per 1,000 person-years); however, the relative risk was higher among women than men.

Compared with men, women were more likely to have obesity (63% vs. 53%) and were less likely to be using antihypertensive medications (64% vs. 69%) or a statin (71% vs. 75%).

“This is the largest study to date to investigate sex differences in the risk of CVD across the glycemic spectrum,” the researchers noted.
 

“The lower the better”

“We uncovered compelling evidence that for blood sugar levels within the ‘normal’ range, it was a case of ‘the lower the better’ in protecting against heart disease,” Dr. Rentsch, assistant professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, told this news organization.

Compared with people with normal blood glucose levels, those with lower than normal levels were at 10% lower risk of developing any form of heart disease, he noted.

The study findings “support women being proactive in asking about medications like statins and antihypertensives as an option to help lower their [CVD] risk, if clinically appropriate,” Dr. Rentsch added.

“We found that men and women with diagnosed diabetes remained at elevated risk for three types of heart disease – coronary artery disease, stroke, and heart failure – even after accounting for a large number of sociodemographic, lifestyle, and clinical characteristics,” he pointed out.

However, “total cholesterol, family history of CVD, estimated glomerular filtration rate, and C-reactive protein had relatively little impact on explaining the risk of heart disease associated with blood sugar.”

“It is well established that being overweight can lead to higher blood sugar levels as well as higher blood pressure, these being factors that contribute to higher risk of heart attack and stroke,” Robert Storey, DM, professor of cardiology, University of Sheffield (England), told the UK Science Media Centre.

“This very large UK Biobank study,” he said, “shows that the higher heart risk associated with blood sugar can be detected at a very early stage along the path towards the abnormally high blood sugar levels associated with diabetes.

“The study provides support for a strategy of assessing cardiovascular risk in people who are overweight, including assessment of blood sugar, cholesterol, and blood pressure levels, all of which can be effectively managed to markedly reduce the risk of future heart attack and stroke,” according to Dr. Storey.
 

More than 400,000 men, women

The researchers enrolled men and women aged 40-69 between 2006 to 2010 who were living in England, Scotland, and Wales. After excluding people with type 1 diabetes or those whose A1c data were missing, the current study included 427,435 people (46% of whom were men).

The participants were classified as having low-normal A1c (< 35 mmol/mol or < 5.5%), normal A1c (35-41 mmol/mol or 5.5%-5.9%), prediabetes (42-47 mmol/mol or 6.0%-6.4%), undiagnosed diabetes (≥ 48 mmol/mol or ≥ 6.5%), or diagnosed type 2 diabetes (medical history and in receipt of glucose-lowering medication).

The researchers determined the incidence of six CVD outcomes during a median 11.8-year follow-up: coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, stroke, and heart failure.

Few participants (5%) had any of these outcomes prior to study enrollment.

During the follow-up, there were 51,288 incident CVD events.

After adjustment for age, compared to having normal A1c, having prediabetes or undiagnosed diabetes was associated with an increased risk of CVD for women and men (hazard ratio [HR], 1.30-1.47).

Among individuals with diagnosed type 2 diabetes, the age-adjusted risk of CVD was greater for women (HR, 2.00) than for men (HR, 1.55).

After further adjustment for clinical and lifestyle factors, especially obesity and antihypertensive or statin use, the risk of CVD decreased and became similar among men and women. The fully adjusted HR for CVD was 1.17 for women and 1.06 for men with diagnosed diabetes.

Compared with having normal A1c, women and men with low-normal A1c were at decreased risk of CVD (HR, 0.86 for both).

The study was funded by Diabetes UK and the British Heart Foundation. Dr. Rentsch and Dr. Storey have disclosed no relevant financial relationships. The disclosures of the other study authors are listed in the original article.
 

A version of this article appeared on Medscape.com.

Men and women with prediabetes, undiagnosed diabetes, and, notably, diagnosed diabetes were at higher risk of incident cardiovascular disease (CVD), whereas those with low-normal A1c were at lower risk of this in a large, 12-year observational study of UK Biobank data.

The results highlight “the need for strategies to reduce risk of CVD across the [glycemic] spectrum,” Christopher T. Rentsch, MPH, PhD, and colleagues wrote in their study, which was published in the The Lancet Regional Health – Europe.

The findings suggest “that excess [CVD] risks in both men and women were largely explained by modifiable factors and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications.

“Addressing these risk factors could reduce sex disparities in [glycemia]-related risks of CVD,” according to the researchers.

After the researchers accounted for age, the absolute rate of CVD events was higher among men than women (16.9 vs. 9.1 events per 1,000 person-years); however, the relative risk was higher among women than men.

Compared with men, women were more likely to have obesity (63% vs. 53%) and were less likely to be using antihypertensive medications (64% vs. 69%) or a statin (71% vs. 75%).

“This is the largest study to date to investigate sex differences in the risk of CVD across the glycemic spectrum,” the researchers noted.
 

“The lower the better”

“We uncovered compelling evidence that for blood sugar levels within the ‘normal’ range, it was a case of ‘the lower the better’ in protecting against heart disease,” Dr. Rentsch, assistant professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, told this news organization.

Compared with people with normal blood glucose levels, those with lower than normal levels were at 10% lower risk of developing any form of heart disease, he noted.

The study findings “support women being proactive in asking about medications like statins and antihypertensives as an option to help lower their [CVD] risk, if clinically appropriate,” Dr. Rentsch added.

“We found that men and women with diagnosed diabetes remained at elevated risk for three types of heart disease – coronary artery disease, stroke, and heart failure – even after accounting for a large number of sociodemographic, lifestyle, and clinical characteristics,” he pointed out.

However, “total cholesterol, family history of CVD, estimated glomerular filtration rate, and C-reactive protein had relatively little impact on explaining the risk of heart disease associated with blood sugar.”

“It is well established that being overweight can lead to higher blood sugar levels as well as higher blood pressure, these being factors that contribute to higher risk of heart attack and stroke,” Robert Storey, DM, professor of cardiology, University of Sheffield (England), told the UK Science Media Centre.

“This very large UK Biobank study,” he said, “shows that the higher heart risk associated with blood sugar can be detected at a very early stage along the path towards the abnormally high blood sugar levels associated with diabetes.

“The study provides support for a strategy of assessing cardiovascular risk in people who are overweight, including assessment of blood sugar, cholesterol, and blood pressure levels, all of which can be effectively managed to markedly reduce the risk of future heart attack and stroke,” according to Dr. Storey.
 

More than 400,000 men, women

The researchers enrolled men and women aged 40-69 between 2006 to 2010 who were living in England, Scotland, and Wales. After excluding people with type 1 diabetes or those whose A1c data were missing, the current study included 427,435 people (46% of whom were men).

The participants were classified as having low-normal A1c (< 35 mmol/mol or < 5.5%), normal A1c (35-41 mmol/mol or 5.5%-5.9%), prediabetes (42-47 mmol/mol or 6.0%-6.4%), undiagnosed diabetes (≥ 48 mmol/mol or ≥ 6.5%), or diagnosed type 2 diabetes (medical history and in receipt of glucose-lowering medication).

The researchers determined the incidence of six CVD outcomes during a median 11.8-year follow-up: coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, stroke, and heart failure.

Few participants (5%) had any of these outcomes prior to study enrollment.

During the follow-up, there were 51,288 incident CVD events.

After adjustment for age, compared to having normal A1c, having prediabetes or undiagnosed diabetes was associated with an increased risk of CVD for women and men (hazard ratio [HR], 1.30-1.47).

Among individuals with diagnosed type 2 diabetes, the age-adjusted risk of CVD was greater for women (HR, 2.00) than for men (HR, 1.55).

After further adjustment for clinical and lifestyle factors, especially obesity and antihypertensive or statin use, the risk of CVD decreased and became similar among men and women. The fully adjusted HR for CVD was 1.17 for women and 1.06 for men with diagnosed diabetes.

Compared with having normal A1c, women and men with low-normal A1c were at decreased risk of CVD (HR, 0.86 for both).

The study was funded by Diabetes UK and the British Heart Foundation. Dr. Rentsch and Dr. Storey have disclosed no relevant financial relationships. The disclosures of the other study authors are listed in the original article.
 

A version of this article appeared on Medscape.com.

Men and women with prediabetes, undiagnosed diabetes, and, notably, diagnosed diabetes were at higher risk of incident cardiovascular disease (CVD), whereas those with low-normal A1c were at lower risk of this in a large, 12-year observational study of UK Biobank data.

The results highlight “the need for strategies to reduce risk of CVD across the [glycemic] spectrum,” Christopher T. Rentsch, MPH, PhD, and colleagues wrote in their study, which was published in the The Lancet Regional Health – Europe.

The findings suggest “that excess [CVD] risks in both men and women were largely explained by modifiable factors and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications.

“Addressing these risk factors could reduce sex disparities in [glycemia]-related risks of CVD,” according to the researchers.

After the researchers accounted for age, the absolute rate of CVD events was higher among men than women (16.9 vs. 9.1 events per 1,000 person-years); however, the relative risk was higher among women than men.

Compared with men, women were more likely to have obesity (63% vs. 53%) and were less likely to be using antihypertensive medications (64% vs. 69%) or a statin (71% vs. 75%).

“This is the largest study to date to investigate sex differences in the risk of CVD across the glycemic spectrum,” the researchers noted.
 

“The lower the better”

“We uncovered compelling evidence that for blood sugar levels within the ‘normal’ range, it was a case of ‘the lower the better’ in protecting against heart disease,” Dr. Rentsch, assistant professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, told this news organization.

Compared with people with normal blood glucose levels, those with lower than normal levels were at 10% lower risk of developing any form of heart disease, he noted.

The study findings “support women being proactive in asking about medications like statins and antihypertensives as an option to help lower their [CVD] risk, if clinically appropriate,” Dr. Rentsch added.

“We found that men and women with diagnosed diabetes remained at elevated risk for three types of heart disease – coronary artery disease, stroke, and heart failure – even after accounting for a large number of sociodemographic, lifestyle, and clinical characteristics,” he pointed out.

However, “total cholesterol, family history of CVD, estimated glomerular filtration rate, and C-reactive protein had relatively little impact on explaining the risk of heart disease associated with blood sugar.”

“It is well established that being overweight can lead to higher blood sugar levels as well as higher blood pressure, these being factors that contribute to higher risk of heart attack and stroke,” Robert Storey, DM, professor of cardiology, University of Sheffield (England), told the UK Science Media Centre.

“This very large UK Biobank study,” he said, “shows that the higher heart risk associated with blood sugar can be detected at a very early stage along the path towards the abnormally high blood sugar levels associated with diabetes.

“The study provides support for a strategy of assessing cardiovascular risk in people who are overweight, including assessment of blood sugar, cholesterol, and blood pressure levels, all of which can be effectively managed to markedly reduce the risk of future heart attack and stroke,” according to Dr. Storey.
 

More than 400,000 men, women

The researchers enrolled men and women aged 40-69 between 2006 to 2010 who were living in England, Scotland, and Wales. After excluding people with type 1 diabetes or those whose A1c data were missing, the current study included 427,435 people (46% of whom were men).

The participants were classified as having low-normal A1c (< 35 mmol/mol or < 5.5%), normal A1c (35-41 mmol/mol or 5.5%-5.9%), prediabetes (42-47 mmol/mol or 6.0%-6.4%), undiagnosed diabetes (≥ 48 mmol/mol or ≥ 6.5%), or diagnosed type 2 diabetes (medical history and in receipt of glucose-lowering medication).

The researchers determined the incidence of six CVD outcomes during a median 11.8-year follow-up: coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, stroke, and heart failure.

Few participants (5%) had any of these outcomes prior to study enrollment.

During the follow-up, there were 51,288 incident CVD events.

After adjustment for age, compared to having normal A1c, having prediabetes or undiagnosed diabetes was associated with an increased risk of CVD for women and men (hazard ratio [HR], 1.30-1.47).

Among individuals with diagnosed type 2 diabetes, the age-adjusted risk of CVD was greater for women (HR, 2.00) than for men (HR, 1.55).

After further adjustment for clinical and lifestyle factors, especially obesity and antihypertensive or statin use, the risk of CVD decreased and became similar among men and women. The fully adjusted HR for CVD was 1.17 for women and 1.06 for men with diagnosed diabetes.

Compared with having normal A1c, women and men with low-normal A1c were at decreased risk of CVD (HR, 0.86 for both).

The study was funded by Diabetes UK and the British Heart Foundation. Dr. Rentsch and Dr. Storey have disclosed no relevant financial relationships. The disclosures of the other study authors are listed in the original article.
 

A version of this article appeared on Medscape.com.

Only a small fraction of older adults in the early stages of Alzheimer’s disease (AD) meet eligibility criteria to receive treatment with newly approved antiamyloid drugs, largely because of the presence of medical conditions or neuroimaging findings, new research shows. 

Applying the clinical trial criteria, only about 8%-17% of amyloid-positive individuals with early AD would be eligible for lecanemab (Leqembi), and even fewer, 5%-9%, would be eligible for aducanumab (Aduhelm), the researchers found.

This study highlights the “limited suitability” of most adults with mild cognitive impairment (MCI) or mild dementia with elevated brain amyloid for treatment with these anti–beta amyloid monoclonal antibodies, write Maria Vassilaki, MD, PhD, and colleagues with Mayo Clinic, Rochester, Minn.

The study was published online in Neurology 

The authors of an accompanying editorial write that this study “provides an important estimate of treatment eligibility for amyloid-lowering monoclonal antibodies for early AD to help health systems make realistic plans for providing these treatments.”
 

More real-world data needed

Dr. Vassilaki and colleagues applied eligibility criteria for lecanemab and aducanumab to 237 older adults with MCI or mild dementia and increased brain amyloid burden from the Mayo Clinic Study of Aging (MCSA). Their mean age was 80.9 years, 55% were men, and most were White. 

After applying lecanemab’s inclusion criteria, less than half of the study population was eligible to receive treatment (112 of 237, or 47%). 

A total of 21 people were excluded because of a body mass index less than 17 or greater than or equal to 35; 48 due to a Clinical Dementia Rating (CDR) global score other than 0.5 or 1.0; 46 because they did not meet WMS-R Logical Memory II scores for age; 8 because of a Mini Mental State Examination (MMSE) score outside the bounds of 22-30; and two because of a CDR memory score less than 0.5. 

Applying lecanemab’s exclusion criteria further narrowed the number of eligible participants from 112 to 19 (8% of 237). 

Notable exclusions included cardiopulmonary contraindications, central nervous system–related exclusions such as brain cancer, Parkinson’s disease, epilepsy or brain injury, imaging findings, and history of cancer. 

The results were similar for aducanumab, with 104 of the 237 participants (44%) meeting the trial’s inclusion criteria. Applying aducanumab’s exclusion criteria further reduced the number of eligible participants to 12 (5% of 237).

A sensitivity analysis including participants with MCI, without CDR global, MMSE, or WMS-R Logical Memory II score restrictions, resulted in a somewhat higher percentage of eligible participants (17.4% for lecanemab and 8.9% for aducanumab). 
 

Shared decision-making

“Clinicians and health systems should be aware that by applying the clinical trial criteria, a smaller percentage might be eligible for these treatments than originally anticipated,” Dr. Vassilaki told this news organization. To help clinicians, there are published recommendations for the appropriate use of these treatments, she noted. 

Given that clinical trial participants are typically healthier than the general population, Dr. Vassilaki said that research is needed to examine the safety and efficacy of antiamyloid therapies in larger, more diverse populations as well as in less healthy populations, before these therapies may be more widely available to people with AD. 

“We can take advantage of the postmarketing surveillance of side effects, and also enrollment of patients receiving these treatments to registries could provide us with data useful for any necessary adjustment to drug use,” Dr. Vassilaki told this news organization. 
 

‘Sharp focus’

This study “brings the issue of eligibility for amyloid-lowering antibody treatment into sharp focus,” Matthew Howe, MD, PhD, with Butler Hospital Memory & Aging Program, Providence, R.I., and colleagues note in their editorial. 

“The results underscore the importance of careful patient selection to help identify patients most likely to benefit from treatment and exclude those at risk for serious outcomes,” they write. 

They also write that appropriate use recommendations for lecanemab and aducanumab “will be revisited as more real-world data emerge, especially about safety.”

For now, clinicians “must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” they add. 

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation and the Schuler Foundation. Dr. Vassilaki has consulted for F. Hoffmann-La Roche and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no conflicts of interest. 

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

Only a small fraction of older adults in the early stages of Alzheimer’s disease (AD) meet eligibility criteria to receive treatment with newly approved antiamyloid drugs, largely because of the presence of medical conditions or neuroimaging findings, new research shows. 

Applying the clinical trial criteria, only about 8%-17% of amyloid-positive individuals with early AD would be eligible for lecanemab (Leqembi), and even fewer, 5%-9%, would be eligible for aducanumab (Aduhelm), the researchers found.

This study highlights the “limited suitability” of most adults with mild cognitive impairment (MCI) or mild dementia with elevated brain amyloid for treatment with these anti–beta amyloid monoclonal antibodies, write Maria Vassilaki, MD, PhD, and colleagues with Mayo Clinic, Rochester, Minn.

The study was published online in Neurology 

The authors of an accompanying editorial write that this study “provides an important estimate of treatment eligibility for amyloid-lowering monoclonal antibodies for early AD to help health systems make realistic plans for providing these treatments.”
 

More real-world data needed

Dr. Vassilaki and colleagues applied eligibility criteria for lecanemab and aducanumab to 237 older adults with MCI or mild dementia and increased brain amyloid burden from the Mayo Clinic Study of Aging (MCSA). Their mean age was 80.9 years, 55% were men, and most were White. 

After applying lecanemab’s inclusion criteria, less than half of the study population was eligible to receive treatment (112 of 237, or 47%). 

A total of 21 people were excluded because of a body mass index less than 17 or greater than or equal to 35; 48 due to a Clinical Dementia Rating (CDR) global score other than 0.5 or 1.0; 46 because they did not meet WMS-R Logical Memory II scores for age; 8 because of a Mini Mental State Examination (MMSE) score outside the bounds of 22-30; and two because of a CDR memory score less than 0.5. 

Applying lecanemab’s exclusion criteria further narrowed the number of eligible participants from 112 to 19 (8% of 237). 

Notable exclusions included cardiopulmonary contraindications, central nervous system–related exclusions such as brain cancer, Parkinson’s disease, epilepsy or brain injury, imaging findings, and history of cancer. 

The results were similar for aducanumab, with 104 of the 237 participants (44%) meeting the trial’s inclusion criteria. Applying aducanumab’s exclusion criteria further reduced the number of eligible participants to 12 (5% of 237).

A sensitivity analysis including participants with MCI, without CDR global, MMSE, or WMS-R Logical Memory II score restrictions, resulted in a somewhat higher percentage of eligible participants (17.4% for lecanemab and 8.9% for aducanumab). 
 

Shared decision-making

“Clinicians and health systems should be aware that by applying the clinical trial criteria, a smaller percentage might be eligible for these treatments than originally anticipated,” Dr. Vassilaki told this news organization. To help clinicians, there are published recommendations for the appropriate use of these treatments, she noted. 

Given that clinical trial participants are typically healthier than the general population, Dr. Vassilaki said that research is needed to examine the safety and efficacy of antiamyloid therapies in larger, more diverse populations as well as in less healthy populations, before these therapies may be more widely available to people with AD. 

“We can take advantage of the postmarketing surveillance of side effects, and also enrollment of patients receiving these treatments to registries could provide us with data useful for any necessary adjustment to drug use,” Dr. Vassilaki told this news organization. 
 

‘Sharp focus’

This study “brings the issue of eligibility for amyloid-lowering antibody treatment into sharp focus,” Matthew Howe, MD, PhD, with Butler Hospital Memory & Aging Program, Providence, R.I., and colleagues note in their editorial. 

“The results underscore the importance of careful patient selection to help identify patients most likely to benefit from treatment and exclude those at risk for serious outcomes,” they write. 

They also write that appropriate use recommendations for lecanemab and aducanumab “will be revisited as more real-world data emerge, especially about safety.”

For now, clinicians “must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” they add. 

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation and the Schuler Foundation. Dr. Vassilaki has consulted for F. Hoffmann-La Roche and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no conflicts of interest. 

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

Only a small fraction of older adults in the early stages of Alzheimer’s disease (AD) meet eligibility criteria to receive treatment with newly approved antiamyloid drugs, largely because of the presence of medical conditions or neuroimaging findings, new research shows. 

Applying the clinical trial criteria, only about 8%-17% of amyloid-positive individuals with early AD would be eligible for lecanemab (Leqembi), and even fewer, 5%-9%, would be eligible for aducanumab (Aduhelm), the researchers found.

This study highlights the “limited suitability” of most adults with mild cognitive impairment (MCI) or mild dementia with elevated brain amyloid for treatment with these anti–beta amyloid monoclonal antibodies, write Maria Vassilaki, MD, PhD, and colleagues with Mayo Clinic, Rochester, Minn.

The study was published online in Neurology 

The authors of an accompanying editorial write that this study “provides an important estimate of treatment eligibility for amyloid-lowering monoclonal antibodies for early AD to help health systems make realistic plans for providing these treatments.”
 

More real-world data needed

Dr. Vassilaki and colleagues applied eligibility criteria for lecanemab and aducanumab to 237 older adults with MCI or mild dementia and increased brain amyloid burden from the Mayo Clinic Study of Aging (MCSA). Their mean age was 80.9 years, 55% were men, and most were White. 

After applying lecanemab’s inclusion criteria, less than half of the study population was eligible to receive treatment (112 of 237, or 47%). 

A total of 21 people were excluded because of a body mass index less than 17 or greater than or equal to 35; 48 due to a Clinical Dementia Rating (CDR) global score other than 0.5 or 1.0; 46 because they did not meet WMS-R Logical Memory II scores for age; 8 because of a Mini Mental State Examination (MMSE) score outside the bounds of 22-30; and two because of a CDR memory score less than 0.5. 

Applying lecanemab’s exclusion criteria further narrowed the number of eligible participants from 112 to 19 (8% of 237). 

Notable exclusions included cardiopulmonary contraindications, central nervous system–related exclusions such as brain cancer, Parkinson’s disease, epilepsy or brain injury, imaging findings, and history of cancer. 

The results were similar for aducanumab, with 104 of the 237 participants (44%) meeting the trial’s inclusion criteria. Applying aducanumab’s exclusion criteria further reduced the number of eligible participants to 12 (5% of 237).

A sensitivity analysis including participants with MCI, without CDR global, MMSE, or WMS-R Logical Memory II score restrictions, resulted in a somewhat higher percentage of eligible participants (17.4% for lecanemab and 8.9% for aducanumab). 
 

Shared decision-making

“Clinicians and health systems should be aware that by applying the clinical trial criteria, a smaller percentage might be eligible for these treatments than originally anticipated,” Dr. Vassilaki told this news organization. To help clinicians, there are published recommendations for the appropriate use of these treatments, she noted. 

Given that clinical trial participants are typically healthier than the general population, Dr. Vassilaki said that research is needed to examine the safety and efficacy of antiamyloid therapies in larger, more diverse populations as well as in less healthy populations, before these therapies may be more widely available to people with AD. 

“We can take advantage of the postmarketing surveillance of side effects, and also enrollment of patients receiving these treatments to registries could provide us with data useful for any necessary adjustment to drug use,” Dr. Vassilaki told this news organization. 
 

‘Sharp focus’

This study “brings the issue of eligibility for amyloid-lowering antibody treatment into sharp focus,” Matthew Howe, MD, PhD, with Butler Hospital Memory & Aging Program, Providence, R.I., and colleagues note in their editorial. 

“The results underscore the importance of careful patient selection to help identify patients most likely to benefit from treatment and exclude those at risk for serious outcomes,” they write. 

They also write that appropriate use recommendations for lecanemab and aducanumab “will be revisited as more real-world data emerge, especially about safety.”

For now, clinicians “must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” they add. 

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation and the Schuler Foundation. Dr. Vassilaki has consulted for F. Hoffmann-La Roche and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no conflicts of interest. 

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

PARIS – “We need to develop new therapies to treat addiction because of the related cost to society, which is extremely high,” said Bruno Roméo, MD, psychiatrist and addiction specialist at Paul Brousse Hospital in Villejuif, France, at the Paris-based Neuroscience, Psychiatry and Neurology Conference. Dr. Roméo spoke about the current place of psychedelics in the treatment of addiction.

“Smoking and alcohol consumption are the two main preventable causes of death in France,” he said. “Current management strategies for these addictions rarely involve pharmacological therapies, which are not very effective, in any case. We have massive relapse rates, signaling the need to develop other treatments, like psychedelic drugs.”

But what data are available on the efficacy of psychedelics in treating addiction?

Alcohol use disorder

There are few data concerning the role of psychedelics in the treatment of alcohol use disorder, but one controlled, randomized trial evaluated the efficacy of psilocybin. That trial was published in JAMA Psychiatry in 2022.

That study included 95 patients with alcohol use disorder; 49 were treated with psilocybin, and 46 were treated with diphenhydramine.

An initial medication session of psilocybin was given in week 4, then another in week 8 at a higher dose. The number of drinking days, the number of heavy drinking days, and the number of drinks consumed between weeks 32 and 36 were assessed.

The investigators showed that, after two sessions with psilocybin, there was a significant reduction in the number of heavy drinking days. In the control group, between weeks 5 and 36, 20% of days involved heavy drinking, whereas in the psilocybin group, 10% of days involved heavy drinking.

There was also a significant and rapid reduction in the number of drinking days, and this was maintained over time. Between weeks 5 and 36, just over 40% of days were reported as drinking days in the control group versus slightly more than 30% in the psilocybin group.

Similarly, the number of glasses per day was drastically reduced after taking psilocybin, and the effect occurred extremely quickly. Consumption went from six drinks to less than one drink between weeks 5 and 8. Overall, between weeks 5 and 36, the number of drinks consumed per day was more than two in the placebo group and more than one in the psilocybin group.

“Psilocybin was seen as having potential efficacy in treating alcohol use disorder. But we must tread carefully with these results; the profile of the patients enrolled in this study is different to that of the patients we regularly see in our addiction clinics. The patients enrolled in the study reported less than 60% of days as heavy drinking days,” said Dr. Romeo.
 

Candidates for psilocybin

According to a retrospective survey of 160 respondents that was conducted online at Paul Brousse Hospital, patients with the most severe cases of alcohol use disorder who have the most mystical psychedelic experiences seem to respond best to psilocybin and to reduce their alcohol use. It also appears that patients whose alcohol use decreased the most had lower psychological flexibility on enrollment in the study. (Psychological flexibility is the ability to adapt to change and to cope with positive and negative experiences in real time without being fazed or trying to flee from the situation.) “It’s as if they had a broader capacity for change, and psychedelics helped them more,” said Dr. Roméo.

Smoking cessation

“There are even fewer studies for smoking,” said Dr. Roméo. In a pilot study with 15 patients, the researchers gave two or three doses of psilocybin at 20-30 mg in combination with cognitive-behavioral therapy one session per week for 10 weeks. Thereafter, patients were assessed three times: after 6 months, 12 months, and 30 months.

The results showed a significant reduction in smoking. Patients went from smoking more than 15 cigarettes per day to smoking one to two cigarettes per day before going back up to six cigarettes daily.

Regarding abstinence rates, 12 of 15 patients had stopped smoking after 6 months, 8 of 15 after 1 year, and 7 of 15 after 30 months. “This study produced some interesting results, although caution must obviously be taken due to the very low number of patients enrolled,” said Dr. Roméo.

As is the case for alcohol, a retrospective survey conducted via questionnaire at Paul Brousse Hospital showed that the patients who smoked the most and who had the most mystical psychedelic experiences seemed to respond best to psilocybin and therefore to reduce their tobacco use. It also seemed to be the case that patients who reduced tobacco use the most had lower psychological flexibility on enrollment in the study.
 

Constraints on psychedelics

“Psychedelics are somewhat effective in treating addiction, but there are various limitations to their use,” said Dr. Roméo.

One of those limitations is societal. Laurence Bézo, MD, of the addiction services clinic at Paul Brousse Hospital, asked doctors to respond to a questionnaire to determine what they thought about psychedelics. To date, 407 have responded, including 280 general practitioners, 50 addiction specialists, and 50 specialist physicians. Overall, 50% think that psychedelics have no therapeutic potential. Three of five doctors also said that psychedelics are dangerous. Just over half thought that their use is associated with a severe risk of aggression aimed at oneself and toward others. Likewise, half think that the risk of dependency is very high and that there is a risk of co-occurring psychiatric disorders. “From the pool of physicians queried, the consensus is that psychedelics are pretty dangerous. People also seem to frown upon prescribing psychedelics in France,” said Dr. Roméo.

Participants went as far as to classify psychedelics as some of the most dangerous drugs out there.

Using a 7-point scale, they classified psychedelics below heroin and cocaine in terms of dangerousness. They are deemed much more harmful than alcohol, tobacco, and cannabis.

“A survey of the public carried out several years ago by leading French market research group IFOP had the exact same findings. Nevertheless, a number of studies have set out to determine how dangerous psychedelics are, and their findings point to this class of drugs as being among the least harmful for the individual patient and those around them. On the contrary, alcohol, heroin, crack cocaine (or even cocaine),methamphetamine, and tobacco were shown to be the most harmful. Additionally, psychedelics have a very low risk of dependency and the lowest risk of lethality. There is complete dissonance between what recent studies show us and what society, and some doctors, think,” said Dr. Roméo.

Besides these assumptions, another constraint to the use of psychedelics relates to methods adopted in related clinical studies. “Due to the effect psychedelics have, in the trials conducted, 9 participants and 9 doctors out of 10 are aware of what they have taken or given, respectively. This is a very important limitation. Nowadays, researchers don’t know how to conduct accurate double-blind studies,” said Dr. Roméo.

In sum, for psychiatrists, psychedelics are promising in addiction therapy, but health care professionals, public authorities, and society as a whole must be better informed about their use, and received ideas must be dispelled.

“The findings need to be replicated, but overall, psychedelics are really quite promising in treating both alcohol and tobacco use disorder. They are generally well tolerated with few serious side effects. There is no deterioration in patients with psychiatric conditions while they are taking psychedelics. And if persistent symptoms of psychosis do occur, which is extremely rare, it’s probably because there are preexisting underlying issues at play. We also don’t see increased blood pressure or any other serious physical anomalies. In a supervised setting, as is the case with studies involving psychotherapeutic support, we can no longer say, in this day and age, that psychedelics are harmful,” said Dr. Roméo.

Dr. Roméo reported no conflicts of interest regarding the content of this article.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

PARIS – “We need to develop new therapies to treat addiction because of the related cost to society, which is extremely high,” said Bruno Roméo, MD, psychiatrist and addiction specialist at Paul Brousse Hospital in Villejuif, France, at the Paris-based Neuroscience, Psychiatry and Neurology Conference. Dr. Roméo spoke about the current place of psychedelics in the treatment of addiction.

“Smoking and alcohol consumption are the two main preventable causes of death in France,” he said. “Current management strategies for these addictions rarely involve pharmacological therapies, which are not very effective, in any case. We have massive relapse rates, signaling the need to develop other treatments, like psychedelic drugs.”

But what data are available on the efficacy of psychedelics in treating addiction?

Alcohol use disorder

There are few data concerning the role of psychedelics in the treatment of alcohol use disorder, but one controlled, randomized trial evaluated the efficacy of psilocybin. That trial was published in JAMA Psychiatry in 2022.

That study included 95 patients with alcohol use disorder; 49 were treated with psilocybin, and 46 were treated with diphenhydramine.

An initial medication session of psilocybin was given in week 4, then another in week 8 at a higher dose. The number of drinking days, the number of heavy drinking days, and the number of drinks consumed between weeks 32 and 36 were assessed.

The investigators showed that, after two sessions with psilocybin, there was a significant reduction in the number of heavy drinking days. In the control group, between weeks 5 and 36, 20% of days involved heavy drinking, whereas in the psilocybin group, 10% of days involved heavy drinking.

There was also a significant and rapid reduction in the number of drinking days, and this was maintained over time. Between weeks 5 and 36, just over 40% of days were reported as drinking days in the control group versus slightly more than 30% in the psilocybin group.

Similarly, the number of glasses per day was drastically reduced after taking psilocybin, and the effect occurred extremely quickly. Consumption went from six drinks to less than one drink between weeks 5 and 8. Overall, between weeks 5 and 36, the number of drinks consumed per day was more than two in the placebo group and more than one in the psilocybin group.

“Psilocybin was seen as having potential efficacy in treating alcohol use disorder. But we must tread carefully with these results; the profile of the patients enrolled in this study is different to that of the patients we regularly see in our addiction clinics. The patients enrolled in the study reported less than 60% of days as heavy drinking days,” said Dr. Romeo.
 

Candidates for psilocybin

According to a retrospective survey of 160 respondents that was conducted online at Paul Brousse Hospital, patients with the most severe cases of alcohol use disorder who have the most mystical psychedelic experiences seem to respond best to psilocybin and to reduce their alcohol use. It also appears that patients whose alcohol use decreased the most had lower psychological flexibility on enrollment in the study. (Psychological flexibility is the ability to adapt to change and to cope with positive and negative experiences in real time without being fazed or trying to flee from the situation.) “It’s as if they had a broader capacity for change, and psychedelics helped them more,” said Dr. Roméo.

Smoking cessation

“There are even fewer studies for smoking,” said Dr. Roméo. In a pilot study with 15 patients, the researchers gave two or three doses of psilocybin at 20-30 mg in combination with cognitive-behavioral therapy one session per week for 10 weeks. Thereafter, patients were assessed three times: after 6 months, 12 months, and 30 months.

The results showed a significant reduction in smoking. Patients went from smoking more than 15 cigarettes per day to smoking one to two cigarettes per day before going back up to six cigarettes daily.

Regarding abstinence rates, 12 of 15 patients had stopped smoking after 6 months, 8 of 15 after 1 year, and 7 of 15 after 30 months. “This study produced some interesting results, although caution must obviously be taken due to the very low number of patients enrolled,” said Dr. Roméo.

As is the case for alcohol, a retrospective survey conducted via questionnaire at Paul Brousse Hospital showed that the patients who smoked the most and who had the most mystical psychedelic experiences seemed to respond best to psilocybin and therefore to reduce their tobacco use. It also seemed to be the case that patients who reduced tobacco use the most had lower psychological flexibility on enrollment in the study.
 

Constraints on psychedelics

“Psychedelics are somewhat effective in treating addiction, but there are various limitations to their use,” said Dr. Roméo.

One of those limitations is societal. Laurence Bézo, MD, of the addiction services clinic at Paul Brousse Hospital, asked doctors to respond to a questionnaire to determine what they thought about psychedelics. To date, 407 have responded, including 280 general practitioners, 50 addiction specialists, and 50 specialist physicians. Overall, 50% think that psychedelics have no therapeutic potential. Three of five doctors also said that psychedelics are dangerous. Just over half thought that their use is associated with a severe risk of aggression aimed at oneself and toward others. Likewise, half think that the risk of dependency is very high and that there is a risk of co-occurring psychiatric disorders. “From the pool of physicians queried, the consensus is that psychedelics are pretty dangerous. People also seem to frown upon prescribing psychedelics in France,” said Dr. Roméo.

Participants went as far as to classify psychedelics as some of the most dangerous drugs out there.

Using a 7-point scale, they classified psychedelics below heroin and cocaine in terms of dangerousness. They are deemed much more harmful than alcohol, tobacco, and cannabis.

“A survey of the public carried out several years ago by leading French market research group IFOP had the exact same findings. Nevertheless, a number of studies have set out to determine how dangerous psychedelics are, and their findings point to this class of drugs as being among the least harmful for the individual patient and those around them. On the contrary, alcohol, heroin, crack cocaine (or even cocaine),methamphetamine, and tobacco were shown to be the most harmful. Additionally, psychedelics have a very low risk of dependency and the lowest risk of lethality. There is complete dissonance between what recent studies show us and what society, and some doctors, think,” said Dr. Roméo.

Besides these assumptions, another constraint to the use of psychedelics relates to methods adopted in related clinical studies. “Due to the effect psychedelics have, in the trials conducted, 9 participants and 9 doctors out of 10 are aware of what they have taken or given, respectively. This is a very important limitation. Nowadays, researchers don’t know how to conduct accurate double-blind studies,” said Dr. Roméo.

In sum, for psychiatrists, psychedelics are promising in addiction therapy, but health care professionals, public authorities, and society as a whole must be better informed about their use, and received ideas must be dispelled.

“The findings need to be replicated, but overall, psychedelics are really quite promising in treating both alcohol and tobacco use disorder. They are generally well tolerated with few serious side effects. There is no deterioration in patients with psychiatric conditions while they are taking psychedelics. And if persistent symptoms of psychosis do occur, which is extremely rare, it’s probably because there are preexisting underlying issues at play. We also don’t see increased blood pressure or any other serious physical anomalies. In a supervised setting, as is the case with studies involving psychotherapeutic support, we can no longer say, in this day and age, that psychedelics are harmful,” said Dr. Roméo.

Dr. Roméo reported no conflicts of interest regarding the content of this article.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

PARIS – “We need to develop new therapies to treat addiction because of the related cost to society, which is extremely high,” said Bruno Roméo, MD, psychiatrist and addiction specialist at Paul Brousse Hospital in Villejuif, France, at the Paris-based Neuroscience, Psychiatry and Neurology Conference. Dr. Roméo spoke about the current place of psychedelics in the treatment of addiction.

“Smoking and alcohol consumption are the two main preventable causes of death in France,” he said. “Current management strategies for these addictions rarely involve pharmacological therapies, which are not very effective, in any case. We have massive relapse rates, signaling the need to develop other treatments, like psychedelic drugs.”

But what data are available on the efficacy of psychedelics in treating addiction?

Alcohol use disorder

There are few data concerning the role of psychedelics in the treatment of alcohol use disorder, but one controlled, randomized trial evaluated the efficacy of psilocybin. That trial was published in JAMA Psychiatry in 2022.

That study included 95 patients with alcohol use disorder; 49 were treated with psilocybin, and 46 were treated with diphenhydramine.

An initial medication session of psilocybin was given in week 4, then another in week 8 at a higher dose. The number of drinking days, the number of heavy drinking days, and the number of drinks consumed between weeks 32 and 36 were assessed.

The investigators showed that, after two sessions with psilocybin, there was a significant reduction in the number of heavy drinking days. In the control group, between weeks 5 and 36, 20% of days involved heavy drinking, whereas in the psilocybin group, 10% of days involved heavy drinking.

There was also a significant and rapid reduction in the number of drinking days, and this was maintained over time. Between weeks 5 and 36, just over 40% of days were reported as drinking days in the control group versus slightly more than 30% in the psilocybin group.

Similarly, the number of glasses per day was drastically reduced after taking psilocybin, and the effect occurred extremely quickly. Consumption went from six drinks to less than one drink between weeks 5 and 8. Overall, between weeks 5 and 36, the number of drinks consumed per day was more than two in the placebo group and more than one in the psilocybin group.

“Psilocybin was seen as having potential efficacy in treating alcohol use disorder. But we must tread carefully with these results; the profile of the patients enrolled in this study is different to that of the patients we regularly see in our addiction clinics. The patients enrolled in the study reported less than 60% of days as heavy drinking days,” said Dr. Romeo.
 

Candidates for psilocybin

According to a retrospective survey of 160 respondents that was conducted online at Paul Brousse Hospital, patients with the most severe cases of alcohol use disorder who have the most mystical psychedelic experiences seem to respond best to psilocybin and to reduce their alcohol use. It also appears that patients whose alcohol use decreased the most had lower psychological flexibility on enrollment in the study. (Psychological flexibility is the ability to adapt to change and to cope with positive and negative experiences in real time without being fazed or trying to flee from the situation.) “It’s as if they had a broader capacity for change, and psychedelics helped them more,” said Dr. Roméo.

Smoking cessation

“There are even fewer studies for smoking,” said Dr. Roméo. In a pilot study with 15 patients, the researchers gave two or three doses of psilocybin at 20-30 mg in combination with cognitive-behavioral therapy one session per week for 10 weeks. Thereafter, patients were assessed three times: after 6 months, 12 months, and 30 months.

The results showed a significant reduction in smoking. Patients went from smoking more than 15 cigarettes per day to smoking one to two cigarettes per day before going back up to six cigarettes daily.

Regarding abstinence rates, 12 of 15 patients had stopped smoking after 6 months, 8 of 15 after 1 year, and 7 of 15 after 30 months. “This study produced some interesting results, although caution must obviously be taken due to the very low number of patients enrolled,” said Dr. Roméo.

As is the case for alcohol, a retrospective survey conducted via questionnaire at Paul Brousse Hospital showed that the patients who smoked the most and who had the most mystical psychedelic experiences seemed to respond best to psilocybin and therefore to reduce their tobacco use. It also seemed to be the case that patients who reduced tobacco use the most had lower psychological flexibility on enrollment in the study.
 

Constraints on psychedelics

“Psychedelics are somewhat effective in treating addiction, but there are various limitations to their use,” said Dr. Roméo.

One of those limitations is societal. Laurence Bézo, MD, of the addiction services clinic at Paul Brousse Hospital, asked doctors to respond to a questionnaire to determine what they thought about psychedelics. To date, 407 have responded, including 280 general practitioners, 50 addiction specialists, and 50 specialist physicians. Overall, 50% think that psychedelics have no therapeutic potential. Three of five doctors also said that psychedelics are dangerous. Just over half thought that their use is associated with a severe risk of aggression aimed at oneself and toward others. Likewise, half think that the risk of dependency is very high and that there is a risk of co-occurring psychiatric disorders. “From the pool of physicians queried, the consensus is that psychedelics are pretty dangerous. People also seem to frown upon prescribing psychedelics in France,” said Dr. Roméo.

Participants went as far as to classify psychedelics as some of the most dangerous drugs out there.

Using a 7-point scale, they classified psychedelics below heroin and cocaine in terms of dangerousness. They are deemed much more harmful than alcohol, tobacco, and cannabis.

“A survey of the public carried out several years ago by leading French market research group IFOP had the exact same findings. Nevertheless, a number of studies have set out to determine how dangerous psychedelics are, and their findings point to this class of drugs as being among the least harmful for the individual patient and those around them. On the contrary, alcohol, heroin, crack cocaine (or even cocaine),methamphetamine, and tobacco were shown to be the most harmful. Additionally, psychedelics have a very low risk of dependency and the lowest risk of lethality. There is complete dissonance between what recent studies show us and what society, and some doctors, think,” said Dr. Roméo.

Besides these assumptions, another constraint to the use of psychedelics relates to methods adopted in related clinical studies. “Due to the effect psychedelics have, in the trials conducted, 9 participants and 9 doctors out of 10 are aware of what they have taken or given, respectively. This is a very important limitation. Nowadays, researchers don’t know how to conduct accurate double-blind studies,” said Dr. Roméo.

In sum, for psychiatrists, psychedelics are promising in addiction therapy, but health care professionals, public authorities, and society as a whole must be better informed about their use, and received ideas must be dispelled.

“The findings need to be replicated, but overall, psychedelics are really quite promising in treating both alcohol and tobacco use disorder. They are generally well tolerated with few serious side effects. There is no deterioration in patients with psychiatric conditions while they are taking psychedelics. And if persistent symptoms of psychosis do occur, which is extremely rare, it’s probably because there are preexisting underlying issues at play. We also don’t see increased blood pressure or any other serious physical anomalies. In a supervised setting, as is the case with studies involving psychotherapeutic support, we can no longer say, in this day and age, that psychedelics are harmful,” said Dr. Roméo.

Dr. Roméo reported no conflicts of interest regarding the content of this article.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

At the week follow-up, the lesions were unchanged and the swelling on the left lateral eyebrow was worsening. A biopsy of the yellow lesion on the back and one of the scaly papules on the abdomen was performed. A fungal and bacterial cultures were also ordered.

He was referred to ophthalmology for evaluation of the eyelid swelling and an ultrasound was requested.

The skin biopsy showed a clonal proliferation of reniform histiocytes with eosinophils within the dermis. The cells were positive for S100, CD207 (langerin), and CD1a and negative for pancytokeratin and Melan-A, supportive of the diagnosis of Langerhans cell histiocytosis (LCH).
 

Diagnosis

The patient was admitted to the hospital, where a skeletal survey was performed, which showed an asymmetric lucency involving the left frontal calvarium extending to the superior lateral orbital rim. The brain MRI demonstrated a destructive avidly enhancing soft-tissue process which involved the superior left orbital rim likely with some degree of intracranial extension. This lesion exerts mass effect upon surrounding structures to the left ocular globe. With the skin and skeletal findings, the patient was diagnosed with LCH. His blood count was significant for thrombocytopenia. His liver and kidney function were normal. His electrolytes were also with in normal range. He was started on chemotherapy with vinblastine and systemic corticosteroids with resolution of the rash and decrease on the size of the lesion on the orbit within a few weeks.

Infantile LCH is a rare neoplastic disorder of hematopoietic myeloid precursor cells caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, particularly BRAF-V600E mutation. White male children are mostly affected, with a peak incidence of 1-3 years of age. Nine out of 10 children with cutaneous involvement also have multisystemic disease, such as the case of our patient. LCH is classified as single or multisystem organ disease. Two-thirds of the cases present with single system involvement. Organs most commonly affected include the bone (the skull being the most commonly affected), skin, and high-risk organs like the liver, spleen, and bone marrow, and less commonly the lungs, lymph nodes, and central nervous system. Some patients can present with fever, lethargy, and weight loss. None were noted in our patient.

Skin findings of LCH can have multiple morphologies and presentations and often described as a big mimicker. In young infants like our patient, the seborrheic dermatitis–mimicking type is often seen. In other cases, the skin lesions can appear eczematous, petechial, with scabbing, crusting, or purpura. Xanthoma-like lesions, like that one our patient had in the back, have also been described. Resistant diaper dermatitis and cradle cap should prompt the clinician to think about LCH. Lesions can be so varied that can present with hypopigmentation (vitiligo like), hyperpigmentation, varicella-like papulo-pustules, and red blue nodules within others. Oral mucosa and nail involvement can also occur.

Bone involvement can present as soft-tissue mass with swelling and pain as it occur in our patient.

Endocrinopathies have been described in patients with LCH including diabetes insipidus, growth hormone deficiency, and less likely thyroid disease.
 

Multidisciplinary care

The diagnosis of LCH in infants necessitates a combination of clinical, radiological, and histopathologic findings. In infants, cutaneous involvement is a frequent initial presentation, with characteristic lesions that are often misdiagnosed as other dermatologic conditions. Timely recognition of these lesions and appropriate skin biopsies for histological examination are essential steps in achieving an accurate diagnosis.

Radiological imaging, including x-rays, CT, and MRI, plays a crucial role in assessing the extent of involvement.

The management of LCH in infants requires a well-coordinated multidisciplinary approach involving pediatric oncologists, dermatologists, radiologists, orthopedic surgeons, and other relevant specialists. Treatment strategies vary depending on the extent of disease involvement and the presence of risk factors. In localized cases, observation with close monitoring may be considered, as some cases of LCH in infants may undergo spontaneous regression. However, cases with severe symptoms, extensive organ involvement, or high-risk features may require systemic therapies.

Chemotherapy agents, including vinblastine and prednisone have been utilized in the treatment of infantile LCH with varying success. The selection of treatment regimens should be tailored to each individual case, considering disease severity, potential toxicities, and long-term effects. In cases of bone lesions causing significant deformities or functional impairment, surgical intervention may be necessary. Skin only disease can be treated with topical corticosteroids.
 

Prognosis

Survival rates in patients with single-organ involvement without risk-organ involvement is close to 100% and with risk-organ involvement of 98% at 5 years.

Long-term follow-up is essential for infants diagnosed with LCH, as recurrence and late effects can occur even after successful treatment. Continued monitoring allows for the timely detection of relapses or the development of secondary complications.

Infants thought to have common skin conditions like eczema, seborrheic dermatitis, or diaper dermatitis not responding to treatment should be referred to pediatric dermatology for evaluation to rule out the possibility of LCH.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1035-44.

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1047-56.

Leung AKC et al. World J Pediatr. 2019 Dec;15(6):536-45.

At the week follow-up, the lesions were unchanged and the swelling on the left lateral eyebrow was worsening. A biopsy of the yellow lesion on the back and one of the scaly papules on the abdomen was performed. A fungal and bacterial cultures were also ordered.

He was referred to ophthalmology for evaluation of the eyelid swelling and an ultrasound was requested.

The skin biopsy showed a clonal proliferation of reniform histiocytes with eosinophils within the dermis. The cells were positive for S100, CD207 (langerin), and CD1a and negative for pancytokeratin and Melan-A, supportive of the diagnosis of Langerhans cell histiocytosis (LCH).
 

Diagnosis

The patient was admitted to the hospital, where a skeletal survey was performed, which showed an asymmetric lucency involving the left frontal calvarium extending to the superior lateral orbital rim. The brain MRI demonstrated a destructive avidly enhancing soft-tissue process which involved the superior left orbital rim likely with some degree of intracranial extension. This lesion exerts mass effect upon surrounding structures to the left ocular globe. With the skin and skeletal findings, the patient was diagnosed with LCH. His blood count was significant for thrombocytopenia. His liver and kidney function were normal. His electrolytes were also with in normal range. He was started on chemotherapy with vinblastine and systemic corticosteroids with resolution of the rash and decrease on the size of the lesion on the orbit within a few weeks.

Infantile LCH is a rare neoplastic disorder of hematopoietic myeloid precursor cells caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, particularly BRAF-V600E mutation. White male children are mostly affected, with a peak incidence of 1-3 years of age. Nine out of 10 children with cutaneous involvement also have multisystemic disease, such as the case of our patient. LCH is classified as single or multisystem organ disease. Two-thirds of the cases present with single system involvement. Organs most commonly affected include the bone (the skull being the most commonly affected), skin, and high-risk organs like the liver, spleen, and bone marrow, and less commonly the lungs, lymph nodes, and central nervous system. Some patients can present with fever, lethargy, and weight loss. None were noted in our patient.

Skin findings of LCH can have multiple morphologies and presentations and often described as a big mimicker. In young infants like our patient, the seborrheic dermatitis–mimicking type is often seen. In other cases, the skin lesions can appear eczematous, petechial, with scabbing, crusting, or purpura. Xanthoma-like lesions, like that one our patient had in the back, have also been described. Resistant diaper dermatitis and cradle cap should prompt the clinician to think about LCH. Lesions can be so varied that can present with hypopigmentation (vitiligo like), hyperpigmentation, varicella-like papulo-pustules, and red blue nodules within others. Oral mucosa and nail involvement can also occur.

Bone involvement can present as soft-tissue mass with swelling and pain as it occur in our patient.

Endocrinopathies have been described in patients with LCH including diabetes insipidus, growth hormone deficiency, and less likely thyroid disease.
 

Multidisciplinary care

The diagnosis of LCH in infants necessitates a combination of clinical, radiological, and histopathologic findings. In infants, cutaneous involvement is a frequent initial presentation, with characteristic lesions that are often misdiagnosed as other dermatologic conditions. Timely recognition of these lesions and appropriate skin biopsies for histological examination are essential steps in achieving an accurate diagnosis.

Radiological imaging, including x-rays, CT, and MRI, plays a crucial role in assessing the extent of involvement.

The management of LCH in infants requires a well-coordinated multidisciplinary approach involving pediatric oncologists, dermatologists, radiologists, orthopedic surgeons, and other relevant specialists. Treatment strategies vary depending on the extent of disease involvement and the presence of risk factors. In localized cases, observation with close monitoring may be considered, as some cases of LCH in infants may undergo spontaneous regression. However, cases with severe symptoms, extensive organ involvement, or high-risk features may require systemic therapies.

Chemotherapy agents, including vinblastine and prednisone have been utilized in the treatment of infantile LCH with varying success. The selection of treatment regimens should be tailored to each individual case, considering disease severity, potential toxicities, and long-term effects. In cases of bone lesions causing significant deformities or functional impairment, surgical intervention may be necessary. Skin only disease can be treated with topical corticosteroids.
 

Prognosis

Survival rates in patients with single-organ involvement without risk-organ involvement is close to 100% and with risk-organ involvement of 98% at 5 years.

Long-term follow-up is essential for infants diagnosed with LCH, as recurrence and late effects can occur even after successful treatment. Continued monitoring allows for the timely detection of relapses or the development of secondary complications.

Infants thought to have common skin conditions like eczema, seborrheic dermatitis, or diaper dermatitis not responding to treatment should be referred to pediatric dermatology for evaluation to rule out the possibility of LCH.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1035-44.

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1047-56.

Leung AKC et al. World J Pediatr. 2019 Dec;15(6):536-45.

At the week follow-up, the lesions were unchanged and the swelling on the left lateral eyebrow was worsening. A biopsy of the yellow lesion on the back and one of the scaly papules on the abdomen was performed. A fungal and bacterial cultures were also ordered.

He was referred to ophthalmology for evaluation of the eyelid swelling and an ultrasound was requested.

The skin biopsy showed a clonal proliferation of reniform histiocytes with eosinophils within the dermis. The cells were positive for S100, CD207 (langerin), and CD1a and negative for pancytokeratin and Melan-A, supportive of the diagnosis of Langerhans cell histiocytosis (LCH).
 

Diagnosis

The patient was admitted to the hospital, where a skeletal survey was performed, which showed an asymmetric lucency involving the left frontal calvarium extending to the superior lateral orbital rim. The brain MRI demonstrated a destructive avidly enhancing soft-tissue process which involved the superior left orbital rim likely with some degree of intracranial extension. This lesion exerts mass effect upon surrounding structures to the left ocular globe. With the skin and skeletal findings, the patient was diagnosed with LCH. His blood count was significant for thrombocytopenia. His liver and kidney function were normal. His electrolytes were also with in normal range. He was started on chemotherapy with vinblastine and systemic corticosteroids with resolution of the rash and decrease on the size of the lesion on the orbit within a few weeks.

Infantile LCH is a rare neoplastic disorder of hematopoietic myeloid precursor cells caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway, particularly BRAF-V600E mutation. White male children are mostly affected, with a peak incidence of 1-3 years of age. Nine out of 10 children with cutaneous involvement also have multisystemic disease, such as the case of our patient. LCH is classified as single or multisystem organ disease. Two-thirds of the cases present with single system involvement. Organs most commonly affected include the bone (the skull being the most commonly affected), skin, and high-risk organs like the liver, spleen, and bone marrow, and less commonly the lungs, lymph nodes, and central nervous system. Some patients can present with fever, lethargy, and weight loss. None were noted in our patient.

Skin findings of LCH can have multiple morphologies and presentations and often described as a big mimicker. In young infants like our patient, the seborrheic dermatitis–mimicking type is often seen. In other cases, the skin lesions can appear eczematous, petechial, with scabbing, crusting, or purpura. Xanthoma-like lesions, like that one our patient had in the back, have also been described. Resistant diaper dermatitis and cradle cap should prompt the clinician to think about LCH. Lesions can be so varied that can present with hypopigmentation (vitiligo like), hyperpigmentation, varicella-like papulo-pustules, and red blue nodules within others. Oral mucosa and nail involvement can also occur.

Bone involvement can present as soft-tissue mass with swelling and pain as it occur in our patient.

Endocrinopathies have been described in patients with LCH including diabetes insipidus, growth hormone deficiency, and less likely thyroid disease.
 

Multidisciplinary care

The diagnosis of LCH in infants necessitates a combination of clinical, radiological, and histopathologic findings. In infants, cutaneous involvement is a frequent initial presentation, with characteristic lesions that are often misdiagnosed as other dermatologic conditions. Timely recognition of these lesions and appropriate skin biopsies for histological examination are essential steps in achieving an accurate diagnosis.

Radiological imaging, including x-rays, CT, and MRI, plays a crucial role in assessing the extent of involvement.

The management of LCH in infants requires a well-coordinated multidisciplinary approach involving pediatric oncologists, dermatologists, radiologists, orthopedic surgeons, and other relevant specialists. Treatment strategies vary depending on the extent of disease involvement and the presence of risk factors. In localized cases, observation with close monitoring may be considered, as some cases of LCH in infants may undergo spontaneous regression. However, cases with severe symptoms, extensive organ involvement, or high-risk features may require systemic therapies.

Chemotherapy agents, including vinblastine and prednisone have been utilized in the treatment of infantile LCH with varying success. The selection of treatment regimens should be tailored to each individual case, considering disease severity, potential toxicities, and long-term effects. In cases of bone lesions causing significant deformities or functional impairment, surgical intervention may be necessary. Skin only disease can be treated with topical corticosteroids.
 

Prognosis

Survival rates in patients with single-organ involvement without risk-organ involvement is close to 100% and with risk-organ involvement of 98% at 5 years.

Long-term follow-up is essential for infants diagnosed with LCH, as recurrence and late effects can occur even after successful treatment. Continued monitoring allows for the timely detection of relapses or the development of secondary complications.

Infants thought to have common skin conditions like eczema, seborrheic dermatitis, or diaper dermatitis not responding to treatment should be referred to pediatric dermatology for evaluation to rule out the possibility of LCH.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1035-44.

Krooks J et al. J Am Acad Dermatol. 2018 Jun;78(6):1047-56.

Leung AKC et al. World J Pediatr. 2019 Dec;15(6):536-45.

Adding oral piroxicam to oral levonorgestrel significantly improved the efficacy of emergency contraception, based on data from 860 women.

Oral hormonal emergency contraception (EC) is the most widely used EC method worldwide, but the two currently available drugs, levonorgestrel and ulipristal acetate (UPA), are not effective when given after ovulation, wrote Raymond Hang Wun Li, MD, of the University of Hong Kong, and colleagues. Previous studies suggest that cyclo-oxygenase (COX) inhibitors may disrupt follicular rupture and prevent ovulation, but data on their use in combination with current oral ECs are lacking, the researchers said.

In a study published in The Lancet, the researchers randomized 430 women to receive a single oral dose of 1.5 mg levonorgestrel plus 40 mg of the COX-2 inhibitor piroxicam or 1.5 mg levonorgestrel plus a placebo. The study participants were women aged 18 years and older who requested EC within 72 hours of unprotected sex and who had regular menstrual cycles between 24 and 42 days long. The median age of the participants was 30 years; 97% were Chinese. The median time from intercourse to treatment was 18 hours for both groups.

The primary outcome was the percentage of pregnancies prevented, based on pregnancy status 1-2 weeks after treatment.

One pregnancy occurred in the piroxicam group, compared with seven pregnancies in the placebo group, which translated to a significant difference in the percentage of pregnancies prevented (94.7% vs. 63.4%, P < .0001).

No trend toward increased failure rates appeared based on the time elapsed between intercourse and EC use in either group, and no differences appeared in the return or delay of subsequent menstrual periods between the groups.

The most common adverse events (reported by more than 5% of participants in both groups) included fatigue or weakness, nausea, lower abdominal pain, dizziness, and headache.

The choice of piroxicam as the COX inhibitor in conjunction with levonorgestrel for the current study had several potential advantages, the researchers wrote in their discussion. These advantages include the widespread availability and long-acting characteristics of piroxicam, which is also true of levonorgestrel, they said.

The findings were limited by several factors including the generalizability to other settings and populations, the researchers noted. The efficacy of the levonorgestrel/piroxicam combination in women with a body mass index greater than 26 kg/m² may be lower, but the current study population did not have enough women in this category to measure the potential effect, they said. The study also did not examine the effect of piroxicam in combination with ulipristal acetate.

However, the results are the first known to demonstrate the improved effectiveness of oral piroxicam coadministered with oral levonorgestrel for EC, they said.

“The strength of this recommendation and changes in clinical guidelines may be determined upon demonstration of reproducible results in further studies,” they added.
 

Pill combination shows potential and practicality

Oral emergency contraception on demand is an unmet need on a global level, Erica P. Cahill, MD, of the department of obstetrics and gynecology and division of family planning services at Stanford (Calif.) University, wrote in an accompanying editorial.

Dr. Cahill noted the longer half-life of piroxicam compared with other COX-2 inhibitors, which made it a practical choice. Although the study was not powered to evaluate secondary outcomes, bleeding patterns consistent with use of EC pills were observed. Documentation of these patterns is worthwhile, Dr. Cahill said, “because people using emergency contraceptive pills might also be using fertility awareness methods and need to know when they can be certain they are not pregnant.”

Overall, the study supports the addition of 40 mg piroxicam to 1.5 mg levonorgestrel as emergency contraception, said Dr. Cahill. Future studies can build on the current findings by evaluating repeat dosing of the piroxicam/levonorgestrel combination and by evaluating the combination of COX-2 inhibitors and ulipristal acetate to prevent pregnancy, she said.

The study received no outside funding. The researchers and Dr. Cahill had no financial conflicts to disclose.

Adding oral piroxicam to oral levonorgestrel significantly improved the efficacy of emergency contraception, based on data from 860 women.

Oral hormonal emergency contraception (EC) is the most widely used EC method worldwide, but the two currently available drugs, levonorgestrel and ulipristal acetate (UPA), are not effective when given after ovulation, wrote Raymond Hang Wun Li, MD, of the University of Hong Kong, and colleagues. Previous studies suggest that cyclo-oxygenase (COX) inhibitors may disrupt follicular rupture and prevent ovulation, but data on their use in combination with current oral ECs are lacking, the researchers said.

In a study published in The Lancet, the researchers randomized 430 women to receive a single oral dose of 1.5 mg levonorgestrel plus 40 mg of the COX-2 inhibitor piroxicam or 1.5 mg levonorgestrel plus a placebo. The study participants were women aged 18 years and older who requested EC within 72 hours of unprotected sex and who had regular menstrual cycles between 24 and 42 days long. The median age of the participants was 30 years; 97% were Chinese. The median time from intercourse to treatment was 18 hours for both groups.

The primary outcome was the percentage of pregnancies prevented, based on pregnancy status 1-2 weeks after treatment.

One pregnancy occurred in the piroxicam group, compared with seven pregnancies in the placebo group, which translated to a significant difference in the percentage of pregnancies prevented (94.7% vs. 63.4%, P < .0001).

No trend toward increased failure rates appeared based on the time elapsed between intercourse and EC use in either group, and no differences appeared in the return or delay of subsequent menstrual periods between the groups.

The most common adverse events (reported by more than 5% of participants in both groups) included fatigue or weakness, nausea, lower abdominal pain, dizziness, and headache.

The choice of piroxicam as the COX inhibitor in conjunction with levonorgestrel for the current study had several potential advantages, the researchers wrote in their discussion. These advantages include the widespread availability and long-acting characteristics of piroxicam, which is also true of levonorgestrel, they said.

The findings were limited by several factors including the generalizability to other settings and populations, the researchers noted. The efficacy of the levonorgestrel/piroxicam combination in women with a body mass index greater than 26 kg/m² may be lower, but the current study population did not have enough women in this category to measure the potential effect, they said. The study also did not examine the effect of piroxicam in combination with ulipristal acetate.

However, the results are the first known to demonstrate the improved effectiveness of oral piroxicam coadministered with oral levonorgestrel for EC, they said.

“The strength of this recommendation and changes in clinical guidelines may be determined upon demonstration of reproducible results in further studies,” they added.
 

Pill combination shows potential and practicality

Oral emergency contraception on demand is an unmet need on a global level, Erica P. Cahill, MD, of the department of obstetrics and gynecology and division of family planning services at Stanford (Calif.) University, wrote in an accompanying editorial.

Dr. Cahill noted the longer half-life of piroxicam compared with other COX-2 inhibitors, which made it a practical choice. Although the study was not powered to evaluate secondary outcomes, bleeding patterns consistent with use of EC pills were observed. Documentation of these patterns is worthwhile, Dr. Cahill said, “because people using emergency contraceptive pills might also be using fertility awareness methods and need to know when they can be certain they are not pregnant.”

Overall, the study supports the addition of 40 mg piroxicam to 1.5 mg levonorgestrel as emergency contraception, said Dr. Cahill. Future studies can build on the current findings by evaluating repeat dosing of the piroxicam/levonorgestrel combination and by evaluating the combination of COX-2 inhibitors and ulipristal acetate to prevent pregnancy, she said.

The study received no outside funding. The researchers and Dr. Cahill had no financial conflicts to disclose.

Adding oral piroxicam to oral levonorgestrel significantly improved the efficacy of emergency contraception, based on data from 860 women.

Oral hormonal emergency contraception (EC) is the most widely used EC method worldwide, but the two currently available drugs, levonorgestrel and ulipristal acetate (UPA), are not effective when given after ovulation, wrote Raymond Hang Wun Li, MD, of the University of Hong Kong, and colleagues. Previous studies suggest that cyclo-oxygenase (COX) inhibitors may disrupt follicular rupture and prevent ovulation, but data on their use in combination with current oral ECs are lacking, the researchers said.

In a study published in The Lancet, the researchers randomized 430 women to receive a single oral dose of 1.5 mg levonorgestrel plus 40 mg of the COX-2 inhibitor piroxicam or 1.5 mg levonorgestrel plus a placebo. The study participants were women aged 18 years and older who requested EC within 72 hours of unprotected sex and who had regular menstrual cycles between 24 and 42 days long. The median age of the participants was 30 years; 97% were Chinese. The median time from intercourse to treatment was 18 hours for both groups.

The primary outcome was the percentage of pregnancies prevented, based on pregnancy status 1-2 weeks after treatment.

One pregnancy occurred in the piroxicam group, compared with seven pregnancies in the placebo group, which translated to a significant difference in the percentage of pregnancies prevented (94.7% vs. 63.4%, P < .0001).

No trend toward increased failure rates appeared based on the time elapsed between intercourse and EC use in either group, and no differences appeared in the return or delay of subsequent menstrual periods between the groups.

The most common adverse events (reported by more than 5% of participants in both groups) included fatigue or weakness, nausea, lower abdominal pain, dizziness, and headache.

The choice of piroxicam as the COX inhibitor in conjunction with levonorgestrel for the current study had several potential advantages, the researchers wrote in their discussion. These advantages include the widespread availability and long-acting characteristics of piroxicam, which is also true of levonorgestrel, they said.

The findings were limited by several factors including the generalizability to other settings and populations, the researchers noted. The efficacy of the levonorgestrel/piroxicam combination in women with a body mass index greater than 26 kg/m² may be lower, but the current study population did not have enough women in this category to measure the potential effect, they said. The study also did not examine the effect of piroxicam in combination with ulipristal acetate.

However, the results are the first known to demonstrate the improved effectiveness of oral piroxicam coadministered with oral levonorgestrel for EC, they said.

“The strength of this recommendation and changes in clinical guidelines may be determined upon demonstration of reproducible results in further studies,” they added.
 

Pill combination shows potential and practicality

Oral emergency contraception on demand is an unmet need on a global level, Erica P. Cahill, MD, of the department of obstetrics and gynecology and division of family planning services at Stanford (Calif.) University, wrote in an accompanying editorial.

Dr. Cahill noted the longer half-life of piroxicam compared with other COX-2 inhibitors, which made it a practical choice. Although the study was not powered to evaluate secondary outcomes, bleeding patterns consistent with use of EC pills were observed. Documentation of these patterns is worthwhile, Dr. Cahill said, “because people using emergency contraceptive pills might also be using fertility awareness methods and need to know when they can be certain they are not pregnant.”

Overall, the study supports the addition of 40 mg piroxicam to 1.5 mg levonorgestrel as emergency contraception, said Dr. Cahill. Future studies can build on the current findings by evaluating repeat dosing of the piroxicam/levonorgestrel combination and by evaluating the combination of COX-2 inhibitors and ulipristal acetate to prevent pregnancy, she said.

The study received no outside funding. The researchers and Dr. Cahill had no financial conflicts to disclose.

Every 4 years, an interprofessional panel of experts from the American Geriatrics Society provides updated guidelines on safe prescribing of medications in older adults, known as the Beers Criteria. A 2023 update was released in May 2023 after panel review of more 1,500 clinical trials and research studies published since the last update.

Anticoagulants

Notable changes to the 2023 guidelines include updated recommendations for anticoagulation. Warfarin should be avoided as initial therapy for venous thromboembolism or nonvalvular atrial fibrillation unless there are contraindications to direct oral anticoagulants (DOACs) or other substantial barriers to use.

Rivaroxaban should also be avoided, and dabigatran used with caution in favor of apixaban, which is felt to have a better safety profile in older adults. Rivaroxaban may be considered if once daily dosing is deemed to be more clinically appropriate. Financial barriers regarding drug coverage and formulary options were acknowledged as a significant barrier to equitable access to preferred direct oral anticoagulants in older adults.
 

Diabetes medication

Regarding diabetes management, short-acting sulfonylureas should be avoided in addition to long-acting sulfonylureas, because of the increased risk of hypoglycemia, and cardiovascular and all-cause mortality in older adults. Sodium-glucose cotransporter 2 inhibitors as an entire class are recommended to be used with caution, as older adults are at higher risk of euglycemic ketoacidosis and urogenital infections, particularly in women in the first month of initiating treatment.

Like DOACs, the panel acknowledged that financial considerations may lead to limited options for oral diabetic treatment. In circumstances where a sulfonylurea is used, short-acting forms are preferred over long acting to reduce the risk of prolonged hypoglycemia.
 

Aspirin for primary prevention

Alongside the U.S. Preventive Services Task Force guideline update in 2022 regarding aspirin for primary prevention of cardiovascular disease and stroke, the Beer’s Criteria recommend against initiation of aspirin for primary prevention in older adults. Ticagrelor and prasugrel should be used with caution because of the increased risk of major bleeding in older adults over the age of 75, compared with clopidogrel. If prasugrel is used, a lower dose of 5 mg is recommended, in line with guidelines by the American College of Cardiology and American Heart Association.

Pain medication

For pain management, the Beer’s Criteria updated recommendations to avoid NSAIDs, particularly when used in combination with steroids or anticoagulants. The panel highlights that even short-term use of NSAIDs is high risk when used in combination with steroids or anticoagulants. If no other alternatives are possible, patients should be placed on a proton pump inhibitor or misoprostol while taking NSAIDs.

Baclofen should be avoided in older adults with renal insufficiency (estimated glomerular filtration rate < 60 mL/min per 1.73 m²) because of the increased risk of encephalopathy, and when used, should be given at the lowest effective dose with close monitoring for mental status changes.
 

Androgen and estrogen replacement therapy

For androgen replacement therapy, the panel notes that testosterone supplementation should be avoided because of cardiovascular risks unless there is confirmed hypogonadism. The panel revised their recommendation on the basis of emerging data that a history of prostate cancer is not an absolute contraindication for exogenous testosterone. A risk versus benefit discussion about exogenous testosterone should be had with a medical oncologist or urologist in those with a history of prostate cancer.

Regarding estrogen, systemic formulations should not be initiated in women over the age of 60 because of increased risk of cardiovascular events, venous thromboembolism, and dementia. In women with a history of breast cancer, vaginal estrogens are generally felt to be safe to use at low doses, such as less than 25 mcg twice weekly.

Dr. Wang is a geriatrician and general internist at Harborview Medical Center, Seattle.

Every 4 years, an interprofessional panel of experts from the American Geriatrics Society provides updated guidelines on safe prescribing of medications in older adults, known as the Beers Criteria. A 2023 update was released in May 2023 after panel review of more 1,500 clinical trials and research studies published since the last update.

Anticoagulants

Notable changes to the 2023 guidelines include updated recommendations for anticoagulation. Warfarin should be avoided as initial therapy for venous thromboembolism or nonvalvular atrial fibrillation unless there are contraindications to direct oral anticoagulants (DOACs) or other substantial barriers to use.

Rivaroxaban should also be avoided, and dabigatran used with caution in favor of apixaban, which is felt to have a better safety profile in older adults. Rivaroxaban may be considered if once daily dosing is deemed to be more clinically appropriate. Financial barriers regarding drug coverage and formulary options were acknowledged as a significant barrier to equitable access to preferred direct oral anticoagulants in older adults.
 

Diabetes medication

Regarding diabetes management, short-acting sulfonylureas should be avoided in addition to long-acting sulfonylureas, because of the increased risk of hypoglycemia, and cardiovascular and all-cause mortality in older adults. Sodium-glucose cotransporter 2 inhibitors as an entire class are recommended to be used with caution, as older adults are at higher risk of euglycemic ketoacidosis and urogenital infections, particularly in women in the first month of initiating treatment.

Like DOACs, the panel acknowledged that financial considerations may lead to limited options for oral diabetic treatment. In circumstances where a sulfonylurea is used, short-acting forms are preferred over long acting to reduce the risk of prolonged hypoglycemia.
 

Aspirin for primary prevention

Alongside the U.S. Preventive Services Task Force guideline update in 2022 regarding aspirin for primary prevention of cardiovascular disease and stroke, the Beer’s Criteria recommend against initiation of aspirin for primary prevention in older adults. Ticagrelor and prasugrel should be used with caution because of the increased risk of major bleeding in older adults over the age of 75, compared with clopidogrel. If prasugrel is used, a lower dose of 5 mg is recommended, in line with guidelines by the American College of Cardiology and American Heart Association.

Pain medication

For pain management, the Beer’s Criteria updated recommendations to avoid NSAIDs, particularly when used in combination with steroids or anticoagulants. The panel highlights that even short-term use of NSAIDs is high risk when used in combination with steroids or anticoagulants. If no other alternatives are possible, patients should be placed on a proton pump inhibitor or misoprostol while taking NSAIDs.

Baclofen should be avoided in older adults with renal insufficiency (estimated glomerular filtration rate < 60 mL/min per 1.73 m²) because of the increased risk of encephalopathy, and when used, should be given at the lowest effective dose with close monitoring for mental status changes.
 

Androgen and estrogen replacement therapy

For androgen replacement therapy, the panel notes that testosterone supplementation should be avoided because of cardiovascular risks unless there is confirmed hypogonadism. The panel revised their recommendation on the basis of emerging data that a history of prostate cancer is not an absolute contraindication for exogenous testosterone. A risk versus benefit discussion about exogenous testosterone should be had with a medical oncologist or urologist in those with a history of prostate cancer.

Regarding estrogen, systemic formulations should not be initiated in women over the age of 60 because of increased risk of cardiovascular events, venous thromboembolism, and dementia. In women with a history of breast cancer, vaginal estrogens are generally felt to be safe to use at low doses, such as less than 25 mcg twice weekly.

Dr. Wang is a geriatrician and general internist at Harborview Medical Center, Seattle.

Every 4 years, an interprofessional panel of experts from the American Geriatrics Society provides updated guidelines on safe prescribing of medications in older adults, known as the Beers Criteria. A 2023 update was released in May 2023 after panel review of more 1,500 clinical trials and research studies published since the last update.

Anticoagulants

Notable changes to the 2023 guidelines include updated recommendations for anticoagulation. Warfarin should be avoided as initial therapy for venous thromboembolism or nonvalvular atrial fibrillation unless there are contraindications to direct oral anticoagulants (DOACs) or other substantial barriers to use.

Rivaroxaban should also be avoided, and dabigatran used with caution in favor of apixaban, which is felt to have a better safety profile in older adults. Rivaroxaban may be considered if once daily dosing is deemed to be more clinically appropriate. Financial barriers regarding drug coverage and formulary options were acknowledged as a significant barrier to equitable access to preferred direct oral anticoagulants in older adults.
 

Diabetes medication

Regarding diabetes management, short-acting sulfonylureas should be avoided in addition to long-acting sulfonylureas, because of the increased risk of hypoglycemia, and cardiovascular and all-cause mortality in older adults. Sodium-glucose cotransporter 2 inhibitors as an entire class are recommended to be used with caution, as older adults are at higher risk of euglycemic ketoacidosis and urogenital infections, particularly in women in the first month of initiating treatment.

Like DOACs, the panel acknowledged that financial considerations may lead to limited options for oral diabetic treatment. In circumstances where a sulfonylurea is used, short-acting forms are preferred over long acting to reduce the risk of prolonged hypoglycemia.
 

Aspirin for primary prevention

Alongside the U.S. Preventive Services Task Force guideline update in 2022 regarding aspirin for primary prevention of cardiovascular disease and stroke, the Beer’s Criteria recommend against initiation of aspirin for primary prevention in older adults. Ticagrelor and prasugrel should be used with caution because of the increased risk of major bleeding in older adults over the age of 75, compared with clopidogrel. If prasugrel is used, a lower dose of 5 mg is recommended, in line with guidelines by the American College of Cardiology and American Heart Association.

Pain medication

For pain management, the Beer’s Criteria updated recommendations to avoid NSAIDs, particularly when used in combination with steroids or anticoagulants. The panel highlights that even short-term use of NSAIDs is high risk when used in combination with steroids or anticoagulants. If no other alternatives are possible, patients should be placed on a proton pump inhibitor or misoprostol while taking NSAIDs.

Baclofen should be avoided in older adults with renal insufficiency (estimated glomerular filtration rate < 60 mL/min per 1.73 m²) because of the increased risk of encephalopathy, and when used, should be given at the lowest effective dose with close monitoring for mental status changes.
 

Androgen and estrogen replacement therapy

For androgen replacement therapy, the panel notes that testosterone supplementation should be avoided because of cardiovascular risks unless there is confirmed hypogonadism. The panel revised their recommendation on the basis of emerging data that a history of prostate cancer is not an absolute contraindication for exogenous testosterone. A risk versus benefit discussion about exogenous testosterone should be had with a medical oncologist or urologist in those with a history of prostate cancer.

Regarding estrogen, systemic formulations should not be initiated in women over the age of 60 because of increased risk of cardiovascular events, venous thromboembolism, and dementia. In women with a history of breast cancer, vaginal estrogens are generally felt to be safe to use at low doses, such as less than 25 mcg twice weekly.

Dr. Wang is a geriatrician and general internist at Harborview Medical Center, Seattle.

The anti–amyloid-beta monoclonal antibodies lecanemab and aducanumab have introduced a new class of drugs for targeting early stage Alzheimer’s disease, but fewer than 10% of older adults with early signs of the disease would meet eligibility requirements to receive either treatment, a cross sectional study has found.

Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.

Mayo Clinic

“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
 

Applying clinical trial exclusion criteria to a broader population

The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).

The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.

For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m² was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.

When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.

Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.

“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”

Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”

One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.
 

Estimating the number of patients who would qualify for treatment

In an accompanying commentary, Matthew Howes, MD, of Butler Hospital and Brown University in Providence, R.I., and colleagues wrote that the study findings provide health systems planning to offer amyloid-lowering antibodies for Alzheimer’s disease an estimate of how many patients would be eligible for the treatments. “Providers must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” the commentators wrote.

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation, and the Schuler Foundation. Dr. Vassilaki disclosed relationships with F. Hoffmann-La Roche, Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no relevant disclosures.
 

The anti–amyloid-beta monoclonal antibodies lecanemab and aducanumab have introduced a new class of drugs for targeting early stage Alzheimer’s disease, but fewer than 10% of older adults with early signs of the disease would meet eligibility requirements to receive either treatment, a cross sectional study has found.

Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.

Mayo Clinic

“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
 

Applying clinical trial exclusion criteria to a broader population

The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).

The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.

For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m² was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.

When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.

Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.

“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”

Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”

One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.
 

Estimating the number of patients who would qualify for treatment

In an accompanying commentary, Matthew Howes, MD, of Butler Hospital and Brown University in Providence, R.I., and colleagues wrote that the study findings provide health systems planning to offer amyloid-lowering antibodies for Alzheimer’s disease an estimate of how many patients would be eligible for the treatments. “Providers must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” the commentators wrote.

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation, and the Schuler Foundation. Dr. Vassilaki disclosed relationships with F. Hoffmann-La Roche, Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no relevant disclosures.
 

The anti–amyloid-beta monoclonal antibodies lecanemab and aducanumab have introduced a new class of drugs for targeting early stage Alzheimer’s disease, but fewer than 10% of older adults with early signs of the disease would meet eligibility requirements to receive either treatment, a cross sectional study has found.

Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.

Mayo Clinic

“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
 

Applying clinical trial exclusion criteria to a broader population

The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).

The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.

For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m² was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.

When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.

Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.

“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”

Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”

One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.
 

Estimating the number of patients who would qualify for treatment

In an accompanying commentary, Matthew Howes, MD, of Butler Hospital and Brown University in Providence, R.I., and colleagues wrote that the study findings provide health systems planning to offer amyloid-lowering antibodies for Alzheimer’s disease an estimate of how many patients would be eligible for the treatments. “Providers must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” the commentators wrote.

The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation, and the Schuler Foundation. Dr. Vassilaki disclosed relationships with F. Hoffmann-La Roche, Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no relevant disclosures.