User login
Resmetirom Reduces Liver Stiffness in MASH Cirrhosis
PHOENIX — according to the results of a new study.
As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.
Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.
According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.
In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.
Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.
At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.
After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.
Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.
Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.
Changing the Treatment Landscape for MASH-Related Cirrhosis
When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”
Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.
A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.
“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.
“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.
Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.
A version of this article appeared on Medscape.com.
PHOENIX — according to the results of a new study.
As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.
Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.
According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.
In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.
Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.
At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.
After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.
Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.
Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.
Changing the Treatment Landscape for MASH-Related Cirrhosis
When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”
Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.
A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.
“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.
“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.
Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.
A version of this article appeared on Medscape.com.
PHOENIX — according to the results of a new study.
As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.
Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.
According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.
In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.
Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.
At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.
After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.
Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.
Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.
Changing the Treatment Landscape for MASH-Related Cirrhosis
When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”
Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.
A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.
“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.
“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.
Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.
A version of this article appeared on Medscape.com.
FROM ACG 2025
Vaping Increases Peptic Ulcer Disease Risk
PHOENIX — , a cross-sectional study found.
The study also found increased risk of PUD among former users of e-cigarettes, reported Albert E. Ohrin, MBChB, MHS, of Ascension Saint Agnes Hospital, Baltimore, Maryland, who presented the study here at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
While cigarette smoking is a known risk factor for PUD, there was little in the literature investigating whether vaping has a similar risk profile, said Ohrin, a first-year internal medicine resident. He told GI & Hepatology News he found e-cigarette users on Reddit discussing worsening PUD and decided to investigate further, especially since vaping is so popular among young people.
E-cigarettes are the most-used tobacco product among middle and high school students. The National Youth Tobacco Survey in the US reported that 1.6 million students (5.9%) vaped in 2024, a decline from 7.7% in 2023. And the number of adults using e-cigarettes is increasing, according to the US CDC. In 2023, 6.5% of adults over age 18 used e-cigarettes, up from 3.7% in 2020.
Ohrin and colleagues conducted a cross-sectional analysis of adults enrolled in the National Institutes of Health All of Us Research Program. Participants self-reported e-cigarette use. PUD was defined using validated electronic health record diagnosis codes.
Among the 371,398 participants, 29,373 (8%) reported using e-cigarettes, including 21,277 current users and 8096 former users. E-cigarette users were significantly younger (mean age 45.3 vs 59.3 years; P < .001), more likely to be female, and more likely to report lower education and income (P < .001).
Current e-cigarette users had 27% higher odds of PUD (adjusted odds ratio [aOR], 1.27; 95% CI, 1.12-1.45), compared to never-users. This was greater than the risk with traditional combustible cigarettes (aOR, 1.19) that was seen in the study.
Former e-cig users had 13% higher odds (aOR, 1.13; 95% CI, 1.04-1.24) compared to never-users, and any e-cigarette use was associated with higher odds of PUD (aOR, 1.17; 95% CI, 1.09-1.26) compared to never-use.
Use of non-steroidal anti-inflammatories (aOR, 2.15) and having gastroesophageal reflux disease (aOR, 4.45) presented the most significant PUD risk.
Ohrin said he and his colleagues were surprised to see that people who had stopped using e-cigarettes still had higher odds of PUD, although he pointed out that the researchers did not know the frequency of use or how long users had stopped.
“Now that we know there’s an association, we are going to do more studies on e-cigarettes” to see what the potential harms are, especially on the gastrointestinal system, he told GI & Hepatology News.
“One of the things we are looking to elicit is — is there a dose response?” he said, noting it would take a prospective trial to determine that effect.
‘Opens a Door’ to Looking at the GI System
Laura Crotty Alexander, MD, a professor of medicine and associate division chief of pulmonary, critical care, sleep medicine, and physiology at the University of California, San Diego, said she found the study novel and interesting.
“It’s the first I’ve heard of an association between e-cigarette vaping and peptic ulcer disease,” said Crotty Alexander, who has studied the health effects of e-cigarettes for a decade.
Previous studies have shown that nicotine itself can drive an increase in gastric acid production and decrease healing, which can contribute to PUD, Crotty Alexander told GI & Hepatology News. With combustible cigarettes, it is thought that “the larger drivers of that association are the other things in tobacco smoke, such as tar and carbon monoxide and a million other horrible chemicals,” she said.
Crotty Alexander and her colleagues have conducted studies in vitro and in mice that show that e-cigarette aerosols are irritants and cause oxidative stress, which can drive PUD.
While many studies have shown vaping impacts various organs, Ohrin’s study “opens a door” to start looking at the gastrointestinal system, she said.
The study is also a signal to clinicians to “take an accurate inhalant history,” which means asking about vaping, she added.
Ohrin and Crotty Alexander reported no conflicts.
A version of this article first appeared on Medscape.com.
PHOENIX — , a cross-sectional study found.
The study also found increased risk of PUD among former users of e-cigarettes, reported Albert E. Ohrin, MBChB, MHS, of Ascension Saint Agnes Hospital, Baltimore, Maryland, who presented the study here at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
While cigarette smoking is a known risk factor for PUD, there was little in the literature investigating whether vaping has a similar risk profile, said Ohrin, a first-year internal medicine resident. He told GI & Hepatology News he found e-cigarette users on Reddit discussing worsening PUD and decided to investigate further, especially since vaping is so popular among young people.
E-cigarettes are the most-used tobacco product among middle and high school students. The National Youth Tobacco Survey in the US reported that 1.6 million students (5.9%) vaped in 2024, a decline from 7.7% in 2023. And the number of adults using e-cigarettes is increasing, according to the US CDC. In 2023, 6.5% of adults over age 18 used e-cigarettes, up from 3.7% in 2020.
Ohrin and colleagues conducted a cross-sectional analysis of adults enrolled in the National Institutes of Health All of Us Research Program. Participants self-reported e-cigarette use. PUD was defined using validated electronic health record diagnosis codes.
Among the 371,398 participants, 29,373 (8%) reported using e-cigarettes, including 21,277 current users and 8096 former users. E-cigarette users were significantly younger (mean age 45.3 vs 59.3 years; P < .001), more likely to be female, and more likely to report lower education and income (P < .001).
Current e-cigarette users had 27% higher odds of PUD (adjusted odds ratio [aOR], 1.27; 95% CI, 1.12-1.45), compared to never-users. This was greater than the risk with traditional combustible cigarettes (aOR, 1.19) that was seen in the study.
Former e-cig users had 13% higher odds (aOR, 1.13; 95% CI, 1.04-1.24) compared to never-users, and any e-cigarette use was associated with higher odds of PUD (aOR, 1.17; 95% CI, 1.09-1.26) compared to never-use.
Use of non-steroidal anti-inflammatories (aOR, 2.15) and having gastroesophageal reflux disease (aOR, 4.45) presented the most significant PUD risk.
Ohrin said he and his colleagues were surprised to see that people who had stopped using e-cigarettes still had higher odds of PUD, although he pointed out that the researchers did not know the frequency of use or how long users had stopped.
“Now that we know there’s an association, we are going to do more studies on e-cigarettes” to see what the potential harms are, especially on the gastrointestinal system, he told GI & Hepatology News.
“One of the things we are looking to elicit is — is there a dose response?” he said, noting it would take a prospective trial to determine that effect.
‘Opens a Door’ to Looking at the GI System
Laura Crotty Alexander, MD, a professor of medicine and associate division chief of pulmonary, critical care, sleep medicine, and physiology at the University of California, San Diego, said she found the study novel and interesting.
“It’s the first I’ve heard of an association between e-cigarette vaping and peptic ulcer disease,” said Crotty Alexander, who has studied the health effects of e-cigarettes for a decade.
Previous studies have shown that nicotine itself can drive an increase in gastric acid production and decrease healing, which can contribute to PUD, Crotty Alexander told GI & Hepatology News. With combustible cigarettes, it is thought that “the larger drivers of that association are the other things in tobacco smoke, such as tar and carbon monoxide and a million other horrible chemicals,” she said.
Crotty Alexander and her colleagues have conducted studies in vitro and in mice that show that e-cigarette aerosols are irritants and cause oxidative stress, which can drive PUD.
While many studies have shown vaping impacts various organs, Ohrin’s study “opens a door” to start looking at the gastrointestinal system, she said.
The study is also a signal to clinicians to “take an accurate inhalant history,” which means asking about vaping, she added.
Ohrin and Crotty Alexander reported no conflicts.
A version of this article first appeared on Medscape.com.
PHOENIX — , a cross-sectional study found.
The study also found increased risk of PUD among former users of e-cigarettes, reported Albert E. Ohrin, MBChB, MHS, of Ascension Saint Agnes Hospital, Baltimore, Maryland, who presented the study here at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
While cigarette smoking is a known risk factor for PUD, there was little in the literature investigating whether vaping has a similar risk profile, said Ohrin, a first-year internal medicine resident. He told GI & Hepatology News he found e-cigarette users on Reddit discussing worsening PUD and decided to investigate further, especially since vaping is so popular among young people.
E-cigarettes are the most-used tobacco product among middle and high school students. The National Youth Tobacco Survey in the US reported that 1.6 million students (5.9%) vaped in 2024, a decline from 7.7% in 2023. And the number of adults using e-cigarettes is increasing, according to the US CDC. In 2023, 6.5% of adults over age 18 used e-cigarettes, up from 3.7% in 2020.
Ohrin and colleagues conducted a cross-sectional analysis of adults enrolled in the National Institutes of Health All of Us Research Program. Participants self-reported e-cigarette use. PUD was defined using validated electronic health record diagnosis codes.
Among the 371,398 participants, 29,373 (8%) reported using e-cigarettes, including 21,277 current users and 8096 former users. E-cigarette users were significantly younger (mean age 45.3 vs 59.3 years; P < .001), more likely to be female, and more likely to report lower education and income (P < .001).
Current e-cigarette users had 27% higher odds of PUD (adjusted odds ratio [aOR], 1.27; 95% CI, 1.12-1.45), compared to never-users. This was greater than the risk with traditional combustible cigarettes (aOR, 1.19) that was seen in the study.
Former e-cig users had 13% higher odds (aOR, 1.13; 95% CI, 1.04-1.24) compared to never-users, and any e-cigarette use was associated with higher odds of PUD (aOR, 1.17; 95% CI, 1.09-1.26) compared to never-use.
Use of non-steroidal anti-inflammatories (aOR, 2.15) and having gastroesophageal reflux disease (aOR, 4.45) presented the most significant PUD risk.
Ohrin said he and his colleagues were surprised to see that people who had stopped using e-cigarettes still had higher odds of PUD, although he pointed out that the researchers did not know the frequency of use or how long users had stopped.
“Now that we know there’s an association, we are going to do more studies on e-cigarettes” to see what the potential harms are, especially on the gastrointestinal system, he told GI & Hepatology News.
“One of the things we are looking to elicit is — is there a dose response?” he said, noting it would take a prospective trial to determine that effect.
‘Opens a Door’ to Looking at the GI System
Laura Crotty Alexander, MD, a professor of medicine and associate division chief of pulmonary, critical care, sleep medicine, and physiology at the University of California, San Diego, said she found the study novel and interesting.
“It’s the first I’ve heard of an association between e-cigarette vaping and peptic ulcer disease,” said Crotty Alexander, who has studied the health effects of e-cigarettes for a decade.
Previous studies have shown that nicotine itself can drive an increase in gastric acid production and decrease healing, which can contribute to PUD, Crotty Alexander told GI & Hepatology News. With combustible cigarettes, it is thought that “the larger drivers of that association are the other things in tobacco smoke, such as tar and carbon monoxide and a million other horrible chemicals,” she said.
Crotty Alexander and her colleagues have conducted studies in vitro and in mice that show that e-cigarette aerosols are irritants and cause oxidative stress, which can drive PUD.
While many studies have shown vaping impacts various organs, Ohrin’s study “opens a door” to start looking at the gastrointestinal system, she said.
The study is also a signal to clinicians to “take an accurate inhalant history,” which means asking about vaping, she added.
Ohrin and Crotty Alexander reported no conflicts.
A version of this article first appeared on Medscape.com.
FROM ACG 2025
At-Home Alzheimer’s Testing Is Here: Are Physicians Ready?
Given the opportunity, 90% of Americans say they would take a blood biomarker test for Alzheimer’s disease (AD) — even in the absence of symptoms. Notably, 80% say they wouldn’t wait for a physician to order a test, they’d request one themselves.
The findings, from a recent nationwide survey by the Alzheimer’s Association, suggest a growing desire to predict the risk for or show evidence of AD and related dementias with a simple blood test. For consumers with the inclination and the money, that desire can now become reality.
Once limited to research settings or only available via a physician’s order, blood-based diagnostics for specific biomarkers — primarily pTau-217 and beta-amyloid 42/20 — are now offered by at least four companies in the US. Several others sell blood-based “dementia” panels without those biomarkers and screens for apolipoprotein (APOE) genes, including APOE4, a variant that confers a higher risk for AD.
The companies promote testing to all comers, not just those with a family history or concerns about cognitive symptoms. Test prices range from hundreds to thousands of dollars, depending on whether they are included in a company membership, often designed to encourage repeat testing. Blood draws are conducted at home or at certified labs. Buyers don’t need a prescription or to consult with a physician after receiving results.
Knowing results of such tests could be empowering and may encourage people to prepare for their illness, Jessica Mozersky, PhD, assistant professor of medicine at the Bioethics Research Center at Washington University in St. Louis, told this news organization. A direct-to-consumer (DTC) test also eliminates potential physician-created barriers to testing, she added.
But there are also potential harms.
Based on results, individuals may interpret everyday forgetfulness — like misplacing keys — as a sign that dementia is inevitable. This can lead them to change life plans, rethink the way they spend their time, or begin viewing their future negatively. “It creates unnecessary worry and anxiety,” Mozersky said.
The growing availability of DTC tests — heralded by some experts and discouraged by others — comes as AD and dementia specialists continue to debate whether AD diagnostic and staging criteria should be based only on biomarkers or on criteria that includes both pathology and symptomology.
For many, it raises a fundamental concern: If experts haven’t reached a consensus on blood-based AD biomarker testing, how can consumers be expected to interpret at-home test results?
Growing Demand
In 2024, the number of people living with AD passed 7 million. A recent report from the Alzheimer’s Association estimates that number will nearly double by 2060.
The demand for testing also appears to be rising. Similar to the findings in the Alzheimer’s Association’s survey, a small observational study published last year showed that 90% of patients who received a cerebrospinal fluid AD biomarker test ordered by a physician said the decision to get the test was “easy.” For 82%, getting results was positive because it allowed them to plan ahead and to adopt or continue healthy behaviors such as exercise and cognitive activities.
Until now, blood biomarker tests for AD have primarily been available only through a doctor. The tests measure beta-amyloid 42/20 and pTau-217, both of which are strong biomarkers of AD. Some other blood-based biomarkers under investigation include neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).
As reported by Medscape Medical News, the FDA approved the first blood-based AD diagnostic test in May. The Lumipulse G pTau 217/Beta-Amyloid 1-42 is for the early detection of amyloid plaques associated with AD in adults aged 55 years or older who show signs and symptoms of the disease. But it is only available by prescription.
Quest Diagnostics tested the DTC market in 2023, promoting a consumer-initiated test for beta-amyloid 42/40 that had previously been available only through physicians. It was not well-received by clinicians and ethicists. The company withdrew it later that year but continues to sell beta-amyloid 42/20 and pTau-217 tests through physicians, as does its competitor Labcorp.
Today, at least a handful of companies in the US market AD biomarkers directly to the public: Apollo Health, BetterBrain, Function Health, Neurogen Biomarking, and True Health Labs. None of the companies have disclosed ties to pharmaceutical or device companies or test developers.
What Can Consumers Get?
Some companies direct customers to a lab for blood sample collection, whereas others send a technician to customers’ homes. The extent of biomarker testing and posttest consultation also vary by company.
Apollo Health customers can order a “BrainScan” for $799, which includes screens for pTau-217, GFAP, and NfL. Buyers get a detailed report that explains each test, the result (in nanograms per liter) and optimal range (ng/L) and potential next steps. A pTau-217 result in the normal range, for instance, would come with a recommendation for repeat testing every 2 years. If someone receives an abnormal result, they are contacted by a health coach who can make a physician referral.
At Function Health, members pay $499 a year to have access to hundreds of tests and a written summary of results by a clinician. All of its “Brain Health” tests, including “Beta-Amyloid 42/40 Ratio,” pTau-217, APOE, MTHFR, DNA, and NfL, are available for an additional undisclosed charge.
BetterBrain has a $399 membership that covers an initial 75-minute consultation with cognitive tests, a “personalized brain health plan,” and a blood test that is a basic panel without AD biomarkers. A $499 membership includes all of that plus an APOE test. A pTau-217 test is available for an additional undisclosed fee.
At Neurogen Biomarking, which started in January, a consumer orders an at-home test kit, and a phlebotomist comes to their home for a blood draw. The consumer then fills out an online cognitive assessment. Test results are reviewed by a board-certified neurologist and discussed with the consumer via a virtual visit. If the person is at low-risk, they are given some educational material. Those at higher risk are referred to Neurogen’s “team of specialty-trained neurologists” for continuing care. Testing costs were not provided by the company.
Consumers can order “Beta-Amyloid 42/40” for $749 and pTau-217 for $229 directly through True Health Labs. No consultations or services are offered.
DTC Testing Raises Alarms
It’s unclear where DTC tests fall in terms of regulation. The FDA does not usually review at-home tests for low-risk medical purposes but will generally do so for diagnostics that are for higher-risk conditions “to determine the validity of test claims,” according to the agency’s website.
Consumers, however, don’t usually have easy access to information on biomarker tests’ sensitivity, specificity, or other characteristics that would be used by clinicians or regulatory authorities to assess a test’s validity.
The lack of regulation of consumer-initiated AD testing is one issue cited by critics of at-home tests, including the Alzheimer’s Association.
“None of these tests have been scientifically proven to be accurate,” the association noted in a statement, adding that “the tests can have false positive results, meaning that individuals can have results saying they have dementia when in fact they do not.”
“For these and other reasons, the Alzheimer’s Association believes that home screening tests cannot and should not be used as a substitute for a thorough examination by a skilled physician. The whole process of assessment and diagnosis should be carried out within the context of an ongoing relationship with a responsible and qualified healthcare professional,” the statement said.
The association also said that biomarker tests should not be ordered — even by physicians — for asymptomatic individuals.
The American Academy of Neurology (AAN) does not have a position on DTC tests for AD biomarkers, a spokesperson told this news organization. In a 2021 paper on ethical considerations for diagnosis and care, an AAN committee said that biomarker testing could be clinically useful for some symptomatic patients, but testing asymptomatic individuals is “recommended solely in a research setting” because of potential harms “and the absence of interventions capable of favorably altering the natural history of the disease.”
Eric Topol, MD, chair of the Department of Translational Medicine at Scripps Research in La Jolla, California, is bullish on the potential for blood-based biomarker tests. In a blog post, he called the pTau-217 biomarker “one of the most exciting advances in neurology for decades, giving us a new opportunity to accurately predict and potentially prevent (or at least substantially delay) mild cognitive impairment and Alzheimer’s.”
But, wrote Topol, who is the former editor in chief of MedscapeMedical News, “I don’t think these biomarkers are going to be useful in people at low risk.” He wrote that testing should not be used by people who are “cognitively intact” or to tell someone they have pre-AD. “More work needs to be done to determine whether lowering one’s pTau-217 will alter the brain plaque progression and be seen as a disease-modifier,” wrote Topol.
The Risks of Knowing
Some people don’t want to know their biomarker status. In a study in May in JAMA Network Open, Mozersky and colleagues reported that while 81% of a group of cognitively normal participants in a longitudinal study of dementia said they wanted to see results, only 60% ultimately opted to get results after testing. Participants said they did not want to know because they didn’t want to become a burden on their family or that they felt fine; others had concerns about whether the tests were accurate.
That low number “surprised us,” said Mozersky. “Our study certainly suggests that when you’re really faced with knowing, that your answer is more likely to possibly be no,” she added.
DTC companies tell buyers that results could motivate them to change their lifestyle to reduce their future risk for AD and dementia. But some participants in Mozersky’s study said they didn’t want to know their status because there were no preventive treatments. Test results weren’t seen as “actionable,” she said.
Some studies have shown a degree of fatalism in individuals after receiving a test result, whether it’s positive or negative.
A group of Israeli researchers studied responses of people given PET scans to detect beta-amyloid. Before testing, all participants said they were motivated to adopt lifestyle changes to fight dementia. However, after testing, both those who had elevated beta-amyloid and those who did not reported a much lower desire to change their lifestyle. Those with normal scans probably felt relieved, wrote the researchers. The group with abnormal scans was too small to fully understand their reaction, they wrote.
Concerns about insurance coverage might also deter potential test-takers. Overall, 44% of those responding to the Alzheimer’s Association survey said they were worried that insurers might not cover healthcare costs in the future if they had received a positive test earlier. Respondents also worried about test accuracy, the cost of testing, and whether a positive test might lead to a prohibition on some activities, like driving.
What About the Doctors?
The DTC companies promise buyers that results will be private and won’t be shared with insurers — or with clinicians. And that raises another issue for many who are concerned about the lack of a physician intermediary with at-home testing.
“You remove the opportunity for clinicians to both review the result and figure out how to interpret it before it’s communicated to the patient,” Jalayne J. Arias, JD, a bioethicist and associate professor of Health Policy and Behavioral Sciences at Georgia State University, Atlanta, told this news organization.
Many in the field have been “thinking really carefully about how do we provide guidance to clinicians about biomarker testing,” she said. “Those issues are just heightened when we put it into a direct-to-consumer model,” Arias said.
Arias — who with colleagues published an analysis of potential insurance issues with biomarker tests in JAMA Neurology — said that prohibitions against discrimination based on preexisting conditions means that most likely, health insurers could not use testing data to deny coverage or increase premiums.
But, she said, “there are some question marks around the discrimination risks.” This is especially true for people seeking long-term care, disability or life insurance, she added.
If a test result is not documented in a medical record, it’s not clear whether the individual has an obligation to disclose the result to an insurer, said Arias.
Given all the unanswered questions about how results should be interpreted, to whom the results should be disclosed, and when and how to have discussions with patients, “it’s hard for me to imagine that we’re quite ready for a direct-to-consumer” test, Arias said.
Mozersky noted that Washington University has a financial stake in C2N Diagnostics, which makes the PrecivityAD — biomarker tests for AD. Arias reported having no conflicts of interest.
A version of this article first appeared on Medscape.com.
Given the opportunity, 90% of Americans say they would take a blood biomarker test for Alzheimer’s disease (AD) — even in the absence of symptoms. Notably, 80% say they wouldn’t wait for a physician to order a test, they’d request one themselves.
The findings, from a recent nationwide survey by the Alzheimer’s Association, suggest a growing desire to predict the risk for or show evidence of AD and related dementias with a simple blood test. For consumers with the inclination and the money, that desire can now become reality.
Once limited to research settings or only available via a physician’s order, blood-based diagnostics for specific biomarkers — primarily pTau-217 and beta-amyloid 42/20 — are now offered by at least four companies in the US. Several others sell blood-based “dementia” panels without those biomarkers and screens for apolipoprotein (APOE) genes, including APOE4, a variant that confers a higher risk for AD.
The companies promote testing to all comers, not just those with a family history or concerns about cognitive symptoms. Test prices range from hundreds to thousands of dollars, depending on whether they are included in a company membership, often designed to encourage repeat testing. Blood draws are conducted at home or at certified labs. Buyers don’t need a prescription or to consult with a physician after receiving results.
Knowing results of such tests could be empowering and may encourage people to prepare for their illness, Jessica Mozersky, PhD, assistant professor of medicine at the Bioethics Research Center at Washington University in St. Louis, told this news organization. A direct-to-consumer (DTC) test also eliminates potential physician-created barriers to testing, she added.
But there are also potential harms.
Based on results, individuals may interpret everyday forgetfulness — like misplacing keys — as a sign that dementia is inevitable. This can lead them to change life plans, rethink the way they spend their time, or begin viewing their future negatively. “It creates unnecessary worry and anxiety,” Mozersky said.
The growing availability of DTC tests — heralded by some experts and discouraged by others — comes as AD and dementia specialists continue to debate whether AD diagnostic and staging criteria should be based only on biomarkers or on criteria that includes both pathology and symptomology.
For many, it raises a fundamental concern: If experts haven’t reached a consensus on blood-based AD biomarker testing, how can consumers be expected to interpret at-home test results?
Growing Demand
In 2024, the number of people living with AD passed 7 million. A recent report from the Alzheimer’s Association estimates that number will nearly double by 2060.
The demand for testing also appears to be rising. Similar to the findings in the Alzheimer’s Association’s survey, a small observational study published last year showed that 90% of patients who received a cerebrospinal fluid AD biomarker test ordered by a physician said the decision to get the test was “easy.” For 82%, getting results was positive because it allowed them to plan ahead and to adopt or continue healthy behaviors such as exercise and cognitive activities.
Until now, blood biomarker tests for AD have primarily been available only through a doctor. The tests measure beta-amyloid 42/20 and pTau-217, both of which are strong biomarkers of AD. Some other blood-based biomarkers under investigation include neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).
As reported by Medscape Medical News, the FDA approved the first blood-based AD diagnostic test in May. The Lumipulse G pTau 217/Beta-Amyloid 1-42 is for the early detection of amyloid plaques associated with AD in adults aged 55 years or older who show signs and symptoms of the disease. But it is only available by prescription.
Quest Diagnostics tested the DTC market in 2023, promoting a consumer-initiated test for beta-amyloid 42/40 that had previously been available only through physicians. It was not well-received by clinicians and ethicists. The company withdrew it later that year but continues to sell beta-amyloid 42/20 and pTau-217 tests through physicians, as does its competitor Labcorp.
Today, at least a handful of companies in the US market AD biomarkers directly to the public: Apollo Health, BetterBrain, Function Health, Neurogen Biomarking, and True Health Labs. None of the companies have disclosed ties to pharmaceutical or device companies or test developers.
What Can Consumers Get?
Some companies direct customers to a lab for blood sample collection, whereas others send a technician to customers’ homes. The extent of biomarker testing and posttest consultation also vary by company.
Apollo Health customers can order a “BrainScan” for $799, which includes screens for pTau-217, GFAP, and NfL. Buyers get a detailed report that explains each test, the result (in nanograms per liter) and optimal range (ng/L) and potential next steps. A pTau-217 result in the normal range, for instance, would come with a recommendation for repeat testing every 2 years. If someone receives an abnormal result, they are contacted by a health coach who can make a physician referral.
At Function Health, members pay $499 a year to have access to hundreds of tests and a written summary of results by a clinician. All of its “Brain Health” tests, including “Beta-Amyloid 42/40 Ratio,” pTau-217, APOE, MTHFR, DNA, and NfL, are available for an additional undisclosed charge.
BetterBrain has a $399 membership that covers an initial 75-minute consultation with cognitive tests, a “personalized brain health plan,” and a blood test that is a basic panel without AD biomarkers. A $499 membership includes all of that plus an APOE test. A pTau-217 test is available for an additional undisclosed fee.
At Neurogen Biomarking, which started in January, a consumer orders an at-home test kit, and a phlebotomist comes to their home for a blood draw. The consumer then fills out an online cognitive assessment. Test results are reviewed by a board-certified neurologist and discussed with the consumer via a virtual visit. If the person is at low-risk, they are given some educational material. Those at higher risk are referred to Neurogen’s “team of specialty-trained neurologists” for continuing care. Testing costs were not provided by the company.
Consumers can order “Beta-Amyloid 42/40” for $749 and pTau-217 for $229 directly through True Health Labs. No consultations or services are offered.
DTC Testing Raises Alarms
It’s unclear where DTC tests fall in terms of regulation. The FDA does not usually review at-home tests for low-risk medical purposes but will generally do so for diagnostics that are for higher-risk conditions “to determine the validity of test claims,” according to the agency’s website.
Consumers, however, don’t usually have easy access to information on biomarker tests’ sensitivity, specificity, or other characteristics that would be used by clinicians or regulatory authorities to assess a test’s validity.
The lack of regulation of consumer-initiated AD testing is one issue cited by critics of at-home tests, including the Alzheimer’s Association.
“None of these tests have been scientifically proven to be accurate,” the association noted in a statement, adding that “the tests can have false positive results, meaning that individuals can have results saying they have dementia when in fact they do not.”
“For these and other reasons, the Alzheimer’s Association believes that home screening tests cannot and should not be used as a substitute for a thorough examination by a skilled physician. The whole process of assessment and diagnosis should be carried out within the context of an ongoing relationship with a responsible and qualified healthcare professional,” the statement said.
The association also said that biomarker tests should not be ordered — even by physicians — for asymptomatic individuals.
The American Academy of Neurology (AAN) does not have a position on DTC tests for AD biomarkers, a spokesperson told this news organization. In a 2021 paper on ethical considerations for diagnosis and care, an AAN committee said that biomarker testing could be clinically useful for some symptomatic patients, but testing asymptomatic individuals is “recommended solely in a research setting” because of potential harms “and the absence of interventions capable of favorably altering the natural history of the disease.”
Eric Topol, MD, chair of the Department of Translational Medicine at Scripps Research in La Jolla, California, is bullish on the potential for blood-based biomarker tests. In a blog post, he called the pTau-217 biomarker “one of the most exciting advances in neurology for decades, giving us a new opportunity to accurately predict and potentially prevent (or at least substantially delay) mild cognitive impairment and Alzheimer’s.”
But, wrote Topol, who is the former editor in chief of MedscapeMedical News, “I don’t think these biomarkers are going to be useful in people at low risk.” He wrote that testing should not be used by people who are “cognitively intact” or to tell someone they have pre-AD. “More work needs to be done to determine whether lowering one’s pTau-217 will alter the brain plaque progression and be seen as a disease-modifier,” wrote Topol.
The Risks of Knowing
Some people don’t want to know their biomarker status. In a study in May in JAMA Network Open, Mozersky and colleagues reported that while 81% of a group of cognitively normal participants in a longitudinal study of dementia said they wanted to see results, only 60% ultimately opted to get results after testing. Participants said they did not want to know because they didn’t want to become a burden on their family or that they felt fine; others had concerns about whether the tests were accurate.
That low number “surprised us,” said Mozersky. “Our study certainly suggests that when you’re really faced with knowing, that your answer is more likely to possibly be no,” she added.
DTC companies tell buyers that results could motivate them to change their lifestyle to reduce their future risk for AD and dementia. But some participants in Mozersky’s study said they didn’t want to know their status because there were no preventive treatments. Test results weren’t seen as “actionable,” she said.
Some studies have shown a degree of fatalism in individuals after receiving a test result, whether it’s positive or negative.
A group of Israeli researchers studied responses of people given PET scans to detect beta-amyloid. Before testing, all participants said they were motivated to adopt lifestyle changes to fight dementia. However, after testing, both those who had elevated beta-amyloid and those who did not reported a much lower desire to change their lifestyle. Those with normal scans probably felt relieved, wrote the researchers. The group with abnormal scans was too small to fully understand their reaction, they wrote.
Concerns about insurance coverage might also deter potential test-takers. Overall, 44% of those responding to the Alzheimer’s Association survey said they were worried that insurers might not cover healthcare costs in the future if they had received a positive test earlier. Respondents also worried about test accuracy, the cost of testing, and whether a positive test might lead to a prohibition on some activities, like driving.
What About the Doctors?
The DTC companies promise buyers that results will be private and won’t be shared with insurers — or with clinicians. And that raises another issue for many who are concerned about the lack of a physician intermediary with at-home testing.
“You remove the opportunity for clinicians to both review the result and figure out how to interpret it before it’s communicated to the patient,” Jalayne J. Arias, JD, a bioethicist and associate professor of Health Policy and Behavioral Sciences at Georgia State University, Atlanta, told this news organization.
Many in the field have been “thinking really carefully about how do we provide guidance to clinicians about biomarker testing,” she said. “Those issues are just heightened when we put it into a direct-to-consumer model,” Arias said.
Arias — who with colleagues published an analysis of potential insurance issues with biomarker tests in JAMA Neurology — said that prohibitions against discrimination based on preexisting conditions means that most likely, health insurers could not use testing data to deny coverage or increase premiums.
But, she said, “there are some question marks around the discrimination risks.” This is especially true for people seeking long-term care, disability or life insurance, she added.
If a test result is not documented in a medical record, it’s not clear whether the individual has an obligation to disclose the result to an insurer, said Arias.
Given all the unanswered questions about how results should be interpreted, to whom the results should be disclosed, and when and how to have discussions with patients, “it’s hard for me to imagine that we’re quite ready for a direct-to-consumer” test, Arias said.
Mozersky noted that Washington University has a financial stake in C2N Diagnostics, which makes the PrecivityAD — biomarker tests for AD. Arias reported having no conflicts of interest.
A version of this article first appeared on Medscape.com.
Given the opportunity, 90% of Americans say they would take a blood biomarker test for Alzheimer’s disease (AD) — even in the absence of symptoms. Notably, 80% say they wouldn’t wait for a physician to order a test, they’d request one themselves.
The findings, from a recent nationwide survey by the Alzheimer’s Association, suggest a growing desire to predict the risk for or show evidence of AD and related dementias with a simple blood test. For consumers with the inclination and the money, that desire can now become reality.
Once limited to research settings or only available via a physician’s order, blood-based diagnostics for specific biomarkers — primarily pTau-217 and beta-amyloid 42/20 — are now offered by at least four companies in the US. Several others sell blood-based “dementia” panels without those biomarkers and screens for apolipoprotein (APOE) genes, including APOE4, a variant that confers a higher risk for AD.
The companies promote testing to all comers, not just those with a family history or concerns about cognitive symptoms. Test prices range from hundreds to thousands of dollars, depending on whether they are included in a company membership, often designed to encourage repeat testing. Blood draws are conducted at home or at certified labs. Buyers don’t need a prescription or to consult with a physician after receiving results.
Knowing results of such tests could be empowering and may encourage people to prepare for their illness, Jessica Mozersky, PhD, assistant professor of medicine at the Bioethics Research Center at Washington University in St. Louis, told this news organization. A direct-to-consumer (DTC) test also eliminates potential physician-created barriers to testing, she added.
But there are also potential harms.
Based on results, individuals may interpret everyday forgetfulness — like misplacing keys — as a sign that dementia is inevitable. This can lead them to change life plans, rethink the way they spend their time, or begin viewing their future negatively. “It creates unnecessary worry and anxiety,” Mozersky said.
The growing availability of DTC tests — heralded by some experts and discouraged by others — comes as AD and dementia specialists continue to debate whether AD diagnostic and staging criteria should be based only on biomarkers or on criteria that includes both pathology and symptomology.
For many, it raises a fundamental concern: If experts haven’t reached a consensus on blood-based AD biomarker testing, how can consumers be expected to interpret at-home test results?
Growing Demand
In 2024, the number of people living with AD passed 7 million. A recent report from the Alzheimer’s Association estimates that number will nearly double by 2060.
The demand for testing also appears to be rising. Similar to the findings in the Alzheimer’s Association’s survey, a small observational study published last year showed that 90% of patients who received a cerebrospinal fluid AD biomarker test ordered by a physician said the decision to get the test was “easy.” For 82%, getting results was positive because it allowed them to plan ahead and to adopt or continue healthy behaviors such as exercise and cognitive activities.
Until now, blood biomarker tests for AD have primarily been available only through a doctor. The tests measure beta-amyloid 42/20 and pTau-217, both of which are strong biomarkers of AD. Some other blood-based biomarkers under investigation include neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).
As reported by Medscape Medical News, the FDA approved the first blood-based AD diagnostic test in May. The Lumipulse G pTau 217/Beta-Amyloid 1-42 is for the early detection of amyloid plaques associated with AD in adults aged 55 years or older who show signs and symptoms of the disease. But it is only available by prescription.
Quest Diagnostics tested the DTC market in 2023, promoting a consumer-initiated test for beta-amyloid 42/40 that had previously been available only through physicians. It was not well-received by clinicians and ethicists. The company withdrew it later that year but continues to sell beta-amyloid 42/20 and pTau-217 tests through physicians, as does its competitor Labcorp.
Today, at least a handful of companies in the US market AD biomarkers directly to the public: Apollo Health, BetterBrain, Function Health, Neurogen Biomarking, and True Health Labs. None of the companies have disclosed ties to pharmaceutical or device companies or test developers.
What Can Consumers Get?
Some companies direct customers to a lab for blood sample collection, whereas others send a technician to customers’ homes. The extent of biomarker testing and posttest consultation also vary by company.
Apollo Health customers can order a “BrainScan” for $799, which includes screens for pTau-217, GFAP, and NfL. Buyers get a detailed report that explains each test, the result (in nanograms per liter) and optimal range (ng/L) and potential next steps. A pTau-217 result in the normal range, for instance, would come with a recommendation for repeat testing every 2 years. If someone receives an abnormal result, they are contacted by a health coach who can make a physician referral.
At Function Health, members pay $499 a year to have access to hundreds of tests and a written summary of results by a clinician. All of its “Brain Health” tests, including “Beta-Amyloid 42/40 Ratio,” pTau-217, APOE, MTHFR, DNA, and NfL, are available for an additional undisclosed charge.
BetterBrain has a $399 membership that covers an initial 75-minute consultation with cognitive tests, a “personalized brain health plan,” and a blood test that is a basic panel without AD biomarkers. A $499 membership includes all of that plus an APOE test. A pTau-217 test is available for an additional undisclosed fee.
At Neurogen Biomarking, which started in January, a consumer orders an at-home test kit, and a phlebotomist comes to their home for a blood draw. The consumer then fills out an online cognitive assessment. Test results are reviewed by a board-certified neurologist and discussed with the consumer via a virtual visit. If the person is at low-risk, they are given some educational material. Those at higher risk are referred to Neurogen’s “team of specialty-trained neurologists” for continuing care. Testing costs were not provided by the company.
Consumers can order “Beta-Amyloid 42/40” for $749 and pTau-217 for $229 directly through True Health Labs. No consultations or services are offered.
DTC Testing Raises Alarms
It’s unclear where DTC tests fall in terms of regulation. The FDA does not usually review at-home tests for low-risk medical purposes but will generally do so for diagnostics that are for higher-risk conditions “to determine the validity of test claims,” according to the agency’s website.
Consumers, however, don’t usually have easy access to information on biomarker tests’ sensitivity, specificity, or other characteristics that would be used by clinicians or regulatory authorities to assess a test’s validity.
The lack of regulation of consumer-initiated AD testing is one issue cited by critics of at-home tests, including the Alzheimer’s Association.
“None of these tests have been scientifically proven to be accurate,” the association noted in a statement, adding that “the tests can have false positive results, meaning that individuals can have results saying they have dementia when in fact they do not.”
“For these and other reasons, the Alzheimer’s Association believes that home screening tests cannot and should not be used as a substitute for a thorough examination by a skilled physician. The whole process of assessment and diagnosis should be carried out within the context of an ongoing relationship with a responsible and qualified healthcare professional,” the statement said.
The association also said that biomarker tests should not be ordered — even by physicians — for asymptomatic individuals.
The American Academy of Neurology (AAN) does not have a position on DTC tests for AD biomarkers, a spokesperson told this news organization. In a 2021 paper on ethical considerations for diagnosis and care, an AAN committee said that biomarker testing could be clinically useful for some symptomatic patients, but testing asymptomatic individuals is “recommended solely in a research setting” because of potential harms “and the absence of interventions capable of favorably altering the natural history of the disease.”
Eric Topol, MD, chair of the Department of Translational Medicine at Scripps Research in La Jolla, California, is bullish on the potential for blood-based biomarker tests. In a blog post, he called the pTau-217 biomarker “one of the most exciting advances in neurology for decades, giving us a new opportunity to accurately predict and potentially prevent (or at least substantially delay) mild cognitive impairment and Alzheimer’s.”
But, wrote Topol, who is the former editor in chief of MedscapeMedical News, “I don’t think these biomarkers are going to be useful in people at low risk.” He wrote that testing should not be used by people who are “cognitively intact” or to tell someone they have pre-AD. “More work needs to be done to determine whether lowering one’s pTau-217 will alter the brain plaque progression and be seen as a disease-modifier,” wrote Topol.
The Risks of Knowing
Some people don’t want to know their biomarker status. In a study in May in JAMA Network Open, Mozersky and colleagues reported that while 81% of a group of cognitively normal participants in a longitudinal study of dementia said they wanted to see results, only 60% ultimately opted to get results after testing. Participants said they did not want to know because they didn’t want to become a burden on their family or that they felt fine; others had concerns about whether the tests were accurate.
That low number “surprised us,” said Mozersky. “Our study certainly suggests that when you’re really faced with knowing, that your answer is more likely to possibly be no,” she added.
DTC companies tell buyers that results could motivate them to change their lifestyle to reduce their future risk for AD and dementia. But some participants in Mozersky’s study said they didn’t want to know their status because there were no preventive treatments. Test results weren’t seen as “actionable,” she said.
Some studies have shown a degree of fatalism in individuals after receiving a test result, whether it’s positive or negative.
A group of Israeli researchers studied responses of people given PET scans to detect beta-amyloid. Before testing, all participants said they were motivated to adopt lifestyle changes to fight dementia. However, after testing, both those who had elevated beta-amyloid and those who did not reported a much lower desire to change their lifestyle. Those with normal scans probably felt relieved, wrote the researchers. The group with abnormal scans was too small to fully understand their reaction, they wrote.
Concerns about insurance coverage might also deter potential test-takers. Overall, 44% of those responding to the Alzheimer’s Association survey said they were worried that insurers might not cover healthcare costs in the future if they had received a positive test earlier. Respondents also worried about test accuracy, the cost of testing, and whether a positive test might lead to a prohibition on some activities, like driving.
What About the Doctors?
The DTC companies promise buyers that results will be private and won’t be shared with insurers — or with clinicians. And that raises another issue for many who are concerned about the lack of a physician intermediary with at-home testing.
“You remove the opportunity for clinicians to both review the result and figure out how to interpret it before it’s communicated to the patient,” Jalayne J. Arias, JD, a bioethicist and associate professor of Health Policy and Behavioral Sciences at Georgia State University, Atlanta, told this news organization.
Many in the field have been “thinking really carefully about how do we provide guidance to clinicians about biomarker testing,” she said. “Those issues are just heightened when we put it into a direct-to-consumer model,” Arias said.
Arias — who with colleagues published an analysis of potential insurance issues with biomarker tests in JAMA Neurology — said that prohibitions against discrimination based on preexisting conditions means that most likely, health insurers could not use testing data to deny coverage or increase premiums.
But, she said, “there are some question marks around the discrimination risks.” This is especially true for people seeking long-term care, disability or life insurance, she added.
If a test result is not documented in a medical record, it’s not clear whether the individual has an obligation to disclose the result to an insurer, said Arias.
Given all the unanswered questions about how results should be interpreted, to whom the results should be disclosed, and when and how to have discussions with patients, “it’s hard for me to imagine that we’re quite ready for a direct-to-consumer” test, Arias said.
Mozersky noted that Washington University has a financial stake in C2N Diagnostics, which makes the PrecivityAD — biomarker tests for AD. Arias reported having no conflicts of interest.
A version of this article first appeared on Medscape.com.
Landmark 20-Year Study Reshapes Understanding of PTSD
A large 20-year study — the longest and most detailed of its kind — shows that posttraumatic stress disorder (PTSD) symptoms can endure for decades, challenging conventional timelines for recovery and offering new insights to guide future treatment.
Researchers analyzed data from the World Trade Center Health Program (WTCHP), which is administered by the US CDC’s National Institute for Occupational Safety and Health (NIOSH), and found symptoms of PTSD persisted for as long as two decades in 10% of first responders involved in the World Trade Center disaster of September 2001.
Participation in the WTCHP is voluntary, but those who enroll receive free assessments, monitoring, and treatment, including psychiatric and behavioral healthcare. It is the longest and most detailed analysis of PTSD and includes 81,298 observations from 12,822 WTC responders.
Participants entered the WTCHP at different timepoints and were assessed annually. Not every enrollee was assessed every year, but the sheer number of participants and observations “just provides much greater density of data over that 20-year course than any previous study,” lead author Frank D. Mann, PhD, told this news organization.
The study was published online on May 27 in Nature Mental Health.
Filling the PTSD Knowledge Gap
Most PTSD research has focused on the short term, with limited insight into how symptoms evolve over the long haul. Without long-term data, it’s been difficult to understand whether PTSD resolves, persists, or worsens — hindering efforts to guide treatment and support. This study aimed to fill that gap by tracking symptom patterns over two decades.
Responders were assessed regularly using the PTSD Checklist for a Specific Stressor, a standardized tool that measures symptom severity on an 85-point scale. On average, each participant completed 6.3 assessments over the course of the study.
A score of ≥ 44 was considered indicative of clinically elevated PTSD symptoms. Between 2002 and 2022, the crude prevalence of elevated symptoms ranged from 8% to 15%. At the same time, 16% to 34% of responders each year reported little to no symptoms, scoring at or near the minimum on the scale.
The researchers found that symptom trajectories varied widely. Nearly as many participants experienced worsening symptoms as those who improved. As a result, the overall population average remained relatively flat over the 20-year period.
Among responders who met the threshold for PTSD, the median time to symptom improvement was 8.9 years — and by year 20, about 76% had shown improvement.
New Insights
Mann, a senior research scientist at Stony Brook University Renaissance School of Medicine, Stony Brook, New York, said the study not only reinforced existing knowledge about PTSD in responders but also uncovered new insights.
Most notably, it showed that PTSD symptoms tended to peak around a decade after 9/11 — significantly later than delayed-onset patterns reported in previous trauma studies.
He also noted a surprising outcome — the top 10% of responders who experienced worsening symptoms over the long term accounted for the majority of mental health costs. These individuals, Mann said, represent a critical gap in care, with current interventions proving largely ineffective for them.
Mann suggested that ongoing trauma exposure — especially for responders still in high-risk jobs — and potential genetic susceptibility may contribute to late-emerging or persistent symptoms.
“These individuals are an urgent priority for health systems, as available resources have not been effective for them,” the study authors wrote.
Mann and his colleagues also found that occupation offered the strongest protection against developing PTSD. Police officers and firefighters benefit from training designed to help them cope with trauma, and repeated exposure may build a degree of resilience.
In contrast, responders without such training — like construction workers — faced a 50% to 55% higher risk of developing PTSD symptoms. Mann emphasized that occupational status was a more powerful predictor of PTSD risk than the severity of the traumatic exposures themselves.
A Valuable Contribution
Commenting on the research for this news organization, Sandra Lowe, MD, medical director of the Mount Sinai WTCMH program, noted that while the study largely confirms what has been known about responders — such as the significant variability in symptom trajectories over time — it still makes a valuable contribution.
“Extending observations for up to 20 years is rare in any study, especially in a cohort this large,” said Lowe, an associate professor of psychiatry at the Icahn School of Medicine at Mount Sinai, New York City, who was not involved in the study.
Also commenting, James West, MD, chair of the American Psychiatric Association’s Committee on the Psychiatric Dimensions of Disaster, described the finding that 10% of responders continued to experience symptoms two decades after exposure as “sobering.”
However, he emphasized that it aligns with observations in the disaster recovery community, where the psychological impact “goes way beyond what most people see as the immediate aftermath and recovery.” West stressed the urgent need to develop effective treatments that enable those affected to live fuller, less impaired lives.
“We still need to be finding the effective treatments that can help these people live fuller lives without impairment from their trauma symptoms,” said West.
Lowe pointed out that the symptom peak around 10 years post-exposure is often linked to external factors. Some responders who had been managing symptoms might lose resilience due to major life changes such as retirement.
“One of the things that was able to keep them engaged is now lost,” she said. “They begin to spend more time reflecting on recollections, and symptoms can worsen.”
West agreed, adding that retirement or job loss often leads to symptom increases because it removes a primary coping mechanism. Both Lowe and Mann also highlighted that 9/11 memorial events can trigger new symptoms or exacerbate existing ones.
Lowe noted that responders with stronger coping skills tended to fare better over time. Effective coping strategies include maintaining regular schedules — especially for eating and sleeping — leading a structured life, and employing stress management techniques like meditation, yoga, or enjoyable hobbies. Social connection and being part of a community are also critical for resilience. She added that clinicians should always inquire about trauma history.
Lowe, West, and Mann all pointed out that PTSD is often accompanied by physical health issues, particularly cardiovascular problems, which tend to be worse in those with the disorder.
Responders with stronger coping skills tended to do better over time, said Lowe. Coping skills that can help make a difference include having a regular schedule, especially for eating and sleeping; having a structured life; and stress management tools, such as meditation or yoga or an enjoyable hobby. Social connection — being part of a community — is also critical, Lowe said.
Clinicians should always inquire about trauma, she said. Lowe, West, and Mann all noted that people with PTSD often have physical illness and that cardiovascular outcomes in particular are worse for those individuals.
WTCHP Future Uncertain
However, despite advances in understanding PTSD and the importance of ongoing care, the future of the program supporting World Trade Center responders remains uncertain.
Some 140,000 people are now enrolled in the WTCHP, which was established as a federal program in 2010. Congress has generally reauthorized the program whenever its funding came up for renewal.
However, earlier this year, the Trump administration dismissed two thirds of the NIOSH workforce, including John Howard, MD, the administrator of the WTCHP.
In response, members of Congress and advocates for 9/11 survivors urged the US Department of Health and Human Services (HHS) to reinstate Howard and the affected employees. Howard is listed as back on the job has since returned to his position, and HHS reportedly reinstated hundreds of NIOSH workers in May.
An HHS spokesperson told this news organization that the WTCHP continues to provide services and is actively “accepting, reviewing, and processing new enrollment applications and certification requests.”
Meanwhile, the Trump administration’s fiscal year 2026 budget proposal seeks to reduce CDC funding by $3.5 billion — approximately 40% — with a shift in focus toward infectious diseases. It remains unclear how the WTCHP will be affected by this new direction.
Mann said he is not involved in the program’s funding details but added, “Presumably, as long as some funding continues to keep the program alive, we will continue monitoring responders and providing free treatment until the very last World Trade Center responder passes.”
The study was partially funded through National Institutes of Health and CDC grants, the SUNY Research Foundation, and the CDC’s World Trade Center Health Program. Mann, Lowe, and West reported having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A large 20-year study — the longest and most detailed of its kind — shows that posttraumatic stress disorder (PTSD) symptoms can endure for decades, challenging conventional timelines for recovery and offering new insights to guide future treatment.
Researchers analyzed data from the World Trade Center Health Program (WTCHP), which is administered by the US CDC’s National Institute for Occupational Safety and Health (NIOSH), and found symptoms of PTSD persisted for as long as two decades in 10% of first responders involved in the World Trade Center disaster of September 2001.
Participation in the WTCHP is voluntary, but those who enroll receive free assessments, monitoring, and treatment, including psychiatric and behavioral healthcare. It is the longest and most detailed analysis of PTSD and includes 81,298 observations from 12,822 WTC responders.
Participants entered the WTCHP at different timepoints and were assessed annually. Not every enrollee was assessed every year, but the sheer number of participants and observations “just provides much greater density of data over that 20-year course than any previous study,” lead author Frank D. Mann, PhD, told this news organization.
The study was published online on May 27 in Nature Mental Health.
Filling the PTSD Knowledge Gap
Most PTSD research has focused on the short term, with limited insight into how symptoms evolve over the long haul. Without long-term data, it’s been difficult to understand whether PTSD resolves, persists, or worsens — hindering efforts to guide treatment and support. This study aimed to fill that gap by tracking symptom patterns over two decades.
Responders were assessed regularly using the PTSD Checklist for a Specific Stressor, a standardized tool that measures symptom severity on an 85-point scale. On average, each participant completed 6.3 assessments over the course of the study.
A score of ≥ 44 was considered indicative of clinically elevated PTSD symptoms. Between 2002 and 2022, the crude prevalence of elevated symptoms ranged from 8% to 15%. At the same time, 16% to 34% of responders each year reported little to no symptoms, scoring at or near the minimum on the scale.
The researchers found that symptom trajectories varied widely. Nearly as many participants experienced worsening symptoms as those who improved. As a result, the overall population average remained relatively flat over the 20-year period.
Among responders who met the threshold for PTSD, the median time to symptom improvement was 8.9 years — and by year 20, about 76% had shown improvement.
New Insights
Mann, a senior research scientist at Stony Brook University Renaissance School of Medicine, Stony Brook, New York, said the study not only reinforced existing knowledge about PTSD in responders but also uncovered new insights.
Most notably, it showed that PTSD symptoms tended to peak around a decade after 9/11 — significantly later than delayed-onset patterns reported in previous trauma studies.
He also noted a surprising outcome — the top 10% of responders who experienced worsening symptoms over the long term accounted for the majority of mental health costs. These individuals, Mann said, represent a critical gap in care, with current interventions proving largely ineffective for them.
Mann suggested that ongoing trauma exposure — especially for responders still in high-risk jobs — and potential genetic susceptibility may contribute to late-emerging or persistent symptoms.
“These individuals are an urgent priority for health systems, as available resources have not been effective for them,” the study authors wrote.
Mann and his colleagues also found that occupation offered the strongest protection against developing PTSD. Police officers and firefighters benefit from training designed to help them cope with trauma, and repeated exposure may build a degree of resilience.
In contrast, responders without such training — like construction workers — faced a 50% to 55% higher risk of developing PTSD symptoms. Mann emphasized that occupational status was a more powerful predictor of PTSD risk than the severity of the traumatic exposures themselves.
A Valuable Contribution
Commenting on the research for this news organization, Sandra Lowe, MD, medical director of the Mount Sinai WTCMH program, noted that while the study largely confirms what has been known about responders — such as the significant variability in symptom trajectories over time — it still makes a valuable contribution.
“Extending observations for up to 20 years is rare in any study, especially in a cohort this large,” said Lowe, an associate professor of psychiatry at the Icahn School of Medicine at Mount Sinai, New York City, who was not involved in the study.
Also commenting, James West, MD, chair of the American Psychiatric Association’s Committee on the Psychiatric Dimensions of Disaster, described the finding that 10% of responders continued to experience symptoms two decades after exposure as “sobering.”
However, he emphasized that it aligns with observations in the disaster recovery community, where the psychological impact “goes way beyond what most people see as the immediate aftermath and recovery.” West stressed the urgent need to develop effective treatments that enable those affected to live fuller, less impaired lives.
“We still need to be finding the effective treatments that can help these people live fuller lives without impairment from their trauma symptoms,” said West.
Lowe pointed out that the symptom peak around 10 years post-exposure is often linked to external factors. Some responders who had been managing symptoms might lose resilience due to major life changes such as retirement.
“One of the things that was able to keep them engaged is now lost,” she said. “They begin to spend more time reflecting on recollections, and symptoms can worsen.”
West agreed, adding that retirement or job loss often leads to symptom increases because it removes a primary coping mechanism. Both Lowe and Mann also highlighted that 9/11 memorial events can trigger new symptoms or exacerbate existing ones.
Lowe noted that responders with stronger coping skills tended to fare better over time. Effective coping strategies include maintaining regular schedules — especially for eating and sleeping — leading a structured life, and employing stress management techniques like meditation, yoga, or enjoyable hobbies. Social connection and being part of a community are also critical for resilience. She added that clinicians should always inquire about trauma history.
Lowe, West, and Mann all pointed out that PTSD is often accompanied by physical health issues, particularly cardiovascular problems, which tend to be worse in those with the disorder.
Responders with stronger coping skills tended to do better over time, said Lowe. Coping skills that can help make a difference include having a regular schedule, especially for eating and sleeping; having a structured life; and stress management tools, such as meditation or yoga or an enjoyable hobby. Social connection — being part of a community — is also critical, Lowe said.
Clinicians should always inquire about trauma, she said. Lowe, West, and Mann all noted that people with PTSD often have physical illness and that cardiovascular outcomes in particular are worse for those individuals.
WTCHP Future Uncertain
However, despite advances in understanding PTSD and the importance of ongoing care, the future of the program supporting World Trade Center responders remains uncertain.
Some 140,000 people are now enrolled in the WTCHP, which was established as a federal program in 2010. Congress has generally reauthorized the program whenever its funding came up for renewal.
However, earlier this year, the Trump administration dismissed two thirds of the NIOSH workforce, including John Howard, MD, the administrator of the WTCHP.
In response, members of Congress and advocates for 9/11 survivors urged the US Department of Health and Human Services (HHS) to reinstate Howard and the affected employees. Howard is listed as back on the job has since returned to his position, and HHS reportedly reinstated hundreds of NIOSH workers in May.
An HHS spokesperson told this news organization that the WTCHP continues to provide services and is actively “accepting, reviewing, and processing new enrollment applications and certification requests.”
Meanwhile, the Trump administration’s fiscal year 2026 budget proposal seeks to reduce CDC funding by $3.5 billion — approximately 40% — with a shift in focus toward infectious diseases. It remains unclear how the WTCHP will be affected by this new direction.
Mann said he is not involved in the program’s funding details but added, “Presumably, as long as some funding continues to keep the program alive, we will continue monitoring responders and providing free treatment until the very last World Trade Center responder passes.”
The study was partially funded through National Institutes of Health and CDC grants, the SUNY Research Foundation, and the CDC’s World Trade Center Health Program. Mann, Lowe, and West reported having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A large 20-year study — the longest and most detailed of its kind — shows that posttraumatic stress disorder (PTSD) symptoms can endure for decades, challenging conventional timelines for recovery and offering new insights to guide future treatment.
Researchers analyzed data from the World Trade Center Health Program (WTCHP), which is administered by the US CDC’s National Institute for Occupational Safety and Health (NIOSH), and found symptoms of PTSD persisted for as long as two decades in 10% of first responders involved in the World Trade Center disaster of September 2001.
Participation in the WTCHP is voluntary, but those who enroll receive free assessments, monitoring, and treatment, including psychiatric and behavioral healthcare. It is the longest and most detailed analysis of PTSD and includes 81,298 observations from 12,822 WTC responders.
Participants entered the WTCHP at different timepoints and were assessed annually. Not every enrollee was assessed every year, but the sheer number of participants and observations “just provides much greater density of data over that 20-year course than any previous study,” lead author Frank D. Mann, PhD, told this news organization.
The study was published online on May 27 in Nature Mental Health.
Filling the PTSD Knowledge Gap
Most PTSD research has focused on the short term, with limited insight into how symptoms evolve over the long haul. Without long-term data, it’s been difficult to understand whether PTSD resolves, persists, or worsens — hindering efforts to guide treatment and support. This study aimed to fill that gap by tracking symptom patterns over two decades.
Responders were assessed regularly using the PTSD Checklist for a Specific Stressor, a standardized tool that measures symptom severity on an 85-point scale. On average, each participant completed 6.3 assessments over the course of the study.
A score of ≥ 44 was considered indicative of clinically elevated PTSD symptoms. Between 2002 and 2022, the crude prevalence of elevated symptoms ranged from 8% to 15%. At the same time, 16% to 34% of responders each year reported little to no symptoms, scoring at or near the minimum on the scale.
The researchers found that symptom trajectories varied widely. Nearly as many participants experienced worsening symptoms as those who improved. As a result, the overall population average remained relatively flat over the 20-year period.
Among responders who met the threshold for PTSD, the median time to symptom improvement was 8.9 years — and by year 20, about 76% had shown improvement.
New Insights
Mann, a senior research scientist at Stony Brook University Renaissance School of Medicine, Stony Brook, New York, said the study not only reinforced existing knowledge about PTSD in responders but also uncovered new insights.
Most notably, it showed that PTSD symptoms tended to peak around a decade after 9/11 — significantly later than delayed-onset patterns reported in previous trauma studies.
He also noted a surprising outcome — the top 10% of responders who experienced worsening symptoms over the long term accounted for the majority of mental health costs. These individuals, Mann said, represent a critical gap in care, with current interventions proving largely ineffective for them.
Mann suggested that ongoing trauma exposure — especially for responders still in high-risk jobs — and potential genetic susceptibility may contribute to late-emerging or persistent symptoms.
“These individuals are an urgent priority for health systems, as available resources have not been effective for them,” the study authors wrote.
Mann and his colleagues also found that occupation offered the strongest protection against developing PTSD. Police officers and firefighters benefit from training designed to help them cope with trauma, and repeated exposure may build a degree of resilience.
In contrast, responders without such training — like construction workers — faced a 50% to 55% higher risk of developing PTSD symptoms. Mann emphasized that occupational status was a more powerful predictor of PTSD risk than the severity of the traumatic exposures themselves.
A Valuable Contribution
Commenting on the research for this news organization, Sandra Lowe, MD, medical director of the Mount Sinai WTCMH program, noted that while the study largely confirms what has been known about responders — such as the significant variability in symptom trajectories over time — it still makes a valuable contribution.
“Extending observations for up to 20 years is rare in any study, especially in a cohort this large,” said Lowe, an associate professor of psychiatry at the Icahn School of Medicine at Mount Sinai, New York City, who was not involved in the study.
Also commenting, James West, MD, chair of the American Psychiatric Association’s Committee on the Psychiatric Dimensions of Disaster, described the finding that 10% of responders continued to experience symptoms two decades after exposure as “sobering.”
However, he emphasized that it aligns with observations in the disaster recovery community, where the psychological impact “goes way beyond what most people see as the immediate aftermath and recovery.” West stressed the urgent need to develop effective treatments that enable those affected to live fuller, less impaired lives.
“We still need to be finding the effective treatments that can help these people live fuller lives without impairment from their trauma symptoms,” said West.
Lowe pointed out that the symptom peak around 10 years post-exposure is often linked to external factors. Some responders who had been managing symptoms might lose resilience due to major life changes such as retirement.
“One of the things that was able to keep them engaged is now lost,” she said. “They begin to spend more time reflecting on recollections, and symptoms can worsen.”
West agreed, adding that retirement or job loss often leads to symptom increases because it removes a primary coping mechanism. Both Lowe and Mann also highlighted that 9/11 memorial events can trigger new symptoms or exacerbate existing ones.
Lowe noted that responders with stronger coping skills tended to fare better over time. Effective coping strategies include maintaining regular schedules — especially for eating and sleeping — leading a structured life, and employing stress management techniques like meditation, yoga, or enjoyable hobbies. Social connection and being part of a community are also critical for resilience. She added that clinicians should always inquire about trauma history.
Lowe, West, and Mann all pointed out that PTSD is often accompanied by physical health issues, particularly cardiovascular problems, which tend to be worse in those with the disorder.
Responders with stronger coping skills tended to do better over time, said Lowe. Coping skills that can help make a difference include having a regular schedule, especially for eating and sleeping; having a structured life; and stress management tools, such as meditation or yoga or an enjoyable hobby. Social connection — being part of a community — is also critical, Lowe said.
Clinicians should always inquire about trauma, she said. Lowe, West, and Mann all noted that people with PTSD often have physical illness and that cardiovascular outcomes in particular are worse for those individuals.
WTCHP Future Uncertain
However, despite advances in understanding PTSD and the importance of ongoing care, the future of the program supporting World Trade Center responders remains uncertain.
Some 140,000 people are now enrolled in the WTCHP, which was established as a federal program in 2010. Congress has generally reauthorized the program whenever its funding came up for renewal.
However, earlier this year, the Trump administration dismissed two thirds of the NIOSH workforce, including John Howard, MD, the administrator of the WTCHP.
In response, members of Congress and advocates for 9/11 survivors urged the US Department of Health and Human Services (HHS) to reinstate Howard and the affected employees. Howard is listed as back on the job has since returned to his position, and HHS reportedly reinstated hundreds of NIOSH workers in May.
An HHS spokesperson told this news organization that the WTCHP continues to provide services and is actively “accepting, reviewing, and processing new enrollment applications and certification requests.”
Meanwhile, the Trump administration’s fiscal year 2026 budget proposal seeks to reduce CDC funding by $3.5 billion — approximately 40% — with a shift in focus toward infectious diseases. It remains unclear how the WTCHP will be affected by this new direction.
Mann said he is not involved in the program’s funding details but added, “Presumably, as long as some funding continues to keep the program alive, we will continue monitoring responders and providing free treatment until the very last World Trade Center responder passes.”
The study was partially funded through National Institutes of Health and CDC grants, the SUNY Research Foundation, and the CDC’s World Trade Center Health Program. Mann, Lowe, and West reported having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE MENTAL HEALTH
Colonoscopy Screening Effective in 45- to 49-Year-Olds
Researchers at Kaiser Permanente Northern California sought to compare yields between the two age groups to assess how a change in guidance in 2021 urging screening in the younger cohort was borne out in a real-world setting.
The researchers published their findings in JAMA, concluding that the results supported screening colonoscopy in 45- to 49-year-olds.
The study compared 4380 individuals aged 45-49 years, with 7651 who were aged 50-54. All of them underwent their first colonoscopy during 2021 to 2024. Thirty-five percent of the younger group and 40% of the older group had any adenoma.
About 4% of each group had an advanced adenoma, 10% had any sessile serrated lesion, a little under 2% had an advanced serrated lesion, and 0.1% in each group had colorectal cancer.
There were no significant differences in neoplasia prevalence between the groups by sex. The authors did note that the study group included more Asian individuals (30%) than in the general population.
Swati G. Patel, MD, MS, director of the Gastrointestinal Hereditary Cancer Program at the University of Colorado Anschutz Medical Center, Denver, said the Kaiser study is important because its data was aggregated after the US Preventive Services Task Force lowered the screening age in 2021.
The Kaiser research “validates the initial studies” done to support that recommendation and the 2022 consensus statement by the US Multi-Society Task Force on Colorectal Cancer, which also advocated screening in 45- to 49-year-olds.
Even though the new JAMA study found a similar rate of cancers and precursor lesions as in previous trials, it provides “reinforcement of the rationale for decreasing the screening age,” Patel, the lead author on the consensus statement, told GI & Hepatology News.
The Kaiser research is “really powerful information,” she said.
“It certainly validates our current guidance to start screening for colorectal cancer at age 45,” said Audrey Calderwood, MD, director of the GI Cancer Risk and Prevention Clinic at the Geisel School of Medicine, Dartmouth, New Hampshire.
The Kaiser data provides granular information to share with younger patients who might think that they don’t need screening because they are healthy and don’t have symptoms, said Calderwood, also director of the Comprehensive Gastroenterology Center at Dartmouth Hitchcock Medical Center.
Colon cancer rates for Americans under age 50 have been steadily rising for the past decade, hitting about 10 cases per 100,000 in 2022, according to the National Cancer Institute (NCI). In 2023, about 73% of eligible 50- to 75-year-olds received colorectal cancer screening based on the most recent guidelines, according to the NCI.
But screening rates in the under-50 age group are much lower. Researchers estimated in a study that only about 34.5% of those aged 45-49 received colorectal cancer screening, which included colonoscopy, stool-based tests, and CT colonography.
Patel said that estimate is “spot on” in terms of other estimates.
“I think there’s a perception that it’s a cancer of older adults and that young healthy people don’t need to worry about it,” she said, adding that getting the word out to younger Americans is a “PR challenge,” in part because of squeamishness about discussing anything to do with stool and changes in how they access information.
Calderwood agreed. Younger people “aren’t chatting to their friends about” colon cancer screening the way they might about mammography, said Calderwood.
Both she and Patel noted that educating the public was an ongoing project, but that a physician’s recommendation was key.
Patel said she hoped that data provided in the Kaiser study might help “dismantle the systemic skepticism around decreasing the age recommendation” for screening.
Calderwood and Patel reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers at Kaiser Permanente Northern California sought to compare yields between the two age groups to assess how a change in guidance in 2021 urging screening in the younger cohort was borne out in a real-world setting.
The researchers published their findings in JAMA, concluding that the results supported screening colonoscopy in 45- to 49-year-olds.
The study compared 4380 individuals aged 45-49 years, with 7651 who were aged 50-54. All of them underwent their first colonoscopy during 2021 to 2024. Thirty-five percent of the younger group and 40% of the older group had any adenoma.
About 4% of each group had an advanced adenoma, 10% had any sessile serrated lesion, a little under 2% had an advanced serrated lesion, and 0.1% in each group had colorectal cancer.
There were no significant differences in neoplasia prevalence between the groups by sex. The authors did note that the study group included more Asian individuals (30%) than in the general population.
Swati G. Patel, MD, MS, director of the Gastrointestinal Hereditary Cancer Program at the University of Colorado Anschutz Medical Center, Denver, said the Kaiser study is important because its data was aggregated after the US Preventive Services Task Force lowered the screening age in 2021.
The Kaiser research “validates the initial studies” done to support that recommendation and the 2022 consensus statement by the US Multi-Society Task Force on Colorectal Cancer, which also advocated screening in 45- to 49-year-olds.
Even though the new JAMA study found a similar rate of cancers and precursor lesions as in previous trials, it provides “reinforcement of the rationale for decreasing the screening age,” Patel, the lead author on the consensus statement, told GI & Hepatology News.
The Kaiser research is “really powerful information,” she said.
“It certainly validates our current guidance to start screening for colorectal cancer at age 45,” said Audrey Calderwood, MD, director of the GI Cancer Risk and Prevention Clinic at the Geisel School of Medicine, Dartmouth, New Hampshire.
The Kaiser data provides granular information to share with younger patients who might think that they don’t need screening because they are healthy and don’t have symptoms, said Calderwood, also director of the Comprehensive Gastroenterology Center at Dartmouth Hitchcock Medical Center.
Colon cancer rates for Americans under age 50 have been steadily rising for the past decade, hitting about 10 cases per 100,000 in 2022, according to the National Cancer Institute (NCI). In 2023, about 73% of eligible 50- to 75-year-olds received colorectal cancer screening based on the most recent guidelines, according to the NCI.
But screening rates in the under-50 age group are much lower. Researchers estimated in a study that only about 34.5% of those aged 45-49 received colorectal cancer screening, which included colonoscopy, stool-based tests, and CT colonography.
Patel said that estimate is “spot on” in terms of other estimates.
“I think there’s a perception that it’s a cancer of older adults and that young healthy people don’t need to worry about it,” she said, adding that getting the word out to younger Americans is a “PR challenge,” in part because of squeamishness about discussing anything to do with stool and changes in how they access information.
Calderwood agreed. Younger people “aren’t chatting to their friends about” colon cancer screening the way they might about mammography, said Calderwood.
Both she and Patel noted that educating the public was an ongoing project, but that a physician’s recommendation was key.
Patel said she hoped that data provided in the Kaiser study might help “dismantle the systemic skepticism around decreasing the age recommendation” for screening.
Calderwood and Patel reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers at Kaiser Permanente Northern California sought to compare yields between the two age groups to assess how a change in guidance in 2021 urging screening in the younger cohort was borne out in a real-world setting.
The researchers published their findings in JAMA, concluding that the results supported screening colonoscopy in 45- to 49-year-olds.
The study compared 4380 individuals aged 45-49 years, with 7651 who were aged 50-54. All of them underwent their first colonoscopy during 2021 to 2024. Thirty-five percent of the younger group and 40% of the older group had any adenoma.
About 4% of each group had an advanced adenoma, 10% had any sessile serrated lesion, a little under 2% had an advanced serrated lesion, and 0.1% in each group had colorectal cancer.
There were no significant differences in neoplasia prevalence between the groups by sex. The authors did note that the study group included more Asian individuals (30%) than in the general population.
Swati G. Patel, MD, MS, director of the Gastrointestinal Hereditary Cancer Program at the University of Colorado Anschutz Medical Center, Denver, said the Kaiser study is important because its data was aggregated after the US Preventive Services Task Force lowered the screening age in 2021.
The Kaiser research “validates the initial studies” done to support that recommendation and the 2022 consensus statement by the US Multi-Society Task Force on Colorectal Cancer, which also advocated screening in 45- to 49-year-olds.
Even though the new JAMA study found a similar rate of cancers and precursor lesions as in previous trials, it provides “reinforcement of the rationale for decreasing the screening age,” Patel, the lead author on the consensus statement, told GI & Hepatology News.
The Kaiser research is “really powerful information,” she said.
“It certainly validates our current guidance to start screening for colorectal cancer at age 45,” said Audrey Calderwood, MD, director of the GI Cancer Risk and Prevention Clinic at the Geisel School of Medicine, Dartmouth, New Hampshire.
The Kaiser data provides granular information to share with younger patients who might think that they don’t need screening because they are healthy and don’t have symptoms, said Calderwood, also director of the Comprehensive Gastroenterology Center at Dartmouth Hitchcock Medical Center.
Colon cancer rates for Americans under age 50 have been steadily rising for the past decade, hitting about 10 cases per 100,000 in 2022, according to the National Cancer Institute (NCI). In 2023, about 73% of eligible 50- to 75-year-olds received colorectal cancer screening based on the most recent guidelines, according to the NCI.
But screening rates in the under-50 age group are much lower. Researchers estimated in a study that only about 34.5% of those aged 45-49 received colorectal cancer screening, which included colonoscopy, stool-based tests, and CT colonography.
Patel said that estimate is “spot on” in terms of other estimates.
“I think there’s a perception that it’s a cancer of older adults and that young healthy people don’t need to worry about it,” she said, adding that getting the word out to younger Americans is a “PR challenge,” in part because of squeamishness about discussing anything to do with stool and changes in how they access information.
Calderwood agreed. Younger people “aren’t chatting to their friends about” colon cancer screening the way they might about mammography, said Calderwood.
Both she and Patel noted that educating the public was an ongoing project, but that a physician’s recommendation was key.
Patel said she hoped that data provided in the Kaiser study might help “dismantle the systemic skepticism around decreasing the age recommendation” for screening.
Calderwood and Patel reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
New Proposed Health Cybersecurity Rule: What Physicians Should Know
A new federal rule could force hospitals and doctors’ groups to boost health cybersecurity measures to better protect patients’ health information and prevent ransomware attacks.
The proposed rule, issued by the US Department of Health & Human Services (HHS) and published on January 6 in the Federal Register, marks the first time in a decade that the federal government has updated regulations governing the security of private health information (PHI) that’s kept or shared online. Comments on the rule are due on March 6.
Because the risks for cyberattacks have increased exponentially, “there is a greater need to invest than ever before in both people and technologies to secure patient information,” Adam Greene, an attorney at Davis Wright Tremaine in Washington, DC, who advises healthcare clients on cybersecurity, said in an interview.
Bad actors continue to evolve and are often far ahead of their targets, added Mark Fox, privacy and research compliance officer for the American College of Cardiology.
In the proposed rule, HHS noted that breaches have risen by more than 50% since 2020. Damages from health data breaches are more expensive than in any other sector, averaging $10 million per incident, said HHS.
The damage can continue for years, as much of the data — such as date of birth — in PHI are “immutable,” unlike a credit card number, the agency said. A review of breach reports made to HHS’ Office for Civil Rights shows near-daily data breaches affecting hundreds to tens of thousands of patients. Since December 1 alone, healthcare providers reported breaches affecting nearly 3 million US patients, according to federal data.
Debi Carr, a Florida-based cybersecurity consultant for small physician and dental practices, welcomed the new proposal. “Many practices are clinging to doing things the way they have always done it, and hackers are taking full advantage of that mindset,” she said in an interview. “We have to change our mindset.”
Among the proposal’s recommendations:
- A shift away from making security specifications “addressable” to required. Fox said that many interpreted addressable to mean optional. The clarification is important. The government will require greater accountability, including a requirement to annually revise the risk analysis, to review policies and procedures and implementation, and to perform penetration testing, said Greene.
- Requiring multifactor authentication (MFA) and encryption of PHI at rest and in transit. “A reasonable person who does security will tell you that should be a requirement,” said Fox. Carr added that the February 2024 Change Healthcare ransomware attack happened because workers at the payment processing company were not using MFA.
- Requiring all entities to verify at least once a year that “business associates” have put into place the required safeguards; the associates would need to provide a written analysis of relevant electronic information systems by a subject matter expert and a written certification that the analysis has been performed and is accurate. In the past, the rule “only required that you sign a business associate agreement” with the associate, which could be a payer, a pharmacy, or another physician practice, said Fox. The rule would require all entities to get certification that the controls are in place.
- Requiring a detailed map of an electronic network. For a physician practice, that means creating an inventory of all the technology assets, including devices, applications, and anything that would touch electronic PHI, and then creating a map of how it comes into the office, flows through it, and departs, said Greene.
- Having a plan of action in the case of a breach. The rule will require written procedures to restore certain relevant systems and data within 72 hours and written incident response plans.
Some physician practices — especially those still relying on passwords instead of more sophisticated MFA or encryption — may have to invest significantly to strengthen their information security, said Greene. Smaller organizations, for example, may need to upgrade systems to ensure that user access is terminated within an hour after someone’s employment ends.
Carr said practices should not view the investments as a burden. The regulation “will force practices to implement best cybersecurity practices,” she said.
Implementing those best practices serves as insurance, said Fox. He suggests that anyone in doubt “talk to someone who’s actually lived through a breach and had to recover.”
Tampa General Hospital in Florida, for instance, recently settled a class action suit, agreeing to pay $6.8 million to patients whose PHI was compromised.
It is not certain whether or when the health cybersecurity rule will be made final.
The incoming Trump administration could cancel or delay the rulemaking process.
Even if it continues, “I would not expect a final rule in 2025,” said Greene. He estimates that the rule would not take effect until at least 2026; healthcare entities would have 180 days to comply. Still, those 180 days can go by fast.
“I would say don’t panic, but don’t ignore it either,” he said.
A version of this article first appeared on Medscape.com.
A new federal rule could force hospitals and doctors’ groups to boost health cybersecurity measures to better protect patients’ health information and prevent ransomware attacks.
The proposed rule, issued by the US Department of Health & Human Services (HHS) and published on January 6 in the Federal Register, marks the first time in a decade that the federal government has updated regulations governing the security of private health information (PHI) that’s kept or shared online. Comments on the rule are due on March 6.
Because the risks for cyberattacks have increased exponentially, “there is a greater need to invest than ever before in both people and technologies to secure patient information,” Adam Greene, an attorney at Davis Wright Tremaine in Washington, DC, who advises healthcare clients on cybersecurity, said in an interview.
Bad actors continue to evolve and are often far ahead of their targets, added Mark Fox, privacy and research compliance officer for the American College of Cardiology.
In the proposed rule, HHS noted that breaches have risen by more than 50% since 2020. Damages from health data breaches are more expensive than in any other sector, averaging $10 million per incident, said HHS.
The damage can continue for years, as much of the data — such as date of birth — in PHI are “immutable,” unlike a credit card number, the agency said. A review of breach reports made to HHS’ Office for Civil Rights shows near-daily data breaches affecting hundreds to tens of thousands of patients. Since December 1 alone, healthcare providers reported breaches affecting nearly 3 million US patients, according to federal data.
Debi Carr, a Florida-based cybersecurity consultant for small physician and dental practices, welcomed the new proposal. “Many practices are clinging to doing things the way they have always done it, and hackers are taking full advantage of that mindset,” she said in an interview. “We have to change our mindset.”
Among the proposal’s recommendations:
- A shift away from making security specifications “addressable” to required. Fox said that many interpreted addressable to mean optional. The clarification is important. The government will require greater accountability, including a requirement to annually revise the risk analysis, to review policies and procedures and implementation, and to perform penetration testing, said Greene.
- Requiring multifactor authentication (MFA) and encryption of PHI at rest and in transit. “A reasonable person who does security will tell you that should be a requirement,” said Fox. Carr added that the February 2024 Change Healthcare ransomware attack happened because workers at the payment processing company were not using MFA.
- Requiring all entities to verify at least once a year that “business associates” have put into place the required safeguards; the associates would need to provide a written analysis of relevant electronic information systems by a subject matter expert and a written certification that the analysis has been performed and is accurate. In the past, the rule “only required that you sign a business associate agreement” with the associate, which could be a payer, a pharmacy, or another physician practice, said Fox. The rule would require all entities to get certification that the controls are in place.
- Requiring a detailed map of an electronic network. For a physician practice, that means creating an inventory of all the technology assets, including devices, applications, and anything that would touch electronic PHI, and then creating a map of how it comes into the office, flows through it, and departs, said Greene.
- Having a plan of action in the case of a breach. The rule will require written procedures to restore certain relevant systems and data within 72 hours and written incident response plans.
Some physician practices — especially those still relying on passwords instead of more sophisticated MFA or encryption — may have to invest significantly to strengthen their information security, said Greene. Smaller organizations, for example, may need to upgrade systems to ensure that user access is terminated within an hour after someone’s employment ends.
Carr said practices should not view the investments as a burden. The regulation “will force practices to implement best cybersecurity practices,” she said.
Implementing those best practices serves as insurance, said Fox. He suggests that anyone in doubt “talk to someone who’s actually lived through a breach and had to recover.”
Tampa General Hospital in Florida, for instance, recently settled a class action suit, agreeing to pay $6.8 million to patients whose PHI was compromised.
It is not certain whether or when the health cybersecurity rule will be made final.
The incoming Trump administration could cancel or delay the rulemaking process.
Even if it continues, “I would not expect a final rule in 2025,” said Greene. He estimates that the rule would not take effect until at least 2026; healthcare entities would have 180 days to comply. Still, those 180 days can go by fast.
“I would say don’t panic, but don’t ignore it either,” he said.
A version of this article first appeared on Medscape.com.
A new federal rule could force hospitals and doctors’ groups to boost health cybersecurity measures to better protect patients’ health information and prevent ransomware attacks.
The proposed rule, issued by the US Department of Health & Human Services (HHS) and published on January 6 in the Federal Register, marks the first time in a decade that the federal government has updated regulations governing the security of private health information (PHI) that’s kept or shared online. Comments on the rule are due on March 6.
Because the risks for cyberattacks have increased exponentially, “there is a greater need to invest than ever before in both people and technologies to secure patient information,” Adam Greene, an attorney at Davis Wright Tremaine in Washington, DC, who advises healthcare clients on cybersecurity, said in an interview.
Bad actors continue to evolve and are often far ahead of their targets, added Mark Fox, privacy and research compliance officer for the American College of Cardiology.
In the proposed rule, HHS noted that breaches have risen by more than 50% since 2020. Damages from health data breaches are more expensive than in any other sector, averaging $10 million per incident, said HHS.
The damage can continue for years, as much of the data — such as date of birth — in PHI are “immutable,” unlike a credit card number, the agency said. A review of breach reports made to HHS’ Office for Civil Rights shows near-daily data breaches affecting hundreds to tens of thousands of patients. Since December 1 alone, healthcare providers reported breaches affecting nearly 3 million US patients, according to federal data.
Debi Carr, a Florida-based cybersecurity consultant for small physician and dental practices, welcomed the new proposal. “Many practices are clinging to doing things the way they have always done it, and hackers are taking full advantage of that mindset,” she said in an interview. “We have to change our mindset.”
Among the proposal’s recommendations:
- A shift away from making security specifications “addressable” to required. Fox said that many interpreted addressable to mean optional. The clarification is important. The government will require greater accountability, including a requirement to annually revise the risk analysis, to review policies and procedures and implementation, and to perform penetration testing, said Greene.
- Requiring multifactor authentication (MFA) and encryption of PHI at rest and in transit. “A reasonable person who does security will tell you that should be a requirement,” said Fox. Carr added that the February 2024 Change Healthcare ransomware attack happened because workers at the payment processing company were not using MFA.
- Requiring all entities to verify at least once a year that “business associates” have put into place the required safeguards; the associates would need to provide a written analysis of relevant electronic information systems by a subject matter expert and a written certification that the analysis has been performed and is accurate. In the past, the rule “only required that you sign a business associate agreement” with the associate, which could be a payer, a pharmacy, or another physician practice, said Fox. The rule would require all entities to get certification that the controls are in place.
- Requiring a detailed map of an electronic network. For a physician practice, that means creating an inventory of all the technology assets, including devices, applications, and anything that would touch electronic PHI, and then creating a map of how it comes into the office, flows through it, and departs, said Greene.
- Having a plan of action in the case of a breach. The rule will require written procedures to restore certain relevant systems and data within 72 hours and written incident response plans.
Some physician practices — especially those still relying on passwords instead of more sophisticated MFA or encryption — may have to invest significantly to strengthen their information security, said Greene. Smaller organizations, for example, may need to upgrade systems to ensure that user access is terminated within an hour after someone’s employment ends.
Carr said practices should not view the investments as a burden. The regulation “will force practices to implement best cybersecurity practices,” she said.
Implementing those best practices serves as insurance, said Fox. He suggests that anyone in doubt “talk to someone who’s actually lived through a breach and had to recover.”
Tampa General Hospital in Florida, for instance, recently settled a class action suit, agreeing to pay $6.8 million to patients whose PHI was compromised.
It is not certain whether or when the health cybersecurity rule will be made final.
The incoming Trump administration could cancel or delay the rulemaking process.
Even if it continues, “I would not expect a final rule in 2025,” said Greene. He estimates that the rule would not take effect until at least 2026; healthcare entities would have 180 days to comply. Still, those 180 days can go by fast.
“I would say don’t panic, but don’t ignore it either,” he said.
A version of this article first appeared on Medscape.com.
Retatrutide Produces Greatest Weight Loss
A systematic review of 26 randomized controlled trials (RCTs) finds that, among glucagon-like peptide 1 (GLP-1) receptor agonists and co-agonists on the market or still being investigated, the experimental drug retatrutide (Eli Lilly) produces the greatest weight loss.
The review, conducted by researchers at McGill University, Montreal, Quebec, Canada, examined three commercially available medications in the class and nine that have not yet received regulatory approval.
In healthy adults with overweight or obesity who did not have diabetes, the highest mean reductions in relative and absolute body weight were achieved with once-weekly triple glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 and glucagon receptor agonist retatrutide, followed by the dual GIP/GLP-1 agonist tirzepatide (Eli Lilly) and lastly by the GLP-1 agonist semaglutide (Novo Nordisk), according to the authors.
The use of all the GLP-1s or co-agonist medications “led to decreased body mass index (BMI), waist circumference, SBP (systolic blood pressure), and DBP (diastolic blood pressure),” wrote the authors in Annals of Internal Medicine. All the medications had a similar safety profile.
The researchers did not find any head-to-head studies, so instead examined the results from 26 RCTs that enrolled more than 15,000 patients. Only trials with a treatment duration of at least 16 weeks were included, to ensure that patients had at least a month of a fixed dose.
Not surprisingly, the review found that, except for semaglutide, trials with “dual and triple agonists generally reported numerically greater mean weight losses than single GLP-1 agonists.”
They caution, however, against drawing conclusions about comparative efficacy, as the populations, control groups, and contexts of the various studies might not be directly comparable. All the trial enrollees also received lifestyle modification along with drug therapy or placebo, but the interventions and protocols varied across the studies.
The authors found that individuals on retatrutide (12-mg once-weekly injection) lost 22% of body weight from baseline after 48 weeks. Tirzepatide (15 mg once-weekly injection) recipients lost almost 18% of body weight after 72 weeks, while those on semaglutide (2.4-mg once-weekly injection) lost about 14% after 68 weeks. Both tirzepatide and semaglutide are commercially available.
Patients taking liraglutide (3-mg once-daily injection), also on the market, lost up to 6% of body weight after 26 weeks.
The authors also examined studies of investigational agents and reported that the greatest loss, aside from retatrutide, was with the dual glucagon/GLP-1 agonists survodutide (Boehringer Ingelheim; 6%-15%) and mazdutide (Innovent Biologics; 7%-11%).
Orforglipron (Eli Lilly), a once-daily pill, produced weight loss of 9%-15%, depending on the dose.
The study found that four investigational drugs did not produce as much weight loss: Beinaglutide (0.2-mg injection three times daily, 6%), efpeglenatide (4- to 8-mg injection once weekly, about 7%), exenatide (10-mcg injection twice daily, 5-kg change in weight), and noiiglutide (once-daily injection, 9%).
The most common adverse events for all GLP-1s were gastrointestinal (GI), such as nausea, diarrhea, constipation, and vomiting. Across all agents, 60%-80% of patients taking the medications experienced a GI adverse event, although most were transient, according to the authors. A total of 6%-26% of patients discontinued treatment as a result of a side effect.
The authors said that no serious GI disorders, such as bowel obstruction or gastroparesis, were reported in any of the 26 trials.
The review also shows that it is likely that GLP-1s would have to be used chronically to have the greatest effect, said the authors. They noted that they found that trials “with longer treatment durations demonstrate similar weight loss results to those with shorter follow-up, reinforcing the idea that continuous treatment may be required.”
One coauthor reported receiving payments or honoraria from Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, and Novo Nordisk. The study was carried out independently without any grant or other funding.
A version of this article first appeared on Medscape.com.
A systematic review of 26 randomized controlled trials (RCTs) finds that, among glucagon-like peptide 1 (GLP-1) receptor agonists and co-agonists on the market or still being investigated, the experimental drug retatrutide (Eli Lilly) produces the greatest weight loss.
The review, conducted by researchers at McGill University, Montreal, Quebec, Canada, examined three commercially available medications in the class and nine that have not yet received regulatory approval.
In healthy adults with overweight or obesity who did not have diabetes, the highest mean reductions in relative and absolute body weight were achieved with once-weekly triple glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 and glucagon receptor agonist retatrutide, followed by the dual GIP/GLP-1 agonist tirzepatide (Eli Lilly) and lastly by the GLP-1 agonist semaglutide (Novo Nordisk), according to the authors.
The use of all the GLP-1s or co-agonist medications “led to decreased body mass index (BMI), waist circumference, SBP (systolic blood pressure), and DBP (diastolic blood pressure),” wrote the authors in Annals of Internal Medicine. All the medications had a similar safety profile.
The researchers did not find any head-to-head studies, so instead examined the results from 26 RCTs that enrolled more than 15,000 patients. Only trials with a treatment duration of at least 16 weeks were included, to ensure that patients had at least a month of a fixed dose.
Not surprisingly, the review found that, except for semaglutide, trials with “dual and triple agonists generally reported numerically greater mean weight losses than single GLP-1 agonists.”
They caution, however, against drawing conclusions about comparative efficacy, as the populations, control groups, and contexts of the various studies might not be directly comparable. All the trial enrollees also received lifestyle modification along with drug therapy or placebo, but the interventions and protocols varied across the studies.
The authors found that individuals on retatrutide (12-mg once-weekly injection) lost 22% of body weight from baseline after 48 weeks. Tirzepatide (15 mg once-weekly injection) recipients lost almost 18% of body weight after 72 weeks, while those on semaglutide (2.4-mg once-weekly injection) lost about 14% after 68 weeks. Both tirzepatide and semaglutide are commercially available.
Patients taking liraglutide (3-mg once-daily injection), also on the market, lost up to 6% of body weight after 26 weeks.
The authors also examined studies of investigational agents and reported that the greatest loss, aside from retatrutide, was with the dual glucagon/GLP-1 agonists survodutide (Boehringer Ingelheim; 6%-15%) and mazdutide (Innovent Biologics; 7%-11%).
Orforglipron (Eli Lilly), a once-daily pill, produced weight loss of 9%-15%, depending on the dose.
The study found that four investigational drugs did not produce as much weight loss: Beinaglutide (0.2-mg injection three times daily, 6%), efpeglenatide (4- to 8-mg injection once weekly, about 7%), exenatide (10-mcg injection twice daily, 5-kg change in weight), and noiiglutide (once-daily injection, 9%).
The most common adverse events for all GLP-1s were gastrointestinal (GI), such as nausea, diarrhea, constipation, and vomiting. Across all agents, 60%-80% of patients taking the medications experienced a GI adverse event, although most were transient, according to the authors. A total of 6%-26% of patients discontinued treatment as a result of a side effect.
The authors said that no serious GI disorders, such as bowel obstruction or gastroparesis, were reported in any of the 26 trials.
The review also shows that it is likely that GLP-1s would have to be used chronically to have the greatest effect, said the authors. They noted that they found that trials “with longer treatment durations demonstrate similar weight loss results to those with shorter follow-up, reinforcing the idea that continuous treatment may be required.”
One coauthor reported receiving payments or honoraria from Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, and Novo Nordisk. The study was carried out independently without any grant or other funding.
A version of this article first appeared on Medscape.com.
A systematic review of 26 randomized controlled trials (RCTs) finds that, among glucagon-like peptide 1 (GLP-1) receptor agonists and co-agonists on the market or still being investigated, the experimental drug retatrutide (Eli Lilly) produces the greatest weight loss.
The review, conducted by researchers at McGill University, Montreal, Quebec, Canada, examined three commercially available medications in the class and nine that have not yet received regulatory approval.
In healthy adults with overweight or obesity who did not have diabetes, the highest mean reductions in relative and absolute body weight were achieved with once-weekly triple glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 and glucagon receptor agonist retatrutide, followed by the dual GIP/GLP-1 agonist tirzepatide (Eli Lilly) and lastly by the GLP-1 agonist semaglutide (Novo Nordisk), according to the authors.
The use of all the GLP-1s or co-agonist medications “led to decreased body mass index (BMI), waist circumference, SBP (systolic blood pressure), and DBP (diastolic blood pressure),” wrote the authors in Annals of Internal Medicine. All the medications had a similar safety profile.
The researchers did not find any head-to-head studies, so instead examined the results from 26 RCTs that enrolled more than 15,000 patients. Only trials with a treatment duration of at least 16 weeks were included, to ensure that patients had at least a month of a fixed dose.
Not surprisingly, the review found that, except for semaglutide, trials with “dual and triple agonists generally reported numerically greater mean weight losses than single GLP-1 agonists.”
They caution, however, against drawing conclusions about comparative efficacy, as the populations, control groups, and contexts of the various studies might not be directly comparable. All the trial enrollees also received lifestyle modification along with drug therapy or placebo, but the interventions and protocols varied across the studies.
The authors found that individuals on retatrutide (12-mg once-weekly injection) lost 22% of body weight from baseline after 48 weeks. Tirzepatide (15 mg once-weekly injection) recipients lost almost 18% of body weight after 72 weeks, while those on semaglutide (2.4-mg once-weekly injection) lost about 14% after 68 weeks. Both tirzepatide and semaglutide are commercially available.
Patients taking liraglutide (3-mg once-daily injection), also on the market, lost up to 6% of body weight after 26 weeks.
The authors also examined studies of investigational agents and reported that the greatest loss, aside from retatrutide, was with the dual glucagon/GLP-1 agonists survodutide (Boehringer Ingelheim; 6%-15%) and mazdutide (Innovent Biologics; 7%-11%).
Orforglipron (Eli Lilly), a once-daily pill, produced weight loss of 9%-15%, depending on the dose.
The study found that four investigational drugs did not produce as much weight loss: Beinaglutide (0.2-mg injection three times daily, 6%), efpeglenatide (4- to 8-mg injection once weekly, about 7%), exenatide (10-mcg injection twice daily, 5-kg change in weight), and noiiglutide (once-daily injection, 9%).
The most common adverse events for all GLP-1s were gastrointestinal (GI), such as nausea, diarrhea, constipation, and vomiting. Across all agents, 60%-80% of patients taking the medications experienced a GI adverse event, although most were transient, according to the authors. A total of 6%-26% of patients discontinued treatment as a result of a side effect.
The authors said that no serious GI disorders, such as bowel obstruction or gastroparesis, were reported in any of the 26 trials.
The review also shows that it is likely that GLP-1s would have to be used chronically to have the greatest effect, said the authors. They noted that they found that trials “with longer treatment durations demonstrate similar weight loss results to those with shorter follow-up, reinforcing the idea that continuous treatment may be required.”
One coauthor reported receiving payments or honoraria from Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, and Novo Nordisk. The study was carried out independently without any grant or other funding.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
The Evidence Gap: Immunotherapy Timing in Early-Stage NSCLC?
Since October 2023, the US Food and Drug Administration (FDA) has approved three checkpoint inhibitors — pembrolizumab (Keytruda), durvalumab (Imfinzi), and most recently nivolumab (Opdivo) — alongside platinum-containing chemotherapy before surgery and as monotherapy after surgery to treat resectable NSCLC.
But the trials leading to each approval had a major design flaw. The studies failed to distinguish when patients with resectable NSCLC benefited from immunotherapy — before surgery, after surgery, or at both points.
That missing piece has left oncologists without definitive guidance on how best to treat their patients with resectable disease.
Jamie E. Chaft, MD, a thoracic medical oncologist and attending physician at Memorial Sloan Kettering Cancer Center in New York City, was “surprised” that the FDA had approved the three immunotherapy combination regimens without this clarity. Clinicians are now left with studies that can’t evaluate the contribution of the neoadjuvant and adjuvant phases, she said.
But that may soon change.
In July, an FDA advisory committee met to discuss the pending approval of durvalumab.
During this July meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) called out issues with AstraZeneca’s design of the trial, expressing concern that AstraZeneca had not followed the agency’s advice to compare patient outcomes with durvalumab in the neoadjuvant and adjuvant phases.
The ODAC panel ultimately voted unanimously in favor of requiring drug companies to demonstrate that patients need immunotherapy both before and after surgery in resectable NSCLC. Several panelists said this requirement should extend beyond NSCLC to other tumor types.
“We need to understand who needs what therapy when,” Daniel Spratt, MD, chairman of the FDA’s ODAC, told Medscape Medical News.
But even if the FDA does require drug companies to assess the benefit of immunotherapy pre- and post-surgery, will oncologists get the answers they need for their patients with resectable NSCLC? Or will the new costly trial design requirements dead-end progress in this space?
Treating Patients Without Clear Evidence
Despite the ODAC’s strong urging to require — not simply request — that drug companies show patients with resectable NSCLC benefit from immunotherapy in both the neoadjuvant and adjuvant settings, the advisory panel did not think durvalumab’s approval should be delayed until the neoadjuvant vs adjuvant question is answered.
A month later, in August, the FDA approved durvalumab for this indication.
Pembrolizumab (Keytruda, Merck) had already been approved 10 months earlier in the neoadjuvant and adjuvant settings in this setting. And most recently, in October, the FDA added nivolumab (Opdivo, Bristol Myers Squibb) to these approvals.
No trial, however, identified when patients benefited from the drug.
Without this understanding, patients may be taking immunotherapy unnecessarily, at significant expense and toxicity risk.
“Toxicities from immunotherapy can occur at any time after initiation,” said Joshua Eric Reuss, MD, a thoracic medical oncologist at Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, DC. And these “risks definitely continue into the adjuvant period.”
So far, the available evidence does suggest that the neoadjuvant phase of immunotherapy confers the greatest benefit, while adjuvant immunotherapy — which can last a year or longer — may expose patients to more costs and toxicities, with no clear benefit.
A 2024 meta-analysis, which included four trials of neoadjuvant-adjuvant immunotherapy and one trial of neoadjuvant immunotherapy in resectable NSCLC, suggested that the addition of adjuvant immunotherapy did not improve event-free survival (hazard ratio [HR], 0.90; P = .59) or overall survival (HR, 1.18; P = .51) compared with neoadjuvant immunotherapy alone.
According to Spratt, “It’s very clear that the neoadjuvant phase is the more important of the two phases.” Given that, “we’re probably overtreating some patients,” said Spratt, also chairman of Radiation Oncology at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland.
Chaft agreed that “there’s very little data that we need the postoperative phase, and what data we do have is post hoc and limited.”
This evidence gap “has created considerable dilemmas” for oncologists and patients who are faced with “the challenge of deciding which therapeutic options or approach are best suited for each individual,” experts wrote in recent consensus recommendations from the International Association for the Study of Lung Cancer.
Clinicians may ultimately be left to make decisions about prescribing postoperative immunotherapy based on their experience and comfort level.
When Chaft’s patients have a pathologic complete response with immunotherapy and chemotherapy in the neoadjuvant phase, “I’m comfortable stopping because the data would suggest they’re almost certainly cured,” she said.
For patients who have viable disease after neoadjuvant therapy, continuing an immunotherapy postoperatively when it didn’t work preoperatively “is not going to make a difference,” Chaft explained. In these cases, Chaft would look to enroll them in a clinical trial evaluating a different regimen because of the risk for relapse.
With patients who did well preoperatively but still have tumor left at the time of surgery, she would discuss continuing the immunotherapy or participating in a trial, she said.
All the FDA-approved regimens are covered by insurance, said Chaft. Clinicians are most comfortable with pembrolizumab because it is the most widely used immunotherapy in advanced NSCLC, she said. But, she added, “there’s really no strong differentiating data between any of the studies; all the results look very comparable.”
When assessing whether a patient may benefit from immunotherapy after surgery, Reuss looks at a range of factors, including disease stage, histology, gene mutations, and pathologic response. Reuss also weighs patient preferences. A patient coming from another country might only want a neoadjuvant regimen, for instance, he said.
That “isn’t exactly the kind of the level one evidence that one likes to see when making treatment decisions,” said Reuss. “Without prospective data, all we can do is cross-trial comparisons and assessment of subgroups.”
If a new regimen comes along that improves outcomes or decision-making, “I think we would pivot to that in a heartbeat,” he said.
But Will FDA Follow ODAC’s Recommendation?
“ODAC has made their point clear,” said Chaft. “Our patients deserve to know that whatever added risk and cost they’re incurring is merited by a clinical outcome.”
Despite the ODAC’s recommendation, it’s not guaranteed that the FDA will follow it.
An FDA spokesperson did not confirm the agency’s decision on the matter but noted that the FDA is “incorporating the panel’s advice.”
Spratt thinks that, going forward, companies will be held to “a higher bar,” but it’s unclear what that bar will look like.
“Whether this is a mandate or a strong recommendation, I think industry is definitely paying attention,” Spratt said. Companies that do not follow the guidance may risk not having their drug approved, “unless it’s just an absolute huge slam dunk of a major benefit to patients.”
In fact, according to Chaft, drug makers seeking approvals of novel entities in this space “won’t have a choice” but to follow any new trial design requirements from the FDA.
Still, getting answers may be a challenge.
Drug companies with immunotherapies already on the market are unlikely to invest the resources to conduct trials comparing the neoadjuvant and adjuvant settings, said Chaft. “It will take too long and cost too much,” she said.
And it remains unclear whether drug companies will decide to stop pursuing novel agents if approvals will ultimately require more expensive and time-consuming trials.
According to Chaft, oncologists have been discussing protocols that could help fill the knowledge gaps. Such trials will be conducted by the National Cancer Institute’s Cooperative Groups, she noted. But it’s early days.
For the time being, with comparative data from phase 3 trials years away, oncologists will have to work with the limited evidence and individual patients in front of them.
Chaft disclosed ties with AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Genentech/Roche, Guardant Health, Janssen Pharmaceuticals, Eli Lilly, and Merck. Reuss disclosed ties with AstraZeneca, Arcus, AbbVie, Bristol Myers Squibb, CatalYm, Daiichi Sankyo, and Eli Lilly, and that Georgetown has received research funding from Genentech/Roche, Verastem, Nuvalent, LUNGevity Foundation, Exelixis, Arcus, and Revolution Medicines. Spratt disclosed ties with Astellas, AstraZeneca, Bayer, Boston Scientific, Janssen Pharmaceuticals, Novartis, and Pfizer.
A version of this article appeared on Medscape.com.
Since October 2023, the US Food and Drug Administration (FDA) has approved three checkpoint inhibitors — pembrolizumab (Keytruda), durvalumab (Imfinzi), and most recently nivolumab (Opdivo) — alongside platinum-containing chemotherapy before surgery and as monotherapy after surgery to treat resectable NSCLC.
But the trials leading to each approval had a major design flaw. The studies failed to distinguish when patients with resectable NSCLC benefited from immunotherapy — before surgery, after surgery, or at both points.
That missing piece has left oncologists without definitive guidance on how best to treat their patients with resectable disease.
Jamie E. Chaft, MD, a thoracic medical oncologist and attending physician at Memorial Sloan Kettering Cancer Center in New York City, was “surprised” that the FDA had approved the three immunotherapy combination regimens without this clarity. Clinicians are now left with studies that can’t evaluate the contribution of the neoadjuvant and adjuvant phases, she said.
But that may soon change.
In July, an FDA advisory committee met to discuss the pending approval of durvalumab.
During this July meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) called out issues with AstraZeneca’s design of the trial, expressing concern that AstraZeneca had not followed the agency’s advice to compare patient outcomes with durvalumab in the neoadjuvant and adjuvant phases.
The ODAC panel ultimately voted unanimously in favor of requiring drug companies to demonstrate that patients need immunotherapy both before and after surgery in resectable NSCLC. Several panelists said this requirement should extend beyond NSCLC to other tumor types.
“We need to understand who needs what therapy when,” Daniel Spratt, MD, chairman of the FDA’s ODAC, told Medscape Medical News.
But even if the FDA does require drug companies to assess the benefit of immunotherapy pre- and post-surgery, will oncologists get the answers they need for their patients with resectable NSCLC? Or will the new costly trial design requirements dead-end progress in this space?
Treating Patients Without Clear Evidence
Despite the ODAC’s strong urging to require — not simply request — that drug companies show patients with resectable NSCLC benefit from immunotherapy in both the neoadjuvant and adjuvant settings, the advisory panel did not think durvalumab’s approval should be delayed until the neoadjuvant vs adjuvant question is answered.
A month later, in August, the FDA approved durvalumab for this indication.
Pembrolizumab (Keytruda, Merck) had already been approved 10 months earlier in the neoadjuvant and adjuvant settings in this setting. And most recently, in October, the FDA added nivolumab (Opdivo, Bristol Myers Squibb) to these approvals.
No trial, however, identified when patients benefited from the drug.
Without this understanding, patients may be taking immunotherapy unnecessarily, at significant expense and toxicity risk.
“Toxicities from immunotherapy can occur at any time after initiation,” said Joshua Eric Reuss, MD, a thoracic medical oncologist at Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, DC. And these “risks definitely continue into the adjuvant period.”
So far, the available evidence does suggest that the neoadjuvant phase of immunotherapy confers the greatest benefit, while adjuvant immunotherapy — which can last a year or longer — may expose patients to more costs and toxicities, with no clear benefit.
A 2024 meta-analysis, which included four trials of neoadjuvant-adjuvant immunotherapy and one trial of neoadjuvant immunotherapy in resectable NSCLC, suggested that the addition of adjuvant immunotherapy did not improve event-free survival (hazard ratio [HR], 0.90; P = .59) or overall survival (HR, 1.18; P = .51) compared with neoadjuvant immunotherapy alone.
According to Spratt, “It’s very clear that the neoadjuvant phase is the more important of the two phases.” Given that, “we’re probably overtreating some patients,” said Spratt, also chairman of Radiation Oncology at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland.
Chaft agreed that “there’s very little data that we need the postoperative phase, and what data we do have is post hoc and limited.”
This evidence gap “has created considerable dilemmas” for oncologists and patients who are faced with “the challenge of deciding which therapeutic options or approach are best suited for each individual,” experts wrote in recent consensus recommendations from the International Association for the Study of Lung Cancer.
Clinicians may ultimately be left to make decisions about prescribing postoperative immunotherapy based on their experience and comfort level.
When Chaft’s patients have a pathologic complete response with immunotherapy and chemotherapy in the neoadjuvant phase, “I’m comfortable stopping because the data would suggest they’re almost certainly cured,” she said.
For patients who have viable disease after neoadjuvant therapy, continuing an immunotherapy postoperatively when it didn’t work preoperatively “is not going to make a difference,” Chaft explained. In these cases, Chaft would look to enroll them in a clinical trial evaluating a different regimen because of the risk for relapse.
With patients who did well preoperatively but still have tumor left at the time of surgery, she would discuss continuing the immunotherapy or participating in a trial, she said.
All the FDA-approved regimens are covered by insurance, said Chaft. Clinicians are most comfortable with pembrolizumab because it is the most widely used immunotherapy in advanced NSCLC, she said. But, she added, “there’s really no strong differentiating data between any of the studies; all the results look very comparable.”
When assessing whether a patient may benefit from immunotherapy after surgery, Reuss looks at a range of factors, including disease stage, histology, gene mutations, and pathologic response. Reuss also weighs patient preferences. A patient coming from another country might only want a neoadjuvant regimen, for instance, he said.
That “isn’t exactly the kind of the level one evidence that one likes to see when making treatment decisions,” said Reuss. “Without prospective data, all we can do is cross-trial comparisons and assessment of subgroups.”
If a new regimen comes along that improves outcomes or decision-making, “I think we would pivot to that in a heartbeat,” he said.
But Will FDA Follow ODAC’s Recommendation?
“ODAC has made their point clear,” said Chaft. “Our patients deserve to know that whatever added risk and cost they’re incurring is merited by a clinical outcome.”
Despite the ODAC’s recommendation, it’s not guaranteed that the FDA will follow it.
An FDA spokesperson did not confirm the agency’s decision on the matter but noted that the FDA is “incorporating the panel’s advice.”
Spratt thinks that, going forward, companies will be held to “a higher bar,” but it’s unclear what that bar will look like.
“Whether this is a mandate or a strong recommendation, I think industry is definitely paying attention,” Spratt said. Companies that do not follow the guidance may risk not having their drug approved, “unless it’s just an absolute huge slam dunk of a major benefit to patients.”
In fact, according to Chaft, drug makers seeking approvals of novel entities in this space “won’t have a choice” but to follow any new trial design requirements from the FDA.
Still, getting answers may be a challenge.
Drug companies with immunotherapies already on the market are unlikely to invest the resources to conduct trials comparing the neoadjuvant and adjuvant settings, said Chaft. “It will take too long and cost too much,” she said.
And it remains unclear whether drug companies will decide to stop pursuing novel agents if approvals will ultimately require more expensive and time-consuming trials.
According to Chaft, oncologists have been discussing protocols that could help fill the knowledge gaps. Such trials will be conducted by the National Cancer Institute’s Cooperative Groups, she noted. But it’s early days.
For the time being, with comparative data from phase 3 trials years away, oncologists will have to work with the limited evidence and individual patients in front of them.
Chaft disclosed ties with AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Genentech/Roche, Guardant Health, Janssen Pharmaceuticals, Eli Lilly, and Merck. Reuss disclosed ties with AstraZeneca, Arcus, AbbVie, Bristol Myers Squibb, CatalYm, Daiichi Sankyo, and Eli Lilly, and that Georgetown has received research funding from Genentech/Roche, Verastem, Nuvalent, LUNGevity Foundation, Exelixis, Arcus, and Revolution Medicines. Spratt disclosed ties with Astellas, AstraZeneca, Bayer, Boston Scientific, Janssen Pharmaceuticals, Novartis, and Pfizer.
A version of this article appeared on Medscape.com.
Since October 2023, the US Food and Drug Administration (FDA) has approved three checkpoint inhibitors — pembrolizumab (Keytruda), durvalumab (Imfinzi), and most recently nivolumab (Opdivo) — alongside platinum-containing chemotherapy before surgery and as monotherapy after surgery to treat resectable NSCLC.
But the trials leading to each approval had a major design flaw. The studies failed to distinguish when patients with resectable NSCLC benefited from immunotherapy — before surgery, after surgery, or at both points.
That missing piece has left oncologists without definitive guidance on how best to treat their patients with resectable disease.
Jamie E. Chaft, MD, a thoracic medical oncologist and attending physician at Memorial Sloan Kettering Cancer Center in New York City, was “surprised” that the FDA had approved the three immunotherapy combination regimens without this clarity. Clinicians are now left with studies that can’t evaluate the contribution of the neoadjuvant and adjuvant phases, she said.
But that may soon change.
In July, an FDA advisory committee met to discuss the pending approval of durvalumab.
During this July meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) called out issues with AstraZeneca’s design of the trial, expressing concern that AstraZeneca had not followed the agency’s advice to compare patient outcomes with durvalumab in the neoadjuvant and adjuvant phases.
The ODAC panel ultimately voted unanimously in favor of requiring drug companies to demonstrate that patients need immunotherapy both before and after surgery in resectable NSCLC. Several panelists said this requirement should extend beyond NSCLC to other tumor types.
“We need to understand who needs what therapy when,” Daniel Spratt, MD, chairman of the FDA’s ODAC, told Medscape Medical News.
But even if the FDA does require drug companies to assess the benefit of immunotherapy pre- and post-surgery, will oncologists get the answers they need for their patients with resectable NSCLC? Or will the new costly trial design requirements dead-end progress in this space?
Treating Patients Without Clear Evidence
Despite the ODAC’s strong urging to require — not simply request — that drug companies show patients with resectable NSCLC benefit from immunotherapy in both the neoadjuvant and adjuvant settings, the advisory panel did not think durvalumab’s approval should be delayed until the neoadjuvant vs adjuvant question is answered.
A month later, in August, the FDA approved durvalumab for this indication.
Pembrolizumab (Keytruda, Merck) had already been approved 10 months earlier in the neoadjuvant and adjuvant settings in this setting. And most recently, in October, the FDA added nivolumab (Opdivo, Bristol Myers Squibb) to these approvals.
No trial, however, identified when patients benefited from the drug.
Without this understanding, patients may be taking immunotherapy unnecessarily, at significant expense and toxicity risk.
“Toxicities from immunotherapy can occur at any time after initiation,” said Joshua Eric Reuss, MD, a thoracic medical oncologist at Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, DC. And these “risks definitely continue into the adjuvant period.”
So far, the available evidence does suggest that the neoadjuvant phase of immunotherapy confers the greatest benefit, while adjuvant immunotherapy — which can last a year or longer — may expose patients to more costs and toxicities, with no clear benefit.
A 2024 meta-analysis, which included four trials of neoadjuvant-adjuvant immunotherapy and one trial of neoadjuvant immunotherapy in resectable NSCLC, suggested that the addition of adjuvant immunotherapy did not improve event-free survival (hazard ratio [HR], 0.90; P = .59) or overall survival (HR, 1.18; P = .51) compared with neoadjuvant immunotherapy alone.
According to Spratt, “It’s very clear that the neoadjuvant phase is the more important of the two phases.” Given that, “we’re probably overtreating some patients,” said Spratt, also chairman of Radiation Oncology at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland.
Chaft agreed that “there’s very little data that we need the postoperative phase, and what data we do have is post hoc and limited.”
This evidence gap “has created considerable dilemmas” for oncologists and patients who are faced with “the challenge of deciding which therapeutic options or approach are best suited for each individual,” experts wrote in recent consensus recommendations from the International Association for the Study of Lung Cancer.
Clinicians may ultimately be left to make decisions about prescribing postoperative immunotherapy based on their experience and comfort level.
When Chaft’s patients have a pathologic complete response with immunotherapy and chemotherapy in the neoadjuvant phase, “I’m comfortable stopping because the data would suggest they’re almost certainly cured,” she said.
For patients who have viable disease after neoadjuvant therapy, continuing an immunotherapy postoperatively when it didn’t work preoperatively “is not going to make a difference,” Chaft explained. In these cases, Chaft would look to enroll them in a clinical trial evaluating a different regimen because of the risk for relapse.
With patients who did well preoperatively but still have tumor left at the time of surgery, she would discuss continuing the immunotherapy or participating in a trial, she said.
All the FDA-approved regimens are covered by insurance, said Chaft. Clinicians are most comfortable with pembrolizumab because it is the most widely used immunotherapy in advanced NSCLC, she said. But, she added, “there’s really no strong differentiating data between any of the studies; all the results look very comparable.”
When assessing whether a patient may benefit from immunotherapy after surgery, Reuss looks at a range of factors, including disease stage, histology, gene mutations, and pathologic response. Reuss also weighs patient preferences. A patient coming from another country might only want a neoadjuvant regimen, for instance, he said.
That “isn’t exactly the kind of the level one evidence that one likes to see when making treatment decisions,” said Reuss. “Without prospective data, all we can do is cross-trial comparisons and assessment of subgroups.”
If a new regimen comes along that improves outcomes or decision-making, “I think we would pivot to that in a heartbeat,” he said.
But Will FDA Follow ODAC’s Recommendation?
“ODAC has made their point clear,” said Chaft. “Our patients deserve to know that whatever added risk and cost they’re incurring is merited by a clinical outcome.”
Despite the ODAC’s recommendation, it’s not guaranteed that the FDA will follow it.
An FDA spokesperson did not confirm the agency’s decision on the matter but noted that the FDA is “incorporating the panel’s advice.”
Spratt thinks that, going forward, companies will be held to “a higher bar,” but it’s unclear what that bar will look like.
“Whether this is a mandate or a strong recommendation, I think industry is definitely paying attention,” Spratt said. Companies that do not follow the guidance may risk not having their drug approved, “unless it’s just an absolute huge slam dunk of a major benefit to patients.”
In fact, according to Chaft, drug makers seeking approvals of novel entities in this space “won’t have a choice” but to follow any new trial design requirements from the FDA.
Still, getting answers may be a challenge.
Drug companies with immunotherapies already on the market are unlikely to invest the resources to conduct trials comparing the neoadjuvant and adjuvant settings, said Chaft. “It will take too long and cost too much,” she said.
And it remains unclear whether drug companies will decide to stop pursuing novel agents if approvals will ultimately require more expensive and time-consuming trials.
According to Chaft, oncologists have been discussing protocols that could help fill the knowledge gaps. Such trials will be conducted by the National Cancer Institute’s Cooperative Groups, she noted. But it’s early days.
For the time being, with comparative data from phase 3 trials years away, oncologists will have to work with the limited evidence and individual patients in front of them.
Chaft disclosed ties with AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Genentech/Roche, Guardant Health, Janssen Pharmaceuticals, Eli Lilly, and Merck. Reuss disclosed ties with AstraZeneca, Arcus, AbbVie, Bristol Myers Squibb, CatalYm, Daiichi Sankyo, and Eli Lilly, and that Georgetown has received research funding from Genentech/Roche, Verastem, Nuvalent, LUNGevity Foundation, Exelixis, Arcus, and Revolution Medicines. Spratt disclosed ties with Astellas, AstraZeneca, Bayer, Boston Scientific, Janssen Pharmaceuticals, Novartis, and Pfizer.
A version of this article appeared on Medscape.com.
70% of US Counties Have No Endocrinologist, New Study Finds
according to a new analysis by GoodRx, a company that provides discount coupons for medications.
A total of 50 million people who live in the 2168 counties without a practicing endocrinologist are at a higher risk for poor health outcomes, according to the analysis.
The author reported that individuals who live in endocrinology “deserts” are 12% more likely to die from endocrine-related conditions and have higher rates of diabetes, obesity, and stroke than those who live in counties where there are endocrinologists.
GoodRx’s finely detailed maps show that endocrinologists are clustered on the coasts and around major cities. Many counties have just a single endocrinologist and no pediatric endocrinologists.
Endocrinologists are not flocking to areas with a high type 2 diabetes prevalence — such as southern states, many parts of Texas, and counties with high concentrations of Native Americans or Alaskan Natives.
The maps speak volumes about disparities. In Sabine Parish, Louisiana, which shares a border with east Texas, the adult diabetes prevalence is 14%. The age-adjusted diabetes death rate is 52.6 per 100,000, in a population of 16,936 adults. There are no endocrinologists in that parish and one in a bordering parish.
In the entire state of Alaska, there are a total of two adult endocrinologists — one in Anchorage County and one in Fairbanks County — and two pediatric endocrinologists, both in Anchorage.
Buffalo County, South Dakota, which has no endocrinologists and is dominated by the Crow Creek Reservation, has a diabetes prevalence of 16.6% and a diabetes death rate of 143.3 per 100,000.
Connecticut’s Hartford County, however, has 69 adult endocrinologists and 9 pediatric endocrinologists. The adult diabetes prevalence is 0%, and the death rate is 26.3 per 100,000, in a population of 896,854.
To come up with its maps, GoodRx used population estimates from the 2024 Centers for Disease Control and Prevention (CDC) Places dataset and calculated adult diabetes rates and age-adjusted diabetes-related death rates per 100,000 using the 2024 CDC Places and CDC Wonder datasets. Data on the number of practicing endocrinologists came from HealthLink Dimensions, a company that provides databases for marketing purposes.
Robert Lash, MD, chief medical officer for The Endocrine Society, said that the GoodRx data are not especially new. Endocrinology “deserts” have existed for a decade or more, Lash said.
The GoodRx analysis concluded that a lack of endocrinologists in the “desert” counties directly led to higher death rates in those areas. “This is much more an association that it is causation,” countered Lash, noting that the deserts tend to align with healthcare professional shortage areas.
GoodRx also acknowledged the overlap and said that it could mean less access to primary care. In turn, “many patients may not even receive a diagnosis for endocrine-related conditions, let alone the specialized care they need,” wrote the analyst. “Preventable conditions like diabetes spiral into severe complications.”
Lash said seeking out a primary care doctor is one option for those without access to an endocrinologist. Telemedicine has also helped expand access, said Lash, adding that endocrinologists have been among the more frequent users.
Even so, the shortage of endocrinologists is an ongoing problem, he said. Only about 5000-6000 endocrinologists are actively practicing, estimates The Endocrine Society.
Fewer medical school graduates are choosing endocrinology, in part because of the lack of compensation, said Lash.
The society has begun a push to interest more students. Starting in 2024, The Society awarded grants to 10 medical schools to start endocrinology interest groups. The Medical School Engagement Program also sponsors two students for a VIP-type experience at the annual scientific meeting.
The hope is to boost interest in fellowships, which come after 3 years of internal medicine residency. Currently, there are only about 11 applicants for every 10 fellowship spots, said Lash.
It may be a while before the society’s experiment bears fruit. Those entering medical school in 2024 would not be eligible for fellowship until 2031, noted Lash.
“We’re in this for the long haul,” he said. “We know that this problem is not going to get solved overnight.”
A version of this article appeared on Medscape.com.
according to a new analysis by GoodRx, a company that provides discount coupons for medications.
A total of 50 million people who live in the 2168 counties without a practicing endocrinologist are at a higher risk for poor health outcomes, according to the analysis.
The author reported that individuals who live in endocrinology “deserts” are 12% more likely to die from endocrine-related conditions and have higher rates of diabetes, obesity, and stroke than those who live in counties where there are endocrinologists.
GoodRx’s finely detailed maps show that endocrinologists are clustered on the coasts and around major cities. Many counties have just a single endocrinologist and no pediatric endocrinologists.
Endocrinologists are not flocking to areas with a high type 2 diabetes prevalence — such as southern states, many parts of Texas, and counties with high concentrations of Native Americans or Alaskan Natives.
The maps speak volumes about disparities. In Sabine Parish, Louisiana, which shares a border with east Texas, the adult diabetes prevalence is 14%. The age-adjusted diabetes death rate is 52.6 per 100,000, in a population of 16,936 adults. There are no endocrinologists in that parish and one in a bordering parish.
In the entire state of Alaska, there are a total of two adult endocrinologists — one in Anchorage County and one in Fairbanks County — and two pediatric endocrinologists, both in Anchorage.
Buffalo County, South Dakota, which has no endocrinologists and is dominated by the Crow Creek Reservation, has a diabetes prevalence of 16.6% and a diabetes death rate of 143.3 per 100,000.
Connecticut’s Hartford County, however, has 69 adult endocrinologists and 9 pediatric endocrinologists. The adult diabetes prevalence is 0%, and the death rate is 26.3 per 100,000, in a population of 896,854.
To come up with its maps, GoodRx used population estimates from the 2024 Centers for Disease Control and Prevention (CDC) Places dataset and calculated adult diabetes rates and age-adjusted diabetes-related death rates per 100,000 using the 2024 CDC Places and CDC Wonder datasets. Data on the number of practicing endocrinologists came from HealthLink Dimensions, a company that provides databases for marketing purposes.
Robert Lash, MD, chief medical officer for The Endocrine Society, said that the GoodRx data are not especially new. Endocrinology “deserts” have existed for a decade or more, Lash said.
The GoodRx analysis concluded that a lack of endocrinologists in the “desert” counties directly led to higher death rates in those areas. “This is much more an association that it is causation,” countered Lash, noting that the deserts tend to align with healthcare professional shortage areas.
GoodRx also acknowledged the overlap and said that it could mean less access to primary care. In turn, “many patients may not even receive a diagnosis for endocrine-related conditions, let alone the specialized care they need,” wrote the analyst. “Preventable conditions like diabetes spiral into severe complications.”
Lash said seeking out a primary care doctor is one option for those without access to an endocrinologist. Telemedicine has also helped expand access, said Lash, adding that endocrinologists have been among the more frequent users.
Even so, the shortage of endocrinologists is an ongoing problem, he said. Only about 5000-6000 endocrinologists are actively practicing, estimates The Endocrine Society.
Fewer medical school graduates are choosing endocrinology, in part because of the lack of compensation, said Lash.
The society has begun a push to interest more students. Starting in 2024, The Society awarded grants to 10 medical schools to start endocrinology interest groups. The Medical School Engagement Program also sponsors two students for a VIP-type experience at the annual scientific meeting.
The hope is to boost interest in fellowships, which come after 3 years of internal medicine residency. Currently, there are only about 11 applicants for every 10 fellowship spots, said Lash.
It may be a while before the society’s experiment bears fruit. Those entering medical school in 2024 would not be eligible for fellowship until 2031, noted Lash.
“We’re in this for the long haul,” he said. “We know that this problem is not going to get solved overnight.”
A version of this article appeared on Medscape.com.
according to a new analysis by GoodRx, a company that provides discount coupons for medications.
A total of 50 million people who live in the 2168 counties without a practicing endocrinologist are at a higher risk for poor health outcomes, according to the analysis.
The author reported that individuals who live in endocrinology “deserts” are 12% more likely to die from endocrine-related conditions and have higher rates of diabetes, obesity, and stroke than those who live in counties where there are endocrinologists.
GoodRx’s finely detailed maps show that endocrinologists are clustered on the coasts and around major cities. Many counties have just a single endocrinologist and no pediatric endocrinologists.
Endocrinologists are not flocking to areas with a high type 2 diabetes prevalence — such as southern states, many parts of Texas, and counties with high concentrations of Native Americans or Alaskan Natives.
The maps speak volumes about disparities. In Sabine Parish, Louisiana, which shares a border with east Texas, the adult diabetes prevalence is 14%. The age-adjusted diabetes death rate is 52.6 per 100,000, in a population of 16,936 adults. There are no endocrinologists in that parish and one in a bordering parish.
In the entire state of Alaska, there are a total of two adult endocrinologists — one in Anchorage County and one in Fairbanks County — and two pediatric endocrinologists, both in Anchorage.
Buffalo County, South Dakota, which has no endocrinologists and is dominated by the Crow Creek Reservation, has a diabetes prevalence of 16.6% and a diabetes death rate of 143.3 per 100,000.
Connecticut’s Hartford County, however, has 69 adult endocrinologists and 9 pediatric endocrinologists. The adult diabetes prevalence is 0%, and the death rate is 26.3 per 100,000, in a population of 896,854.
To come up with its maps, GoodRx used population estimates from the 2024 Centers for Disease Control and Prevention (CDC) Places dataset and calculated adult diabetes rates and age-adjusted diabetes-related death rates per 100,000 using the 2024 CDC Places and CDC Wonder datasets. Data on the number of practicing endocrinologists came from HealthLink Dimensions, a company that provides databases for marketing purposes.
Robert Lash, MD, chief medical officer for The Endocrine Society, said that the GoodRx data are not especially new. Endocrinology “deserts” have existed for a decade or more, Lash said.
The GoodRx analysis concluded that a lack of endocrinologists in the “desert” counties directly led to higher death rates in those areas. “This is much more an association that it is causation,” countered Lash, noting that the deserts tend to align with healthcare professional shortage areas.
GoodRx also acknowledged the overlap and said that it could mean less access to primary care. In turn, “many patients may not even receive a diagnosis for endocrine-related conditions, let alone the specialized care they need,” wrote the analyst. “Preventable conditions like diabetes spiral into severe complications.”
Lash said seeking out a primary care doctor is one option for those without access to an endocrinologist. Telemedicine has also helped expand access, said Lash, adding that endocrinologists have been among the more frequent users.
Even so, the shortage of endocrinologists is an ongoing problem, he said. Only about 5000-6000 endocrinologists are actively practicing, estimates The Endocrine Society.
Fewer medical school graduates are choosing endocrinology, in part because of the lack of compensation, said Lash.
The society has begun a push to interest more students. Starting in 2024, The Society awarded grants to 10 medical schools to start endocrinology interest groups. The Medical School Engagement Program also sponsors two students for a VIP-type experience at the annual scientific meeting.
The hope is to boost interest in fellowships, which come after 3 years of internal medicine residency. Currently, there are only about 11 applicants for every 10 fellowship spots, said Lash.
It may be a while before the society’s experiment bears fruit. Those entering medical school in 2024 would not be eligible for fellowship until 2031, noted Lash.
“We’re in this for the long haul,” he said. “We know that this problem is not going to get solved overnight.”
A version of this article appeared on Medscape.com.
Should the FDA Reconsider Boxed Warnings for Antidepressants?
Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.
With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.
The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.
“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.
While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.
“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”
Decline in Diagnoses
The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.
Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.
In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.
Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.
He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.
Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.
“It makes sense based on the data that we have at hand now,” said Sakolsky.
The Dangers of Untreated Depression
Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.
“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.
Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.
Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.
In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.
Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.
Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.
The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.
The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.
“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”
Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.”
Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.
For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.
“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”
‘What Do We Do Now?’
When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.
The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.
Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”
The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.
But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.
While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.
“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”
The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.
What’s Next?
When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”
Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.
For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.
Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.”
After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”
Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.
Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.
A version of this article first appeared on Medscape.com.
Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.
With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.
The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.
“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.
While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.
“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”
Decline in Diagnoses
The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.
Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.
In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.
Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.
He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.
Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.
“It makes sense based on the data that we have at hand now,” said Sakolsky.
The Dangers of Untreated Depression
Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.
“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.
Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.
Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.
In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.
Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.
Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.
The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.
The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.
“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”
Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.”
Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.
For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.
“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”
‘What Do We Do Now?’
When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.
The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.
Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”
The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.
But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.
While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.
“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”
The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.
What’s Next?
When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”
Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.
For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.
Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.”
After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”
Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.
Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.
A version of this article first appeared on Medscape.com.
Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.
With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.
The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.
“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.
While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.
“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”
Decline in Diagnoses
The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.
Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.
In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.
Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.
He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.
Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.
“It makes sense based on the data that we have at hand now,” said Sakolsky.
The Dangers of Untreated Depression
Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.
“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.
Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.
Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.
In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.
Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.
Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.
The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.
The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.
“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”
Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.”
Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.
For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.
“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”
‘What Do We Do Now?’
When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.
The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.
Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”
The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.
But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.
While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.
“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”
The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.
What’s Next?
When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”
Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.
For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.
Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.”
After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”
Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.
Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.
A version of this article first appeared on Medscape.com.