Federal Practitioner

What if cardiology were no longer an internal medicine subspecialty? Four leading cardiology societies have announced plans to create a new certification process that is independent of the American Board of Internal Medicine maintenance of certification (MOC) system.

As envisioned, the new “independent, self-governed” entity would supplant the ABIM’s long-standing and widely criticized MOC system and establish cardiology as its own specialty with its own subspecialties. Long in coming, it is only the latest response to many in the field who for years have charged that the MOC system is needlessly burdensome and expensive.

“It’s time to have a dedicated cardiovascular medicine board of our own,” said B. Hadley Wilson, MD, in the group’s announcement. “Cardiology is a distinct medical specialty, and physicians want and deserve a clinical competency and continuous certification program that is meaningful to their practice and patients.”

Hadley Wilson, Sanger Heart & Vascular Institute Vascular Kenilworth, Charlotte, N.C., is president of the American College of Cardiology, one of the four societies spearheading the initiative along with the Heart Failure Society of America, the Heart Rhythm Society, and the Society for Cardiovascular Angiography & Interventions.

Their Sept. 21 statement says that the consortium will apply to the American Board of Medical Specialties to request an independent cardiology board that follows a “new competency-based approach to continuous certification – one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

It continues, “The new board requirements will de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills.”

“The new board’s focus on competence in the pursuit of continuous certification is a needed paradigm shift for the field,” states HFSA President John R. Teerlink, MD, University of California, San Francisco, and the San Francisco VA Medical Center, in the announcement.

“I commend these professional cardiovascular societies for taking on this important challenge,” Deepak L. Bhatt, MD, MPH, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York City, told this news organization by email.

“This is an incredible opportunity to redefine what ongoing cardiovascular education means to the contemporary practicing cardiologist in a way that is relevant to improving the care of actual patients,” said Dr. Bhatt, who chairs the ACC Accreditation Oversight Committee.

“There needs to be an agile, personalized, convenient, and effective system to assist practitioners to stay current with new knowledge and demonstrate the necessary competencies,” Harlan Krumholz, MD, said in an email.

“There is a deep sense in the profession that the current approaches do not meet the needs of clinicians or society,” said Dr. Krumholz, Yale School of Medicine, New Haven, Conn., who has sat on the ABIM board of directors.

“This effort, which now will create competition, has the potential to spark innovation,” he said. “The key is that any approach needs to ask the question, ‘Is the cost and effort producing benefit for patients and society?’ If it is not, we have not found the right system.”

In a statement in response to the new development, ABIM said it plans to continue “offering and administering” its existing MOC programs across all specialties.

“Any physician choosing to maintain their ABIM certification in these disciplines will continue to have a pathway with ABIM to do so,” it says. “Questions about the cardiovascular organizations’ announcement and how it may affect individual physicians are best answered by those organizations.”

The process of approving the heart societies’ application to ABMS “is expected to take several months,” their announcement states. If approval is granted, “it will then take several additional months before initial certification and continuous certification and competency programs would begin.”

Medscape provides educational content including MOC. Medscape’s editorial content, including news and features, is developed independently of the educational content available on Medscape.

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

What if cardiology were no longer an internal medicine subspecialty? Four leading cardiology societies have announced plans to create a new certification process that is independent of the American Board of Internal Medicine maintenance of certification (MOC) system.

As envisioned, the new “independent, self-governed” entity would supplant the ABIM’s long-standing and widely criticized MOC system and establish cardiology as its own specialty with its own subspecialties. Long in coming, it is only the latest response to many in the field who for years have charged that the MOC system is needlessly burdensome and expensive.

“It’s time to have a dedicated cardiovascular medicine board of our own,” said B. Hadley Wilson, MD, in the group’s announcement. “Cardiology is a distinct medical specialty, and physicians want and deserve a clinical competency and continuous certification program that is meaningful to their practice and patients.”

Hadley Wilson, Sanger Heart & Vascular Institute Vascular Kenilworth, Charlotte, N.C., is president of the American College of Cardiology, one of the four societies spearheading the initiative along with the Heart Failure Society of America, the Heart Rhythm Society, and the Society for Cardiovascular Angiography & Interventions.

Their Sept. 21 statement says that the consortium will apply to the American Board of Medical Specialties to request an independent cardiology board that follows a “new competency-based approach to continuous certification – one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

It continues, “The new board requirements will de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills.”

“The new board’s focus on competence in the pursuit of continuous certification is a needed paradigm shift for the field,” states HFSA President John R. Teerlink, MD, University of California, San Francisco, and the San Francisco VA Medical Center, in the announcement.

“I commend these professional cardiovascular societies for taking on this important challenge,” Deepak L. Bhatt, MD, MPH, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York City, told this news organization by email.

“This is an incredible opportunity to redefine what ongoing cardiovascular education means to the contemporary practicing cardiologist in a way that is relevant to improving the care of actual patients,” said Dr. Bhatt, who chairs the ACC Accreditation Oversight Committee.

“There needs to be an agile, personalized, convenient, and effective system to assist practitioners to stay current with new knowledge and demonstrate the necessary competencies,” Harlan Krumholz, MD, said in an email.

“There is a deep sense in the profession that the current approaches do not meet the needs of clinicians or society,” said Dr. Krumholz, Yale School of Medicine, New Haven, Conn., who has sat on the ABIM board of directors.

“This effort, which now will create competition, has the potential to spark innovation,” he said. “The key is that any approach needs to ask the question, ‘Is the cost and effort producing benefit for patients and society?’ If it is not, we have not found the right system.”

In a statement in response to the new development, ABIM said it plans to continue “offering and administering” its existing MOC programs across all specialties.

“Any physician choosing to maintain their ABIM certification in these disciplines will continue to have a pathway with ABIM to do so,” it says. “Questions about the cardiovascular organizations’ announcement and how it may affect individual physicians are best answered by those organizations.”

The process of approving the heart societies’ application to ABMS “is expected to take several months,” their announcement states. If approval is granted, “it will then take several additional months before initial certification and continuous certification and competency programs would begin.”

Medscape provides educational content including MOC. Medscape’s editorial content, including news and features, is developed independently of the educational content available on Medscape.

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

What if cardiology were no longer an internal medicine subspecialty? Four leading cardiology societies have announced plans to create a new certification process that is independent of the American Board of Internal Medicine maintenance of certification (MOC) system.

As envisioned, the new “independent, self-governed” entity would supplant the ABIM’s long-standing and widely criticized MOC system and establish cardiology as its own specialty with its own subspecialties. Long in coming, it is only the latest response to many in the field who for years have charged that the MOC system is needlessly burdensome and expensive.

“It’s time to have a dedicated cardiovascular medicine board of our own,” said B. Hadley Wilson, MD, in the group’s announcement. “Cardiology is a distinct medical specialty, and physicians want and deserve a clinical competency and continuous certification program that is meaningful to their practice and patients.”

Hadley Wilson, Sanger Heart & Vascular Institute Vascular Kenilworth, Charlotte, N.C., is president of the American College of Cardiology, one of the four societies spearheading the initiative along with the Heart Failure Society of America, the Heart Rhythm Society, and the Society for Cardiovascular Angiography & Interventions.

Their Sept. 21 statement says that the consortium will apply to the American Board of Medical Specialties to request an independent cardiology board that follows a “new competency-based approach to continuous certification – one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

It continues, “The new board requirements will de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills.”

“The new board’s focus on competence in the pursuit of continuous certification is a needed paradigm shift for the field,” states HFSA President John R. Teerlink, MD, University of California, San Francisco, and the San Francisco VA Medical Center, in the announcement.

“I commend these professional cardiovascular societies for taking on this important challenge,” Deepak L. Bhatt, MD, MPH, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York City, told this news organization by email.

“This is an incredible opportunity to redefine what ongoing cardiovascular education means to the contemporary practicing cardiologist in a way that is relevant to improving the care of actual patients,” said Dr. Bhatt, who chairs the ACC Accreditation Oversight Committee.

“There needs to be an agile, personalized, convenient, and effective system to assist practitioners to stay current with new knowledge and demonstrate the necessary competencies,” Harlan Krumholz, MD, said in an email.

“There is a deep sense in the profession that the current approaches do not meet the needs of clinicians or society,” said Dr. Krumholz, Yale School of Medicine, New Haven, Conn., who has sat on the ABIM board of directors.

“This effort, which now will create competition, has the potential to spark innovation,” he said. “The key is that any approach needs to ask the question, ‘Is the cost and effort producing benefit for patients and society?’ If it is not, we have not found the right system.”

In a statement in response to the new development, ABIM said it plans to continue “offering and administering” its existing MOC programs across all specialties.

“Any physician choosing to maintain their ABIM certification in these disciplines will continue to have a pathway with ABIM to do so,” it says. “Questions about the cardiovascular organizations’ announcement and how it may affect individual physicians are best answered by those organizations.”

The process of approving the heart societies’ application to ABMS “is expected to take several months,” their announcement states. If approval is granted, “it will then take several additional months before initial certification and continuous certification and competency programs would begin.”

Medscape provides educational content including MOC. Medscape’s editorial content, including news and features, is developed independently of the educational content available on Medscape.

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

A silent disorder is rising among older people worldwide, as millions unknowingly grapple with glaucoma, ophthalmologists warn.

It’s predicted that by 2050, the number of people with glaucoma will surge by more than 200%, highlighting an urgent need for heightened awareness, early detection, and advanced treatment strategies.

“That’s a lot of people with a blinding disease who don’t know they have it,” said Joel S. Schuman, MD, professor of ophthalmology and codirector of the Glaucoma Service at Wills Eye Hospital in Philadelphia. “Late in the disease, people may notice they’re tripping over the curb, or walking into things they didn’t see. It really is only in very advanced disease that people notice there’s anything wrong.”

Glaucoma is the second leading cause of blindness worldwide, affecting 3 million people in the United States, and yet half of those affected are unaware, according to the Centers for Disease Control and Prevention. 

Recent research at the University of Gothenburg in Sweden underscores glaucoma’s stealthy nature: Five percent of 560 70-year-olds had the disease, and half of those did not know they had it before they took part in the study. 

“Living with glaucoma, especially without realizing it, can be very isolating,” said Lena Havstam Johansson, a PhD student at the University of Gothenburg and a specialist nurse at Sahlgrenska University Hospital, who did the study. “It may lead people to stay at home to avoid the trouble.”

Once symptoms arise, some may notice patchy blind spots in their peripheral vision, and in their central vision in late stages.

While many people assume they are getting clumsier with age, Dr. Schuman said, they often have a condition that can be slowed with the right treatment. 

Though there are various types of the disease, about 9 in 10 people in the United States have primary open-angle glaucoma (POAG).  

It is most common among people over the age of 60, those with a family history of glaucoma, and people who have diabetes. It disproportionately affects Black people, who are six times more likely than are White people to have advanced vision loss from the disease. 

More than 120,000 people in the United States are blind from glaucoma, accounting for 9%-12% of all cases of blindness. Glaucoma treatments range from eye drops to laser treatments to surgery, all of which aim to reduce eye pressure. Some doctors will recommend oral medication along with eye drops.

“We have a lot of treatment options, and they work pretty well,” Dr. Schuman said. “But the first step is the person knowing they have glaucoma, and the second step is that person seeking care.

Rarer types of glaucoma include normal-tension glaucoma, which is more common among people of Japanese ancestry, and congenital glaucoma, which affects about 1 in 10,000 babies born in the United States.

The best way to ensure early detection and treatment is to get regular eye exams – every 2-4 years for adults under the age of 55, and annually thereafter, said Annie Wu, MD, clinical assistant professor of ophthalmology at the Kellogg Eye Center at the University of Michigan. 

The fact that glaucoma’s symptoms are slow to develop, coupled with a lack of access to eye specialists many Americans face, makes the disease even more dangerous. 

The University of Pennsylvania is among those trying to change that. The Philadelphia school has hosted free glaucoma screening programs for Black residents.  

There are a number of organizations that offer access to free glaucoma screening. 
 

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

A silent disorder is rising among older people worldwide, as millions unknowingly grapple with glaucoma, ophthalmologists warn.

It’s predicted that by 2050, the number of people with glaucoma will surge by more than 200%, highlighting an urgent need for heightened awareness, early detection, and advanced treatment strategies.

“That’s a lot of people with a blinding disease who don’t know they have it,” said Joel S. Schuman, MD, professor of ophthalmology and codirector of the Glaucoma Service at Wills Eye Hospital in Philadelphia. “Late in the disease, people may notice they’re tripping over the curb, or walking into things they didn’t see. It really is only in very advanced disease that people notice there’s anything wrong.”

Glaucoma is the second leading cause of blindness worldwide, affecting 3 million people in the United States, and yet half of those affected are unaware, according to the Centers for Disease Control and Prevention. 

Recent research at the University of Gothenburg in Sweden underscores glaucoma’s stealthy nature: Five percent of 560 70-year-olds had the disease, and half of those did not know they had it before they took part in the study. 

“Living with glaucoma, especially without realizing it, can be very isolating,” said Lena Havstam Johansson, a PhD student at the University of Gothenburg and a specialist nurse at Sahlgrenska University Hospital, who did the study. “It may lead people to stay at home to avoid the trouble.”

Once symptoms arise, some may notice patchy blind spots in their peripheral vision, and in their central vision in late stages.

While many people assume they are getting clumsier with age, Dr. Schuman said, they often have a condition that can be slowed with the right treatment. 

Though there are various types of the disease, about 9 in 10 people in the United States have primary open-angle glaucoma (POAG).  

It is most common among people over the age of 60, those with a family history of glaucoma, and people who have diabetes. It disproportionately affects Black people, who are six times more likely than are White people to have advanced vision loss from the disease. 

More than 120,000 people in the United States are blind from glaucoma, accounting for 9%-12% of all cases of blindness. Glaucoma treatments range from eye drops to laser treatments to surgery, all of which aim to reduce eye pressure. Some doctors will recommend oral medication along with eye drops.

“We have a lot of treatment options, and they work pretty well,” Dr. Schuman said. “But the first step is the person knowing they have glaucoma, and the second step is that person seeking care.

Rarer types of glaucoma include normal-tension glaucoma, which is more common among people of Japanese ancestry, and congenital glaucoma, which affects about 1 in 10,000 babies born in the United States.

The best way to ensure early detection and treatment is to get regular eye exams – every 2-4 years for adults under the age of 55, and annually thereafter, said Annie Wu, MD, clinical assistant professor of ophthalmology at the Kellogg Eye Center at the University of Michigan. 

The fact that glaucoma’s symptoms are slow to develop, coupled with a lack of access to eye specialists many Americans face, makes the disease even more dangerous. 

The University of Pennsylvania is among those trying to change that. The Philadelphia school has hosted free glaucoma screening programs for Black residents.  

There are a number of organizations that offer access to free glaucoma screening. 
 

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

A silent disorder is rising among older people worldwide, as millions unknowingly grapple with glaucoma, ophthalmologists warn.

It’s predicted that by 2050, the number of people with glaucoma will surge by more than 200%, highlighting an urgent need for heightened awareness, early detection, and advanced treatment strategies.

“That’s a lot of people with a blinding disease who don’t know they have it,” said Joel S. Schuman, MD, professor of ophthalmology and codirector of the Glaucoma Service at Wills Eye Hospital in Philadelphia. “Late in the disease, people may notice they’re tripping over the curb, or walking into things they didn’t see. It really is only in very advanced disease that people notice there’s anything wrong.”

Glaucoma is the second leading cause of blindness worldwide, affecting 3 million people in the United States, and yet half of those affected are unaware, according to the Centers for Disease Control and Prevention. 

Recent research at the University of Gothenburg in Sweden underscores glaucoma’s stealthy nature: Five percent of 560 70-year-olds had the disease, and half of those did not know they had it before they took part in the study. 

“Living with glaucoma, especially without realizing it, can be very isolating,” said Lena Havstam Johansson, a PhD student at the University of Gothenburg and a specialist nurse at Sahlgrenska University Hospital, who did the study. “It may lead people to stay at home to avoid the trouble.”

Once symptoms arise, some may notice patchy blind spots in their peripheral vision, and in their central vision in late stages.

While many people assume they are getting clumsier with age, Dr. Schuman said, they often have a condition that can be slowed with the right treatment. 

Though there are various types of the disease, about 9 in 10 people in the United States have primary open-angle glaucoma (POAG).  

It is most common among people over the age of 60, those with a family history of glaucoma, and people who have diabetes. It disproportionately affects Black people, who are six times more likely than are White people to have advanced vision loss from the disease. 

More than 120,000 people in the United States are blind from glaucoma, accounting for 9%-12% of all cases of blindness. Glaucoma treatments range from eye drops to laser treatments to surgery, all of which aim to reduce eye pressure. Some doctors will recommend oral medication along with eye drops.

“We have a lot of treatment options, and they work pretty well,” Dr. Schuman said. “But the first step is the person knowing they have glaucoma, and the second step is that person seeking care.

Rarer types of glaucoma include normal-tension glaucoma, which is more common among people of Japanese ancestry, and congenital glaucoma, which affects about 1 in 10,000 babies born in the United States.

The best way to ensure early detection and treatment is to get regular eye exams – every 2-4 years for adults under the age of 55, and annually thereafter, said Annie Wu, MD, clinical assistant professor of ophthalmology at the Kellogg Eye Center at the University of Michigan. 

The fact that glaucoma’s symptoms are slow to develop, coupled with a lack of access to eye specialists many Americans face, makes the disease even more dangerous. 

The University of Pennsylvania is among those trying to change that. The Philadelphia school has hosted free glaucoma screening programs for Black residents.  

There are a number of organizations that offer access to free glaucoma screening. 
 

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

TOPLINE:

A new study confirms the safety and efficacy of the psychedelic MDMA in ethnically and racially diverse populations with moderate to severe posttraumatic stress disorder.

METHODOLOGY:

Trauma-focused psychotherapies are the gold standard treatment for PTSD, which affects about 5% of Americans each year. However, many patients have persistent symptoms, and up to 47% don’t respond to the SSRIs sertraline and paroxetine, which are approved for PTSD by the Food and Drug Administration.

Mounting evidence suggests 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT), which promotes monoamine reuptake inhibition and release, simultaneously inducing prosocial feelings and softening responses to emotionally challenging and fearful stimuli, could be an alternative treatment for PTSD, possibly enhancing the benefits of psychotherapy.

A phase 3 study (MAPP1) showed MDMA-AT was generally well-tolerated and met the primary and secondary endpoints of reduced PTSD symptom severity and decreased functional impairment.

This new confirmatory phase 3 study (MAPP2) included 104 patients with PTSD who were randomized to MDMA-AT or placebo with therapy. Participants were a mean age of about 39 years, 71.2% were assigned female sex at birth, 33.7% identified as non-White, and 26.9% identified as Hispanic/Latino.

The mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score at baseline was 39.0 and was similar between groups. Overall, 26.9% and 73.1% of patients had moderate or severe PTSD, respectively.
 

TAKEAWAY:

Among the 94 participants who completed the study, the least-squares mean change in CAPS-5 total score at 18 weeks was −23.7 (95% confidence interval, −26.9 to −20.4) for MDMA-AT versus −14.8 (95% CI, −18.3 to −11.3) for placebo with therapy (treatment difference: −8.9; 95% CI, −13.7 to −4.1; P < .001).

MDMA-AT significantly mitigated the secondary outcome of clinician-rated functional impairment, as measured by a reduction in the Sheehan Disability Scale score.

About 86.5% of participants treated with MDMA-AT achieved a clinically meaningful benefit, and 71.2% no longer met criteria for PTSD by study end.

Treatment-emergent adverse events were mostly transient and mild or moderate in severity. Although suicidal ideation was reported in both groups, MDMA did not appear to increase the risk, and there were no reports of problematic MDMA abuse or dependence.
 

IN PRACTICE:

“This confirmatory phase 3 trial showed consistent benefits of MDMA-AT in an ethnoracially diverse group of individuals with long-standing moderate to severe PTSD and numerous comorbidities,” write the authors, noting the dropout rate was low and treatment was generally well tolerated.

SOURCE:

The study was conducted by Jennifer M. Mitchell, PhD, department of neurology and department of psychiatry and behavioral sciences, University of California, San Francisco, and colleagues. It was published online in Nature Medicine.

LIMITATIONS:

The study excluded participants with high suicide risk, comorbid personality disorders, and underlying cardiovascular disease. Effect sizes for MDMA-AT were similar to MAPP1 and, although higher than those observed in SSRI studies, the superiority of MDMA-AT over SSRIs cannot be assumed without a direct comparison.

DISCLOSURES:

The study was funded by the Multidisciplinary Association for Psychedelic Studies, with support from the Steven and Alexandra Cohen Foundation, and organized by the MAPS Public Benefit Corporation. Dr. Mitchell has reported receiving research support from MAPS; grants/contracts from the Veterans Administration and FDA; royalties/licenses from the University of California, Los Angeles; and payment/honoraria from Stanford University and Johns Hopkins. She has been a reviewer for the National Institute on Drug Abuse Clinical Trials Network, a member of the Research Advisory Panel for the California Department of Justice, and a grant reviewer for the Australian National Health and Medical Research Council.

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

TOPLINE:

A new study confirms the safety and efficacy of the psychedelic MDMA in ethnically and racially diverse populations with moderate to severe posttraumatic stress disorder.

METHODOLOGY:

Trauma-focused psychotherapies are the gold standard treatment for PTSD, which affects about 5% of Americans each year. However, many patients have persistent symptoms, and up to 47% don’t respond to the SSRIs sertraline and paroxetine, which are approved for PTSD by the Food and Drug Administration.

Mounting evidence suggests 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT), which promotes monoamine reuptake inhibition and release, simultaneously inducing prosocial feelings and softening responses to emotionally challenging and fearful stimuli, could be an alternative treatment for PTSD, possibly enhancing the benefits of psychotherapy.

A phase 3 study (MAPP1) showed MDMA-AT was generally well-tolerated and met the primary and secondary endpoints of reduced PTSD symptom severity and decreased functional impairment.

This new confirmatory phase 3 study (MAPP2) included 104 patients with PTSD who were randomized to MDMA-AT or placebo with therapy. Participants were a mean age of about 39 years, 71.2% were assigned female sex at birth, 33.7% identified as non-White, and 26.9% identified as Hispanic/Latino.

The mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score at baseline was 39.0 and was similar between groups. Overall, 26.9% and 73.1% of patients had moderate or severe PTSD, respectively.
 

TAKEAWAY:

Among the 94 participants who completed the study, the least-squares mean change in CAPS-5 total score at 18 weeks was −23.7 (95% confidence interval, −26.9 to −20.4) for MDMA-AT versus −14.8 (95% CI, −18.3 to −11.3) for placebo with therapy (treatment difference: −8.9; 95% CI, −13.7 to −4.1; P < .001).

MDMA-AT significantly mitigated the secondary outcome of clinician-rated functional impairment, as measured by a reduction in the Sheehan Disability Scale score.

About 86.5% of participants treated with MDMA-AT achieved a clinically meaningful benefit, and 71.2% no longer met criteria for PTSD by study end.

Treatment-emergent adverse events were mostly transient and mild or moderate in severity. Although suicidal ideation was reported in both groups, MDMA did not appear to increase the risk, and there were no reports of problematic MDMA abuse or dependence.
 

IN PRACTICE:

“This confirmatory phase 3 trial showed consistent benefits of MDMA-AT in an ethnoracially diverse group of individuals with long-standing moderate to severe PTSD and numerous comorbidities,” write the authors, noting the dropout rate was low and treatment was generally well tolerated.

SOURCE:

The study was conducted by Jennifer M. Mitchell, PhD, department of neurology and department of psychiatry and behavioral sciences, University of California, San Francisco, and colleagues. It was published online in Nature Medicine.

LIMITATIONS:

The study excluded participants with high suicide risk, comorbid personality disorders, and underlying cardiovascular disease. Effect sizes for MDMA-AT were similar to MAPP1 and, although higher than those observed in SSRI studies, the superiority of MDMA-AT over SSRIs cannot be assumed without a direct comparison.

DISCLOSURES:

The study was funded by the Multidisciplinary Association for Psychedelic Studies, with support from the Steven and Alexandra Cohen Foundation, and organized by the MAPS Public Benefit Corporation. Dr. Mitchell has reported receiving research support from MAPS; grants/contracts from the Veterans Administration and FDA; royalties/licenses from the University of California, Los Angeles; and payment/honoraria from Stanford University and Johns Hopkins. She has been a reviewer for the National Institute on Drug Abuse Clinical Trials Network, a member of the Research Advisory Panel for the California Department of Justice, and a grant reviewer for the Australian National Health and Medical Research Council.

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

TOPLINE:

A new study confirms the safety and efficacy of the psychedelic MDMA in ethnically and racially diverse populations with moderate to severe posttraumatic stress disorder.

METHODOLOGY:

Trauma-focused psychotherapies are the gold standard treatment for PTSD, which affects about 5% of Americans each year. However, many patients have persistent symptoms, and up to 47% don’t respond to the SSRIs sertraline and paroxetine, which are approved for PTSD by the Food and Drug Administration.

Mounting evidence suggests 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT), which promotes monoamine reuptake inhibition and release, simultaneously inducing prosocial feelings and softening responses to emotionally challenging and fearful stimuli, could be an alternative treatment for PTSD, possibly enhancing the benefits of psychotherapy.

A phase 3 study (MAPP1) showed MDMA-AT was generally well-tolerated and met the primary and secondary endpoints of reduced PTSD symptom severity and decreased functional impairment.

This new confirmatory phase 3 study (MAPP2) included 104 patients with PTSD who were randomized to MDMA-AT or placebo with therapy. Participants were a mean age of about 39 years, 71.2% were assigned female sex at birth, 33.7% identified as non-White, and 26.9% identified as Hispanic/Latino.

The mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score at baseline was 39.0 and was similar between groups. Overall, 26.9% and 73.1% of patients had moderate or severe PTSD, respectively.
 

TAKEAWAY:

Among the 94 participants who completed the study, the least-squares mean change in CAPS-5 total score at 18 weeks was −23.7 (95% confidence interval, −26.9 to −20.4) for MDMA-AT versus −14.8 (95% CI, −18.3 to −11.3) for placebo with therapy (treatment difference: −8.9; 95% CI, −13.7 to −4.1; P < .001).

MDMA-AT significantly mitigated the secondary outcome of clinician-rated functional impairment, as measured by a reduction in the Sheehan Disability Scale score.

About 86.5% of participants treated with MDMA-AT achieved a clinically meaningful benefit, and 71.2% no longer met criteria for PTSD by study end.

Treatment-emergent adverse events were mostly transient and mild or moderate in severity. Although suicidal ideation was reported in both groups, MDMA did not appear to increase the risk, and there were no reports of problematic MDMA abuse or dependence.
 

IN PRACTICE:

“This confirmatory phase 3 trial showed consistent benefits of MDMA-AT in an ethnoracially diverse group of individuals with long-standing moderate to severe PTSD and numerous comorbidities,” write the authors, noting the dropout rate was low and treatment was generally well tolerated.

SOURCE:

The study was conducted by Jennifer M. Mitchell, PhD, department of neurology and department of psychiatry and behavioral sciences, University of California, San Francisco, and colleagues. It was published online in Nature Medicine.

LIMITATIONS:

The study excluded participants with high suicide risk, comorbid personality disorders, and underlying cardiovascular disease. Effect sizes for MDMA-AT were similar to MAPP1 and, although higher than those observed in SSRI studies, the superiority of MDMA-AT over SSRIs cannot be assumed without a direct comparison.

DISCLOSURES:

The study was funded by the Multidisciplinary Association for Psychedelic Studies, with support from the Steven and Alexandra Cohen Foundation, and organized by the MAPS Public Benefit Corporation. Dr. Mitchell has reported receiving research support from MAPS; grants/contracts from the Veterans Administration and FDA; royalties/licenses from the University of California, Los Angeles; and payment/honoraria from Stanford University and Johns Hopkins. She has been a reviewer for the National Institute on Drug Abuse Clinical Trials Network, a member of the Research Advisory Panel for the California Department of Justice, and a grant reviewer for the Australian National Health and Medical Research Council.

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

Taking creatine as a supplement for 6 months appears to significantly improve clinical features of post–COVID-19 fatigue syndrome (PVFS or long COVID), a small randomized, placebo-controlled, double-blinded study suggests.

Researchers, led by Jelena Slankamenac, with Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, Serbia, published their findings in Food, Science & Nutrition .

“This is the first human study known to the authors that evaluated the efficacy and safety of supplemental creatine for fatigue, tissue bioenergetics, and patient-reported outcomes in patients with post–COVID-19 fatigue syndrome,” the authors write.

They say the findings may be attributed to creatine’s “energy-replenishing and neuroprotective activity.”
 

Significant reductions in symptoms

Researchers randomized the 12 participants into two groups of 6 each. The creatine group received 4 g creatine monohydrate per day, while the placebo group received the same amount of inulin.

At 3 months, dietary creatine supplements produced a significant reduction in fatigue, compared with baseline values ( P = .04) and significantly improved scores for several long COVID–related symptoms, including loss of taste, breathing difficulties, body aches, headache, and difficulties concentrating) ( P < .05), the researchers report.

Intervention effect sizes were assessed by Cohen statistics, with a d of at least 0.8 indicating a large effect.

Among highlights of the results were that patients reported a significant 77.8% drop in scores for concentration difficulties at the 3-month follow-up (Cohen’s effect, d = 1.19) and no concentration difficulties at the 6-month follow-up (Cohen’s effect, d = 2.46).

Total creatine levels increased in several locations across the brain (as much as 33% for right parietal white matter). No changes in tissue creatine levels were found in the placebo group during the trial.

“Since PVFS is characterized by impaired tissue bioenergetics ..., supplemental creatine might be an effective dietary intervention to uphold brain creatine in post–COVID-19 fatigue syndrome,” the authors write.

The authors add that creatine supplements for long COVID patients could benefit organs beyond the brain as participants saw “a significant drop in lung and body pain after the intervention.”
 

Unanswered questions

Some experts said the results should be interpreted with caution.

“This research paper is very interesting,” says Nisha Viswanathan, MD, director of the long COVID program at University of California, Los Angeles, “but the limited number of patients makes the results difficult to generalize.”

Dr. Viswanathan, who was not part of the study, pointed out that the patients included in this study had a recent COVID infection (under 3 months).

“Acute COVID infection can take up to 3 months to resolve,” she says. “We define patients with long COVID as those with symptoms lasting greater than 3 months. Therefore, these patients could have had improvements in their fatigue due to the natural course of the illness rather than creatine supplementation.”

Alba Azola, MD, assistant professor in the department of physical medicine and rehabilitation at Johns Hopkins University, Baltimore, said she also was troubled by the window of 3 months for recent COVID infection.

She said she would like to see results for patients who have ongoing symptoms for at least 6 months after infection, especially given creatine supplements’ history in research.

Creatine supplements for other conditions, such as fibromyalgia and chronic fatigue syndrome, have been tested for nearly 2 decades, she pointed out, with conflicting findings, something the authors acknowledge in the paper.

“I think it’s premature to say (creatine) is the key,” she says. She added that the small sample size is important to consider given the heterogeneity of patients with long COVID.

That said, Dr. Azola says, she applauds all efforts to find treatments for long COVID, especially randomized, controlled studies like this one.
 

No major side effects

No major side effects were reported for either intervention, except for transient mild nausea reported by one patient after taking creatine.

Compliance with the intervention was 90.6% ± 3.5% in the creatine group and 95.3% ± 5.0% in the control group (P = .04).

Participants were eligible for inclusion if they were 18-65 years old, had a positive COVID test within the last 3 months (documented by a valid polymerase chain reaction [PCR] or antigen test performed in a COVID-19–certified lab); had moderate to severe fatigue; and at least one additional COVID-related symptom, including loss of taste or smell, breathing trouble, lung pain, body aches, headaches, or difficulties concentrating.

The authors acknowledge that they selected a sample of young to middle-aged adults experiencing moderate long COVID symptoms, and it’s unknown whether creatine is equally effective in other PVFS populations, such as elderly people, children, or patients with less or more severe disease.

Senior author Dr. Sergei Ostojic serves as a member of the Scientific Advisory Board on creatine in health and medicine (AlzChem LLC). He co-owns a patent for “Supplements Based on Liquid Creatine” at the European Patent Office. He has received research support related to creatine during the past 36 months from the Serbian Ministry of Education, Science, and Technological Development; Provincial Secretariat for Higher Education and Scientific Research; Alzchem GmbH; ThermoLife International; and Hueston Hennigan LLP. He does not own stocks and shares in any organization. Other authors declare no known relevant financial interests. Dr. Viswanathan and Dr. Azola report no relevant financial relationships.
 

Taking creatine as a supplement for 6 months appears to significantly improve clinical features of post–COVID-19 fatigue syndrome (PVFS or long COVID), a small randomized, placebo-controlled, double-blinded study suggests.

Researchers, led by Jelena Slankamenac, with Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, Serbia, published their findings in Food, Science & Nutrition .

“This is the first human study known to the authors that evaluated the efficacy and safety of supplemental creatine for fatigue, tissue bioenergetics, and patient-reported outcomes in patients with post–COVID-19 fatigue syndrome,” the authors write.

They say the findings may be attributed to creatine’s “energy-replenishing and neuroprotective activity.”
 

Significant reductions in symptoms

Researchers randomized the 12 participants into two groups of 6 each. The creatine group received 4 g creatine monohydrate per day, while the placebo group received the same amount of inulin.

At 3 months, dietary creatine supplements produced a significant reduction in fatigue, compared with baseline values ( P = .04) and significantly improved scores for several long COVID–related symptoms, including loss of taste, breathing difficulties, body aches, headache, and difficulties concentrating) ( P < .05), the researchers report.

Intervention effect sizes were assessed by Cohen statistics, with a d of at least 0.8 indicating a large effect.

Among highlights of the results were that patients reported a significant 77.8% drop in scores for concentration difficulties at the 3-month follow-up (Cohen’s effect, d = 1.19) and no concentration difficulties at the 6-month follow-up (Cohen’s effect, d = 2.46).

Total creatine levels increased in several locations across the brain (as much as 33% for right parietal white matter). No changes in tissue creatine levels were found in the placebo group during the trial.

“Since PVFS is characterized by impaired tissue bioenergetics ..., supplemental creatine might be an effective dietary intervention to uphold brain creatine in post–COVID-19 fatigue syndrome,” the authors write.

The authors add that creatine supplements for long COVID patients could benefit organs beyond the brain as participants saw “a significant drop in lung and body pain after the intervention.”
 

Unanswered questions

Some experts said the results should be interpreted with caution.

“This research paper is very interesting,” says Nisha Viswanathan, MD, director of the long COVID program at University of California, Los Angeles, “but the limited number of patients makes the results difficult to generalize.”

Dr. Viswanathan, who was not part of the study, pointed out that the patients included in this study had a recent COVID infection (under 3 months).

“Acute COVID infection can take up to 3 months to resolve,” she says. “We define patients with long COVID as those with symptoms lasting greater than 3 months. Therefore, these patients could have had improvements in their fatigue due to the natural course of the illness rather than creatine supplementation.”

Alba Azola, MD, assistant professor in the department of physical medicine and rehabilitation at Johns Hopkins University, Baltimore, said she also was troubled by the window of 3 months for recent COVID infection.

She said she would like to see results for patients who have ongoing symptoms for at least 6 months after infection, especially given creatine supplements’ history in research.

Creatine supplements for other conditions, such as fibromyalgia and chronic fatigue syndrome, have been tested for nearly 2 decades, she pointed out, with conflicting findings, something the authors acknowledge in the paper.

“I think it’s premature to say (creatine) is the key,” she says. She added that the small sample size is important to consider given the heterogeneity of patients with long COVID.

That said, Dr. Azola says, she applauds all efforts to find treatments for long COVID, especially randomized, controlled studies like this one.
 

No major side effects

No major side effects were reported for either intervention, except for transient mild nausea reported by one patient after taking creatine.

Compliance with the intervention was 90.6% ± 3.5% in the creatine group and 95.3% ± 5.0% in the control group (P = .04).

Participants were eligible for inclusion if they were 18-65 years old, had a positive COVID test within the last 3 months (documented by a valid polymerase chain reaction [PCR] or antigen test performed in a COVID-19–certified lab); had moderate to severe fatigue; and at least one additional COVID-related symptom, including loss of taste or smell, breathing trouble, lung pain, body aches, headaches, or difficulties concentrating.

The authors acknowledge that they selected a sample of young to middle-aged adults experiencing moderate long COVID symptoms, and it’s unknown whether creatine is equally effective in other PVFS populations, such as elderly people, children, or patients with less or more severe disease.

Senior author Dr. Sergei Ostojic serves as a member of the Scientific Advisory Board on creatine in health and medicine (AlzChem LLC). He co-owns a patent for “Supplements Based on Liquid Creatine” at the European Patent Office. He has received research support related to creatine during the past 36 months from the Serbian Ministry of Education, Science, and Technological Development; Provincial Secretariat for Higher Education and Scientific Research; Alzchem GmbH; ThermoLife International; and Hueston Hennigan LLP. He does not own stocks and shares in any organization. Other authors declare no known relevant financial interests. Dr. Viswanathan and Dr. Azola report no relevant financial relationships.
 

Taking creatine as a supplement for 6 months appears to significantly improve clinical features of post–COVID-19 fatigue syndrome (PVFS or long COVID), a small randomized, placebo-controlled, double-blinded study suggests.

Researchers, led by Jelena Slankamenac, with Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, Serbia, published their findings in Food, Science & Nutrition .

“This is the first human study known to the authors that evaluated the efficacy and safety of supplemental creatine for fatigue, tissue bioenergetics, and patient-reported outcomes in patients with post–COVID-19 fatigue syndrome,” the authors write.

They say the findings may be attributed to creatine’s “energy-replenishing and neuroprotective activity.”
 

Significant reductions in symptoms

Researchers randomized the 12 participants into two groups of 6 each. The creatine group received 4 g creatine monohydrate per day, while the placebo group received the same amount of inulin.

At 3 months, dietary creatine supplements produced a significant reduction in fatigue, compared with baseline values ( P = .04) and significantly improved scores for several long COVID–related symptoms, including loss of taste, breathing difficulties, body aches, headache, and difficulties concentrating) ( P < .05), the researchers report.

Intervention effect sizes were assessed by Cohen statistics, with a d of at least 0.8 indicating a large effect.

Among highlights of the results were that patients reported a significant 77.8% drop in scores for concentration difficulties at the 3-month follow-up (Cohen’s effect, d = 1.19) and no concentration difficulties at the 6-month follow-up (Cohen’s effect, d = 2.46).

Total creatine levels increased in several locations across the brain (as much as 33% for right parietal white matter). No changes in tissue creatine levels were found in the placebo group during the trial.

“Since PVFS is characterized by impaired tissue bioenergetics ..., supplemental creatine might be an effective dietary intervention to uphold brain creatine in post–COVID-19 fatigue syndrome,” the authors write.

The authors add that creatine supplements for long COVID patients could benefit organs beyond the brain as participants saw “a significant drop in lung and body pain after the intervention.”
 

Unanswered questions

Some experts said the results should be interpreted with caution.

“This research paper is very interesting,” says Nisha Viswanathan, MD, director of the long COVID program at University of California, Los Angeles, “but the limited number of patients makes the results difficult to generalize.”

Dr. Viswanathan, who was not part of the study, pointed out that the patients included in this study had a recent COVID infection (under 3 months).

“Acute COVID infection can take up to 3 months to resolve,” she says. “We define patients with long COVID as those with symptoms lasting greater than 3 months. Therefore, these patients could have had improvements in their fatigue due to the natural course of the illness rather than creatine supplementation.”

Alba Azola, MD, assistant professor in the department of physical medicine and rehabilitation at Johns Hopkins University, Baltimore, said she also was troubled by the window of 3 months for recent COVID infection.

She said she would like to see results for patients who have ongoing symptoms for at least 6 months after infection, especially given creatine supplements’ history in research.

Creatine supplements for other conditions, such as fibromyalgia and chronic fatigue syndrome, have been tested for nearly 2 decades, she pointed out, with conflicting findings, something the authors acknowledge in the paper.

“I think it’s premature to say (creatine) is the key,” she says. She added that the small sample size is important to consider given the heterogeneity of patients with long COVID.

That said, Dr. Azola says, she applauds all efforts to find treatments for long COVID, especially randomized, controlled studies like this one.
 

No major side effects

No major side effects were reported for either intervention, except for transient mild nausea reported by one patient after taking creatine.

Compliance with the intervention was 90.6% ± 3.5% in the creatine group and 95.3% ± 5.0% in the control group (P = .04).

Participants were eligible for inclusion if they were 18-65 years old, had a positive COVID test within the last 3 months (documented by a valid polymerase chain reaction [PCR] or antigen test performed in a COVID-19–certified lab); had moderate to severe fatigue; and at least one additional COVID-related symptom, including loss of taste or smell, breathing trouble, lung pain, body aches, headaches, or difficulties concentrating.

The authors acknowledge that they selected a sample of young to middle-aged adults experiencing moderate long COVID symptoms, and it’s unknown whether creatine is equally effective in other PVFS populations, such as elderly people, children, or patients with less or more severe disease.

Senior author Dr. Sergei Ostojic serves as a member of the Scientific Advisory Board on creatine in health and medicine (AlzChem LLC). He co-owns a patent for “Supplements Based on Liquid Creatine” at the European Patent Office. He has received research support related to creatine during the past 36 months from the Serbian Ministry of Education, Science, and Technological Development; Provincial Secretariat for Higher Education and Scientific Research; Alzchem GmbH; ThermoLife International; and Hueston Hennigan LLP. He does not own stocks and shares in any organization. Other authors declare no known relevant financial interests. Dr. Viswanathan and Dr. Azola report no relevant financial relationships.
 

Exercising in the morning may have the biggest impact on the likelihood of having obesity, whereas morning and afternoon exercise appear to reduce the risk of developing type 2 diabetes, suggest two studies.

Tongyu Ma, PhD, research assistant professor with the Health Sciences Department, Franklin Pierce University, Rindge, N.H., and colleagues studied data on almost 5,300 individuals, finding a strong association between moderate to vigorous physical activity (MVPA) and obesity.

The research, published in Obesity, showed that people who exercised in the morning had a lower body mass index than that of those who exercised at other times, even though they were more sedentary.

For the second study, Chirag J. Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, and colleagues examined more than 93,000 individuals and found that morning and afternoon, but not evening, exercise reduced the risk for type 2 diabetes.

However, the results, published in Diabetologia, also indicated that people who undertook at least MVPA were protected against developing type 2 diabetes no matter what time of day they exercised.

Along with considering the timing of exercise, the authors suggest that it is “helpful to include some higher intensity activity to help reduce the risk of developing diabetes and other cardiovascular disease.”
 

Morning exercisers perform less physical activity

Dr. Ma and colleagues noted that “although a beneficial association among the levels of physical activity with obesity has been frequently reported, the optimal timing of physical activity for decreasing obesity remains controversial.”

The researchers analyzed data from the National Health and Nutrition Examination Survey for the 2003-2004 and 2005-2006 cycles, because accelerometry was implemented in those periods.

They included 5,285 individuals aged ≥ 20 years who had physical activity measured via an accelerometer worn on the right hip during waking hours for 7 consecutive days.

The diurnal pattern of MVPA was classified into three clusters by the established technique of K-means clustering analysis: morning (n = 642), midday (n = 2,456), and evening (n = 2,187).

The association between MVPA, diurnal pattern, and obesity was then assessed in linear regression models taking into account a range of potential confounding factors.

Overall, participants in the morning cluster were older and more likely to be female than those in the other clusters (P < .001 for both). They were also more likely to be nonsmokers (P = .007) and to have less than high school education (P = .0041).

Morning cluster individuals performed less physical activity and were more sedentary than those in the midday and evening groups (P < .001 for both), although they were more likely to be healthy eaters (P = .004), with a lower calorie intake (P < .001).

Individuals in the morning cluster had, on average, a lower body mass index than those in other clusters, at 27.4 vs. 28.4 in the midday cluster and 28.2 in the evening cluster (P for interaction = .02).

Morning cluster participants also had a lower waist circumference than participants in the midday or evening cluster: 95.9 cm, 97.9 cm, and 97.3 cm, respectively (P for interaction = .06).

The team reported that there was a strong linear association between MVPA and obesity in the morning cluster, whereas there was a weaker curvilinear association in the midday and evening clusters.

“This is exciting new research that is consistent with a common tip for meeting exercise goals – that is, schedule exercise in the morning before emails, phone calls, or meetings that might distract you,” Rebecca Krukowski, PhD, professor, public health sciences, University of Virginia, Charlottesville, said in a release.

However, she noted that the cross-sectional nature of the study means that it is “not known whether people who exercise consistently in the morning may be systematically different from those who exercise at other times, in ways that were not measured in this study.

“For example, people who exercise regularly in the morning could have more predictable schedules, such as being less likely to be shift workers or less likely to have caregiving responsibilities that impede morning exercise,” said Dr. Krukowski, who was not involved in the study.
 

No association between evening activity and type 2 diabetes risk

In the second study, the team studied 93,095 persons in the UK Biobank, with a mean age of 62 years and no history of type 2 diabetes, who wore a wrist accelerometer for 1 week.

The movement data were used to estimate the metabolic equivalent of task, which was then summed into the total physical activity completed in the morning, afternoon, and evening and linked to the development of incident type 2 diabetes.

After adjustment for potential confounding factors, both morning and afternoon physical activity were associated with a reduced risk of developing type 2 diabetes, at hazard ratios of 0.90 (P = 7 × 10-8) and 0.91 (P = 1 × 10-5), respectively.

However, there was no association between evening activity and the risk for type 2 diabetes, at a hazard ratio of 0.95 (P = .07).

The team found, however, that MVPA and vigorous physical activity were associated with a reduced risk for type 2 diabetes at all times of day.

Dr. Patel’s study was supported in part by National Institutes of Health grants. No other funding was declared. No relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

Exercising in the morning may have the biggest impact on the likelihood of having obesity, whereas morning and afternoon exercise appear to reduce the risk of developing type 2 diabetes, suggest two studies.

Tongyu Ma, PhD, research assistant professor with the Health Sciences Department, Franklin Pierce University, Rindge, N.H., and colleagues studied data on almost 5,300 individuals, finding a strong association between moderate to vigorous physical activity (MVPA) and obesity.

The research, published in Obesity, showed that people who exercised in the morning had a lower body mass index than that of those who exercised at other times, even though they were more sedentary.

For the second study, Chirag J. Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, and colleagues examined more than 93,000 individuals and found that morning and afternoon, but not evening, exercise reduced the risk for type 2 diabetes.

However, the results, published in Diabetologia, also indicated that people who undertook at least MVPA were protected against developing type 2 diabetes no matter what time of day they exercised.

Along with considering the timing of exercise, the authors suggest that it is “helpful to include some higher intensity activity to help reduce the risk of developing diabetes and other cardiovascular disease.”
 

Morning exercisers perform less physical activity

Dr. Ma and colleagues noted that “although a beneficial association among the levels of physical activity with obesity has been frequently reported, the optimal timing of physical activity for decreasing obesity remains controversial.”

The researchers analyzed data from the National Health and Nutrition Examination Survey for the 2003-2004 and 2005-2006 cycles, because accelerometry was implemented in those periods.

They included 5,285 individuals aged ≥ 20 years who had physical activity measured via an accelerometer worn on the right hip during waking hours for 7 consecutive days.

The diurnal pattern of MVPA was classified into three clusters by the established technique of K-means clustering analysis: morning (n = 642), midday (n = 2,456), and evening (n = 2,187).

The association between MVPA, diurnal pattern, and obesity was then assessed in linear regression models taking into account a range of potential confounding factors.

Overall, participants in the morning cluster were older and more likely to be female than those in the other clusters (P < .001 for both). They were also more likely to be nonsmokers (P = .007) and to have less than high school education (P = .0041).

Morning cluster individuals performed less physical activity and were more sedentary than those in the midday and evening groups (P < .001 for both), although they were more likely to be healthy eaters (P = .004), with a lower calorie intake (P < .001).

Individuals in the morning cluster had, on average, a lower body mass index than those in other clusters, at 27.4 vs. 28.4 in the midday cluster and 28.2 in the evening cluster (P for interaction = .02).

Morning cluster participants also had a lower waist circumference than participants in the midday or evening cluster: 95.9 cm, 97.9 cm, and 97.3 cm, respectively (P for interaction = .06).

The team reported that there was a strong linear association between MVPA and obesity in the morning cluster, whereas there was a weaker curvilinear association in the midday and evening clusters.

“This is exciting new research that is consistent with a common tip for meeting exercise goals – that is, schedule exercise in the morning before emails, phone calls, or meetings that might distract you,” Rebecca Krukowski, PhD, professor, public health sciences, University of Virginia, Charlottesville, said in a release.

However, she noted that the cross-sectional nature of the study means that it is “not known whether people who exercise consistently in the morning may be systematically different from those who exercise at other times, in ways that were not measured in this study.

“For example, people who exercise regularly in the morning could have more predictable schedules, such as being less likely to be shift workers or less likely to have caregiving responsibilities that impede morning exercise,” said Dr. Krukowski, who was not involved in the study.
 

No association between evening activity and type 2 diabetes risk

In the second study, the team studied 93,095 persons in the UK Biobank, with a mean age of 62 years and no history of type 2 diabetes, who wore a wrist accelerometer for 1 week.

The movement data were used to estimate the metabolic equivalent of task, which was then summed into the total physical activity completed in the morning, afternoon, and evening and linked to the development of incident type 2 diabetes.

After adjustment for potential confounding factors, both morning and afternoon physical activity were associated with a reduced risk of developing type 2 diabetes, at hazard ratios of 0.90 (P = 7 × 10-8) and 0.91 (P = 1 × 10-5), respectively.

However, there was no association between evening activity and the risk for type 2 diabetes, at a hazard ratio of 0.95 (P = .07).

The team found, however, that MVPA and vigorous physical activity were associated with a reduced risk for type 2 diabetes at all times of day.

Dr. Patel’s study was supported in part by National Institutes of Health grants. No other funding was declared. No relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

Exercising in the morning may have the biggest impact on the likelihood of having obesity, whereas morning and afternoon exercise appear to reduce the risk of developing type 2 diabetes, suggest two studies.

Tongyu Ma, PhD, research assistant professor with the Health Sciences Department, Franklin Pierce University, Rindge, N.H., and colleagues studied data on almost 5,300 individuals, finding a strong association between moderate to vigorous physical activity (MVPA) and obesity.

The research, published in Obesity, showed that people who exercised in the morning had a lower body mass index than that of those who exercised at other times, even though they were more sedentary.

For the second study, Chirag J. Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, and colleagues examined more than 93,000 individuals and found that morning and afternoon, but not evening, exercise reduced the risk for type 2 diabetes.

However, the results, published in Diabetologia, also indicated that people who undertook at least MVPA were protected against developing type 2 diabetes no matter what time of day they exercised.

Along with considering the timing of exercise, the authors suggest that it is “helpful to include some higher intensity activity to help reduce the risk of developing diabetes and other cardiovascular disease.”
 

Morning exercisers perform less physical activity

Dr. Ma and colleagues noted that “although a beneficial association among the levels of physical activity with obesity has been frequently reported, the optimal timing of physical activity for decreasing obesity remains controversial.”

The researchers analyzed data from the National Health and Nutrition Examination Survey for the 2003-2004 and 2005-2006 cycles, because accelerometry was implemented in those periods.

They included 5,285 individuals aged ≥ 20 years who had physical activity measured via an accelerometer worn on the right hip during waking hours for 7 consecutive days.

The diurnal pattern of MVPA was classified into three clusters by the established technique of K-means clustering analysis: morning (n = 642), midday (n = 2,456), and evening (n = 2,187).

The association between MVPA, diurnal pattern, and obesity was then assessed in linear regression models taking into account a range of potential confounding factors.

Overall, participants in the morning cluster were older and more likely to be female than those in the other clusters (P < .001 for both). They were also more likely to be nonsmokers (P = .007) and to have less than high school education (P = .0041).

Morning cluster individuals performed less physical activity and were more sedentary than those in the midday and evening groups (P < .001 for both), although they were more likely to be healthy eaters (P = .004), with a lower calorie intake (P < .001).

Individuals in the morning cluster had, on average, a lower body mass index than those in other clusters, at 27.4 vs. 28.4 in the midday cluster and 28.2 in the evening cluster (P for interaction = .02).

Morning cluster participants also had a lower waist circumference than participants in the midday or evening cluster: 95.9 cm, 97.9 cm, and 97.3 cm, respectively (P for interaction = .06).

The team reported that there was a strong linear association between MVPA and obesity in the morning cluster, whereas there was a weaker curvilinear association in the midday and evening clusters.

“This is exciting new research that is consistent with a common tip for meeting exercise goals – that is, schedule exercise in the morning before emails, phone calls, or meetings that might distract you,” Rebecca Krukowski, PhD, professor, public health sciences, University of Virginia, Charlottesville, said in a release.

However, she noted that the cross-sectional nature of the study means that it is “not known whether people who exercise consistently in the morning may be systematically different from those who exercise at other times, in ways that were not measured in this study.

“For example, people who exercise regularly in the morning could have more predictable schedules, such as being less likely to be shift workers or less likely to have caregiving responsibilities that impede morning exercise,” said Dr. Krukowski, who was not involved in the study.
 

No association between evening activity and type 2 diabetes risk

In the second study, the team studied 93,095 persons in the UK Biobank, with a mean age of 62 years and no history of type 2 diabetes, who wore a wrist accelerometer for 1 week.

The movement data were used to estimate the metabolic equivalent of task, which was then summed into the total physical activity completed in the morning, afternoon, and evening and linked to the development of incident type 2 diabetes.

After adjustment for potential confounding factors, both morning and afternoon physical activity were associated with a reduced risk of developing type 2 diabetes, at hazard ratios of 0.90 (P = 7 × 10-8) and 0.91 (P = 1 × 10-5), respectively.

However, there was no association between evening activity and the risk for type 2 diabetes, at a hazard ratio of 0.95 (P = .07).

The team found, however, that MVPA and vigorous physical activity were associated with a reduced risk for type 2 diabetes at all times of day.

Dr. Patel’s study was supported in part by National Institutes of Health grants. No other funding was declared. No relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

Sirisha Manyam, DO, eagerly looks forward to attending Association of VA Hematology and Oncology (AVAHO) 2023 and participating in discussion concerning two central topics: women's health and clinician wellness. Recognizing and meeting the distinctive stressors faced by healthcare workers, which have produced alarming rates of burnout, is an apt priority for Veterans Affairs systems, Dr Maryam suggests, and one which is paralleled by the need to engage the unique challenges faced by women, specifically the cluster of considerations surrounding breast cancer treatment.

Sirisha Manyam, DO, eagerly looks forward to attending Association of VA Hematology and Oncology (AVAHO) 2023 and participating in discussion concerning two central topics: women's health and clinician wellness. Recognizing and meeting the distinctive stressors faced by healthcare workers, which have produced alarming rates of burnout, is an apt priority for Veterans Affairs systems, Dr Maryam suggests, and one which is paralleled by the need to engage the unique challenges faced by women, specifically the cluster of considerations surrounding breast cancer treatment.

Sirisha Manyam, DO, eagerly looks forward to attending Association of VA Hematology and Oncology (AVAHO) 2023 and participating in discussion concerning two central topics: women's health and clinician wellness. Recognizing and meeting the distinctive stressors faced by healthcare workers, which have produced alarming rates of burnout, is an apt priority for Veterans Affairs systems, Dr Maryam suggests, and one which is paralleled by the need to engage the unique challenges faced by women, specifically the cluster of considerations surrounding breast cancer treatment.

Timothy O'Brien, MD, shares his expectations for the upcoming 2023 AVAHO conference. Dr O'Brien highlights four key areas of interest: networking with providers from other VA systems; creating more clinical trial opportunities; exploring educational sessions on topics like AI in oncology and geriatric oncology; and fostering team building within the local VA group. With an area of focus in malignant hematology, particularly multiple myeloma, Dr O'Brien sees learning opportunities within the education sessions on geriatric oncology. Considering that the average age of patients with multiple myeloma at his institution is 70 years, he looks forward to gaining valuable strategies for geriatric assessment.

Timothy O'Brien, MD, shares his expectations for the upcoming 2023 AVAHO conference. Dr O'Brien highlights four key areas of interest: networking with providers from other VA systems; creating more clinical trial opportunities; exploring educational sessions on topics like AI in oncology and geriatric oncology; and fostering team building within the local VA group. With an area of focus in malignant hematology, particularly multiple myeloma, Dr O'Brien sees learning opportunities within the education sessions on geriatric oncology. Considering that the average age of patients with multiple myeloma at his institution is 70 years, he looks forward to gaining valuable strategies for geriatric assessment.

Timothy O'Brien, MD, shares his expectations for the upcoming 2023 AVAHO conference. Dr O'Brien highlights four key areas of interest: networking with providers from other VA systems; creating more clinical trial opportunities; exploring educational sessions on topics like AI in oncology and geriatric oncology; and fostering team building within the local VA group. With an area of focus in malignant hematology, particularly multiple myeloma, Dr O'Brien sees learning opportunities within the education sessions on geriatric oncology. Considering that the average age of patients with multiple myeloma at his institution is 70 years, he looks forward to gaining valuable strategies for geriatric assessment.

Soo Park, MD, discusses her expectations for the upcoming 2023 AVAHO meeting in Chicago. Two items on the agenda particularly stand out: the role of artificial intelligence (AI) in oncology and the importance of cancer patient navigation. Dr Park acknowledges AI's potential to transform cancer diagnostics and drug discovery, particularly in aiding molecular profiling. Additionally, she highlights the value of cancer patient navigators in optimizing veteran care, particularly in the setting of geriatric oncology.

Soo Park, MD, discusses her expectations for the upcoming 2023 AVAHO meeting in Chicago. Two items on the agenda particularly stand out: the role of artificial intelligence (AI) in oncology and the importance of cancer patient navigation. Dr Park acknowledges AI's potential to transform cancer diagnostics and drug discovery, particularly in aiding molecular profiling. Additionally, she highlights the value of cancer patient navigators in optimizing veteran care, particularly in the setting of geriatric oncology.

Soo Park, MD, discusses her expectations for the upcoming 2023 AVAHO meeting in Chicago. Two items on the agenda particularly stand out: the role of artificial intelligence (AI) in oncology and the importance of cancer patient navigation. Dr Park acknowledges AI's potential to transform cancer diagnostics and drug discovery, particularly in aiding molecular profiling. Additionally, she highlights the value of cancer patient navigators in optimizing veteran care, particularly in the setting of geriatric oncology.

SINGAPORE – A few months after releasing its phase 1 and 2 data, OSE Immunotherapeutics, which is based in Nantes, France, has announced positive results for its therapeutic vaccine to treat cancer. Following its promising findings concerning early-stage melanoma, pancreatic cancer, ENT cancers, and HPV-associated anogenital cancer, the company-funded phase 3 Atalante-1 trial has shown the benefits of the Tedopi (OSE2101) vaccine in treating patients with advanced non–small cell lung cancer who are on their second or third line of treatment.

The results suggest that Tedopi is the most developmentally advanced therapeutic vaccine for cancer.

The data from Atalante-1 were presented at the World Conference on Lung Cancer and were simultaneously published in Annals of Oncology.

Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. In 95% of cases, tumors express at least one of these five antigens. The aim of integrating these five antigens is to prevent immune escape. The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients.
 

Study protocol

In the Atalante-1 trial, participants had locally advanced (unresectable and not eligible for radiotherapy) or metastatic (without alteration of the EGFR and ALK genes) non–small cell lung cancer that was resistant to previous immunotherapy. They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine.

In this trial, 219 patients were randomly assigned in a 2:1 ratio to receive the vaccine or standard-of-care chemotherapy (80% received docetaxel). The vaccine was administered subcutaneously on day 1 every 3 weeks for six cycles. After that point, the vaccine was administered every 8 weeks until 1 year of treatment and every 12 weeks thereafter. The primary endpoint was overall survival.
 

Secondary resistance

The plan was to enroll 363 patients in the protocol, but the study did not complete its recruitment phase because of the COVID-19 pandemic. As a result, the study was stopped after the enrollment of 219 patients.

“It didn’t have the power we would have liked, but it helped us understand that the people who benefited the most from the vaccine were patients who had responded to immunotherapy in the past. These patients have what is called ‘secondary resistance,’ ” explained Benjamin Besse, MD, PhD, during a press conference organized by OSE Immunotherapeutics. Dr. Besse, the study’s principal investigator, is the director of clinical research at Gustave Roussy, Villejuif, France.

Overall, the results weren’t significant. But the results were positive for patients who had previously responded well to immunotherapy for at least 3 months. Of the 219 patients, 118 (54%) had a positive response.

Among these patients with secondary resistance to immunotherapy, median OS was 11.1 months with Tedopi versus 7.5 months with docetaxel.

For these patients, the risk of death was reduced by 41% with the vaccine, compared with chemotherapy. Overall, 44% of patients lived for another year after receiving Tedopi, versus 27.5% with docetaxel.

“This study is a positive signal for overall survival in the selected population. In this study of 219 patients, we realized that just half of patients really benefited from the vaccine: those who had previously responded to immunotherapy,” said Dr. Besse. “The study needs confirmation from a further, larger phase 3 study in more than 300 patients with secondary resistance to immunotherapy to give us the statistical power we need to convince the regulatory authorities.”
 

Tolerability profile

Fewer serious adverse effects were reported with the vaccine than with chemotherapy (11.4% with Tedopi and 35.1% with docetaxel).

The vaccine also allowed patients to maintain a better quality of life. Scores from the Quality of Life Questionnaire Core 30, which explores several areas of daily life, were better with the vaccine. Change in patients’ overall well-being was delayed in the vaccine group: 3.3 months in the chemotherapy arm versus 9 months in the vaccine arm.

“The vaccine was well tolerated. It has benefits in terms of controlling disease symptoms and causes few side effects. Chemotherapy with docetaxel, meanwhile, is more toxic and may affect a patient’s overall well-being. It causes hair loss in practically 100% of patients, induces neuropathy, makes hands and feet swell, damages the nails, is associated with nausea and vomiting ...” noted Dr. Besse. He went on to say that after the trial, of the patients who stopped receiving the vaccine or chemotherapy (either for toxicity reasons or for disease progression), those who had been given the vaccine responded better to the subsequent chemotherapy “because their overall health was better.”
 

Clinical development

The clinical development of Tedopi is ongoing. Three trials are currently taking place. One study is comparing the Tedopi vaccine plus docetaxel with Tedopi plus nivolumab (immunotherapy not used as a first-line treatment) to determine whether the effects of these treatment combinations might might be enhanced for patients with previously treated lung cancer.

Another study relating to ovarian cancer is in the recruitment phase. The researchers seek to evaluate the vaccine alone or in combination with pembrolizumab for patients with platinum-sensitive ovarian cancer. Results from both trials are expected in 2025.

The third trial seeks to assess FOLFIRI as maintenance therapy or FOLFIRI as maintenance plus Tedopi for patients with pancreatic cancer to improve disease management. Efficacy data are expected next year.

OSE Immunotherapeutics is simultaneously working on a companion biomarker, the HLA-A2 test.

The study was funded by OSE Immunotherapeutics. Dr. Besse disclosed the following conflicts of interest (research funding, institution): AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Taiho Oncology, and Turning Point Therapeutics.

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

SINGAPORE – A few months after releasing its phase 1 and 2 data, OSE Immunotherapeutics, which is based in Nantes, France, has announced positive results for its therapeutic vaccine to treat cancer. Following its promising findings concerning early-stage melanoma, pancreatic cancer, ENT cancers, and HPV-associated anogenital cancer, the company-funded phase 3 Atalante-1 trial has shown the benefits of the Tedopi (OSE2101) vaccine in treating patients with advanced non–small cell lung cancer who are on their second or third line of treatment.

The results suggest that Tedopi is the most developmentally advanced therapeutic vaccine for cancer.

The data from Atalante-1 were presented at the World Conference on Lung Cancer and were simultaneously published in Annals of Oncology.

Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. In 95% of cases, tumors express at least one of these five antigens. The aim of integrating these five antigens is to prevent immune escape. The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients.
 

Study protocol

In the Atalante-1 trial, participants had locally advanced (unresectable and not eligible for radiotherapy) or metastatic (without alteration of the EGFR and ALK genes) non–small cell lung cancer that was resistant to previous immunotherapy. They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine.

In this trial, 219 patients were randomly assigned in a 2:1 ratio to receive the vaccine or standard-of-care chemotherapy (80% received docetaxel). The vaccine was administered subcutaneously on day 1 every 3 weeks for six cycles. After that point, the vaccine was administered every 8 weeks until 1 year of treatment and every 12 weeks thereafter. The primary endpoint was overall survival.
 

Secondary resistance

The plan was to enroll 363 patients in the protocol, but the study did not complete its recruitment phase because of the COVID-19 pandemic. As a result, the study was stopped after the enrollment of 219 patients.

“It didn’t have the power we would have liked, but it helped us understand that the people who benefited the most from the vaccine were patients who had responded to immunotherapy in the past. These patients have what is called ‘secondary resistance,’ ” explained Benjamin Besse, MD, PhD, during a press conference organized by OSE Immunotherapeutics. Dr. Besse, the study’s principal investigator, is the director of clinical research at Gustave Roussy, Villejuif, France.

Overall, the results weren’t significant. But the results were positive for patients who had previously responded well to immunotherapy for at least 3 months. Of the 219 patients, 118 (54%) had a positive response.

Among these patients with secondary resistance to immunotherapy, median OS was 11.1 months with Tedopi versus 7.5 months with docetaxel.

For these patients, the risk of death was reduced by 41% with the vaccine, compared with chemotherapy. Overall, 44% of patients lived for another year after receiving Tedopi, versus 27.5% with docetaxel.

“This study is a positive signal for overall survival in the selected population. In this study of 219 patients, we realized that just half of patients really benefited from the vaccine: those who had previously responded to immunotherapy,” said Dr. Besse. “The study needs confirmation from a further, larger phase 3 study in more than 300 patients with secondary resistance to immunotherapy to give us the statistical power we need to convince the regulatory authorities.”
 

Tolerability profile

Fewer serious adverse effects were reported with the vaccine than with chemotherapy (11.4% with Tedopi and 35.1% with docetaxel).

The vaccine also allowed patients to maintain a better quality of life. Scores from the Quality of Life Questionnaire Core 30, which explores several areas of daily life, were better with the vaccine. Change in patients’ overall well-being was delayed in the vaccine group: 3.3 months in the chemotherapy arm versus 9 months in the vaccine arm.

“The vaccine was well tolerated. It has benefits in terms of controlling disease symptoms and causes few side effects. Chemotherapy with docetaxel, meanwhile, is more toxic and may affect a patient’s overall well-being. It causes hair loss in practically 100% of patients, induces neuropathy, makes hands and feet swell, damages the nails, is associated with nausea and vomiting ...” noted Dr. Besse. He went on to say that after the trial, of the patients who stopped receiving the vaccine or chemotherapy (either for toxicity reasons or for disease progression), those who had been given the vaccine responded better to the subsequent chemotherapy “because their overall health was better.”
 

Clinical development

The clinical development of Tedopi is ongoing. Three trials are currently taking place. One study is comparing the Tedopi vaccine plus docetaxel with Tedopi plus nivolumab (immunotherapy not used as a first-line treatment) to determine whether the effects of these treatment combinations might might be enhanced for patients with previously treated lung cancer.

Another study relating to ovarian cancer is in the recruitment phase. The researchers seek to evaluate the vaccine alone or in combination with pembrolizumab for patients with platinum-sensitive ovarian cancer. Results from both trials are expected in 2025.

The third trial seeks to assess FOLFIRI as maintenance therapy or FOLFIRI as maintenance plus Tedopi for patients with pancreatic cancer to improve disease management. Efficacy data are expected next year.

OSE Immunotherapeutics is simultaneously working on a companion biomarker, the HLA-A2 test.

The study was funded by OSE Immunotherapeutics. Dr. Besse disclosed the following conflicts of interest (research funding, institution): AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Taiho Oncology, and Turning Point Therapeutics.

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

SINGAPORE – A few months after releasing its phase 1 and 2 data, OSE Immunotherapeutics, which is based in Nantes, France, has announced positive results for its therapeutic vaccine to treat cancer. Following its promising findings concerning early-stage melanoma, pancreatic cancer, ENT cancers, and HPV-associated anogenital cancer, the company-funded phase 3 Atalante-1 trial has shown the benefits of the Tedopi (OSE2101) vaccine in treating patients with advanced non–small cell lung cancer who are on their second or third line of treatment.

The results suggest that Tedopi is the most developmentally advanced therapeutic vaccine for cancer.

The data from Atalante-1 were presented at the World Conference on Lung Cancer and were simultaneously published in Annals of Oncology.

Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. In 95% of cases, tumors express at least one of these five antigens. The aim of integrating these five antigens is to prevent immune escape. The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients.
 

Study protocol

In the Atalante-1 trial, participants had locally advanced (unresectable and not eligible for radiotherapy) or metastatic (without alteration of the EGFR and ALK genes) non–small cell lung cancer that was resistant to previous immunotherapy. They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine.

In this trial, 219 patients were randomly assigned in a 2:1 ratio to receive the vaccine or standard-of-care chemotherapy (80% received docetaxel). The vaccine was administered subcutaneously on day 1 every 3 weeks for six cycles. After that point, the vaccine was administered every 8 weeks until 1 year of treatment and every 12 weeks thereafter. The primary endpoint was overall survival.
 

Secondary resistance

The plan was to enroll 363 patients in the protocol, but the study did not complete its recruitment phase because of the COVID-19 pandemic. As a result, the study was stopped after the enrollment of 219 patients.

“It didn’t have the power we would have liked, but it helped us understand that the people who benefited the most from the vaccine were patients who had responded to immunotherapy in the past. These patients have what is called ‘secondary resistance,’ ” explained Benjamin Besse, MD, PhD, during a press conference organized by OSE Immunotherapeutics. Dr. Besse, the study’s principal investigator, is the director of clinical research at Gustave Roussy, Villejuif, France.

Overall, the results weren’t significant. But the results were positive for patients who had previously responded well to immunotherapy for at least 3 months. Of the 219 patients, 118 (54%) had a positive response.

Among these patients with secondary resistance to immunotherapy, median OS was 11.1 months with Tedopi versus 7.5 months with docetaxel.

For these patients, the risk of death was reduced by 41% with the vaccine, compared with chemotherapy. Overall, 44% of patients lived for another year after receiving Tedopi, versus 27.5% with docetaxel.

“This study is a positive signal for overall survival in the selected population. In this study of 219 patients, we realized that just half of patients really benefited from the vaccine: those who had previously responded to immunotherapy,” said Dr. Besse. “The study needs confirmation from a further, larger phase 3 study in more than 300 patients with secondary resistance to immunotherapy to give us the statistical power we need to convince the regulatory authorities.”
 

Tolerability profile

Fewer serious adverse effects were reported with the vaccine than with chemotherapy (11.4% with Tedopi and 35.1% with docetaxel).

The vaccine also allowed patients to maintain a better quality of life. Scores from the Quality of Life Questionnaire Core 30, which explores several areas of daily life, were better with the vaccine. Change in patients’ overall well-being was delayed in the vaccine group: 3.3 months in the chemotherapy arm versus 9 months in the vaccine arm.

“The vaccine was well tolerated. It has benefits in terms of controlling disease symptoms and causes few side effects. Chemotherapy with docetaxel, meanwhile, is more toxic and may affect a patient’s overall well-being. It causes hair loss in practically 100% of patients, induces neuropathy, makes hands and feet swell, damages the nails, is associated with nausea and vomiting ...” noted Dr. Besse. He went on to say that after the trial, of the patients who stopped receiving the vaccine or chemotherapy (either for toxicity reasons or for disease progression), those who had been given the vaccine responded better to the subsequent chemotherapy “because their overall health was better.”
 

Clinical development

The clinical development of Tedopi is ongoing. Three trials are currently taking place. One study is comparing the Tedopi vaccine plus docetaxel with Tedopi plus nivolumab (immunotherapy not used as a first-line treatment) to determine whether the effects of these treatment combinations might might be enhanced for patients with previously treated lung cancer.

Another study relating to ovarian cancer is in the recruitment phase. The researchers seek to evaluate the vaccine alone or in combination with pembrolizumab for patients with platinum-sensitive ovarian cancer. Results from both trials are expected in 2025.

The third trial seeks to assess FOLFIRI as maintenance therapy or FOLFIRI as maintenance plus Tedopi for patients with pancreatic cancer to improve disease management. Efficacy data are expected next year.

OSE Immunotherapeutics is simultaneously working on a companion biomarker, the HLA-A2 test.

The study was funded by OSE Immunotherapeutics. Dr. Besse disclosed the following conflicts of interest (research funding, institution): AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Taiho Oncology, and Turning Point Therapeutics.

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

This transcript has been edited for clarity.

Hello. It’s Mark Kris from Memorial Sloan-Kettering, still musing on things I learned at ASCO 2023.

I learned that there is a new C word.

People used to be afraid to use the word “cancer,” so they would call it the C word. Hopefully we’ve gotten over that stigma, that cancer is an illness that can be fought like any other illness.

There’s a new C word now that people seem, again, afraid to use, and that word is “cure.” It’s almost a true rarity that – again, I’m talking about the lung cancer world in particular – folks use the word “cure.” I didn’t hear it at ASCO, but the truth of the matter is that’s a word we should be using and be using more.

What do our patients want? I think if you truly ask a patient what their goal of care should be, it would be to cure the illness. What I mean by “cure” is to eradicate the cancer that is in their body, keep the cancer and its effects from interfering with their ability to continue their lives, and to do it for the length of their natural life. That’s what our patients want. Yes, overall survival is important, but not as much as a life free of cancer and the burden that it puts on people having cancer in the body.

When you start thinking about cure and how to make it a goal of care, a number of issues immediately crop up. The first one is defining what is meant by “cure.” We don’t have a strict definition of cure. Again, I would probably go to the patients and ask them what they mean by it. There may be some landmark part of the definition that needs to be discussed and addressed, but again, to me it’s having your life not disturbed by cancer, and that generally comes by eradicating cancer. Living with cancer is harder than the living after cancer has been cured. But we don’t have a good definition.

We also don’t have a good way of designing clinical trials to assess whether the regimen is curative. I don’t think I’ve ever seen a trial in lung cancer that looked at the ability of any given treatment to cure patients. We need to come up with ways to design trials to do that. Now, in addition to clinical trials, we don’t have a good body of evidence to design our preclinical experiments to look for those treatments that can lead to cures, or total eradication of cancer in whatever model system might be used. If we make cure the goal, then we need to find ways preclinically to identify those strategies that could lead to that.

Also in the realm of clinical trials, we need a very clear statistical underpinning to show that one or another treatment has a better chance of cure and to show with scientific rigor that one treatment is better than the other when it comes to cure. I think there needs to be more attention to this, and as we think about revamping the clinical trial process, we need to focus more on cure.

I’m saving the most important step for last. None of this can happen unless we try to make it happen and we say cure is possible. My mentor, George Boswell, always taught us that we would, in every single patient with cancer, try to develop a curative strategy. Is there a curative strategy for this patient? If so, pursue it with all the tools and vigor that we have. We really need to think that way.

Obviously, not every patient with cancer can be cured with our current armamentarium of anticancer treatments, but we need to make sure we put it on the table. We need to [confirm] that a strategy does not currently exist that could lead to cure. And of course, if we do find that strategy, we need to pursue it with all the energy and resources that we have.

Please don’t be afraid to use the word “cure.” Our patients want that. They deserve it. We should work hard to try to provide it and work toward developing strategies that we can propose and cure more patients.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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

This transcript has been edited for clarity.

Hello. It’s Mark Kris from Memorial Sloan-Kettering, still musing on things I learned at ASCO 2023.

I learned that there is a new C word.

People used to be afraid to use the word “cancer,” so they would call it the C word. Hopefully we’ve gotten over that stigma, that cancer is an illness that can be fought like any other illness.

There’s a new C word now that people seem, again, afraid to use, and that word is “cure.” It’s almost a true rarity that – again, I’m talking about the lung cancer world in particular – folks use the word “cure.” I didn’t hear it at ASCO, but the truth of the matter is that’s a word we should be using and be using more.

What do our patients want? I think if you truly ask a patient what their goal of care should be, it would be to cure the illness. What I mean by “cure” is to eradicate the cancer that is in their body, keep the cancer and its effects from interfering with their ability to continue their lives, and to do it for the length of their natural life. That’s what our patients want. Yes, overall survival is important, but not as much as a life free of cancer and the burden that it puts on people having cancer in the body.

When you start thinking about cure and how to make it a goal of care, a number of issues immediately crop up. The first one is defining what is meant by “cure.” We don’t have a strict definition of cure. Again, I would probably go to the patients and ask them what they mean by it. There may be some landmark part of the definition that needs to be discussed and addressed, but again, to me it’s having your life not disturbed by cancer, and that generally comes by eradicating cancer. Living with cancer is harder than the living after cancer has been cured. But we don’t have a good definition.

We also don’t have a good way of designing clinical trials to assess whether the regimen is curative. I don’t think I’ve ever seen a trial in lung cancer that looked at the ability of any given treatment to cure patients. We need to come up with ways to design trials to do that. Now, in addition to clinical trials, we don’t have a good body of evidence to design our preclinical experiments to look for those treatments that can lead to cures, or total eradication of cancer in whatever model system might be used. If we make cure the goal, then we need to find ways preclinically to identify those strategies that could lead to that.

Also in the realm of clinical trials, we need a very clear statistical underpinning to show that one or another treatment has a better chance of cure and to show with scientific rigor that one treatment is better than the other when it comes to cure. I think there needs to be more attention to this, and as we think about revamping the clinical trial process, we need to focus more on cure.

I’m saving the most important step for last. None of this can happen unless we try to make it happen and we say cure is possible. My mentor, George Boswell, always taught us that we would, in every single patient with cancer, try to develop a curative strategy. Is there a curative strategy for this patient? If so, pursue it with all the tools and vigor that we have. We really need to think that way.

Obviously, not every patient with cancer can be cured with our current armamentarium of anticancer treatments, but we need to make sure we put it on the table. We need to [confirm] that a strategy does not currently exist that could lead to cure. And of course, if we do find that strategy, we need to pursue it with all the energy and resources that we have.

Please don’t be afraid to use the word “cure.” Our patients want that. They deserve it. We should work hard to try to provide it and work toward developing strategies that we can propose and cure more patients.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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

This transcript has been edited for clarity.

Hello. It’s Mark Kris from Memorial Sloan-Kettering, still musing on things I learned at ASCO 2023.

I learned that there is a new C word.

People used to be afraid to use the word “cancer,” so they would call it the C word. Hopefully we’ve gotten over that stigma, that cancer is an illness that can be fought like any other illness.

There’s a new C word now that people seem, again, afraid to use, and that word is “cure.” It’s almost a true rarity that – again, I’m talking about the lung cancer world in particular – folks use the word “cure.” I didn’t hear it at ASCO, but the truth of the matter is that’s a word we should be using and be using more.

What do our patients want? I think if you truly ask a patient what their goal of care should be, it would be to cure the illness. What I mean by “cure” is to eradicate the cancer that is in their body, keep the cancer and its effects from interfering with their ability to continue their lives, and to do it for the length of their natural life. That’s what our patients want. Yes, overall survival is important, but not as much as a life free of cancer and the burden that it puts on people having cancer in the body.

When you start thinking about cure and how to make it a goal of care, a number of issues immediately crop up. The first one is defining what is meant by “cure.” We don’t have a strict definition of cure. Again, I would probably go to the patients and ask them what they mean by it. There may be some landmark part of the definition that needs to be discussed and addressed, but again, to me it’s having your life not disturbed by cancer, and that generally comes by eradicating cancer. Living with cancer is harder than the living after cancer has been cured. But we don’t have a good definition.

We also don’t have a good way of designing clinical trials to assess whether the regimen is curative. I don’t think I’ve ever seen a trial in lung cancer that looked at the ability of any given treatment to cure patients. We need to come up with ways to design trials to do that. Now, in addition to clinical trials, we don’t have a good body of evidence to design our preclinical experiments to look for those treatments that can lead to cures, or total eradication of cancer in whatever model system might be used. If we make cure the goal, then we need to find ways preclinically to identify those strategies that could lead to that.

Also in the realm of clinical trials, we need a very clear statistical underpinning to show that one or another treatment has a better chance of cure and to show with scientific rigor that one treatment is better than the other when it comes to cure. I think there needs to be more attention to this, and as we think about revamping the clinical trial process, we need to focus more on cure.

I’m saving the most important step for last. None of this can happen unless we try to make it happen and we say cure is possible. My mentor, George Boswell, always taught us that we would, in every single patient with cancer, try to develop a curative strategy. Is there a curative strategy for this patient? If so, pursue it with all the tools and vigor that we have. We really need to think that way.

Obviously, not every patient with cancer can be cured with our current armamentarium of anticancer treatments, but we need to make sure we put it on the table. We need to [confirm] that a strategy does not currently exist that could lead to cure. And of course, if we do find that strategy, we need to pursue it with all the energy and resources that we have.

Please don’t be afraid to use the word “cure.” Our patients want that. They deserve it. We should work hard to try to provide it and work toward developing strategies that we can propose and cure more patients.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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