The number of doctors of osteopathic medicine (DOs) is enjoying a significant growth pattern. This year alone, 7,300 osteopathic physicians are entering the workforce, and they make up more than 25% of the medical student population. The pipeline of future DOs is at an all-time high of 36,500 students, according to the American Osteopathic Association.

All 50 states plus Washington, D.C., have DO practices, and Florida ranks third in terms of states with the most practicing DOs, topped by California in the No. 1 spot and Pennsylvania in second. New York and Michigan round out the top 5.

The pipeline to the profession is in a growth mode, too. For the upcoming academic year, the AOA’s Commission on Osteopathic College Accreditation will accredit 38 colleges of osteopathic medicine in about 60 different locations.

Although DOs have existed for more than 100 years, historically they have sat somewhat in the shadow of their MD peers. That tide has turned, for a variety of reasons – one of which is recognition via several high-profile DOs. Look no further than the White House, for instance, where President Biden’s physician is Kevin O’Connor, DO – the second DO to hold the position.

“The misrepresentation of osteopathic physicians has been a recent issue outside the nation’s health care delivery system,” says the American Medical Association’s Robert Mills. “To combat this mischaracterization, the AMA and the AOA issued a joint statement [in 2020] highlighting the fact that DOs are licensed physicians who practice in every specialty area and have equivalent training and practice rights to their MD peers.”
 

Attraction to the DO philosophy

For many DOs, the path to osteopathic medicine was always a clear one. “I wanted to go into osteopathic medicine from the age of 17,” says Nehal Gheewala, DO, national director of growth at ChenMed, a national primary care medical center.

Dr. Gheewala, who graduated from medical school in 2014, says he first spent time learning about the DO’s holistic philosophy, which appealed to him. “I liked how they were invested in their patient’s care, and that they first tried to treat musculoskeletal pain with manipulation. The result were quick, sometimes on the spot.”

While in medical school, Dr. Gheewala was joined by 250 peers seeking a DO rather than an MD. “I never felt like I was in the minority,” he says, “and today, as a practicing physician in Florida, we have a good number of DOs.”

Like Dr. Gheewala, Samuel Werner, a New Jersey–based DO, was inspired by his father, a DO who has served as a small-town general practitioner. “Growing up, I saw how well-respected my dad was in the community and watched his connection with patients,” Dr. Werner says. “He had the ability to pick up on small details others didn’t.”

Today, Dr. Werner sees the recognition and respect of DOs growing beyond where it was several decades ago.

One factor that is helping raise the DO profile is that residencies fall under the same umbrella for matching. In most states, medical licensing is the same, as well. Choosing to pursue a DO career requires additional training in wellness and manipulation. “In every specialty of medicine, DO students train alongside MD students,” Dr. Werner says. “In practice, most patients are unaware if they’re treated by a DO or an MD.”

That has sometimes been Dr. Gheewala’s experience. “Plenty of patients don’t ask whether I’m an MD or a DO,” he says, “and it doesn’t matter. We’re all board-certified doctors and as long as we’re taking care of, and spending time with, our patients, that’s what they want.”

Joseph A. Giaimo, a DO in Florida who has practiced for more than 30 years and is a past president of the AOA, says that some patients will seek out a DO instead of an MD. “Many patients see me because they specifically want to work with a DO; many of them are snowbirds who come to Florida during the winter,” he explains.

In his long career as a DO, Dr. Giaimo has witnessed the profession’s growth alongside a fading stigma that it’s somehow less “authentic” than allopathic medicine. “There are still people who need to be educated on osteopathic medicine, but much of that has simply been a lack of understanding,” he says. “That’s changing, and it’s our role to continue to educate people on what we’re about.”

Dr. Giaimo says that osteopathic medicine is striking the right tone in the moment, which is helpful to recognition and growth. “Coming out of the pandemic, people are more focused on staying healthy, and osteopathy offers an appealing approach,” he says. “There’s no better time for the two houses of medicine to come together, and it’s a great time to be in osteopathy.”
 

Moving forward

One of the biggest places the physician shortage is problematic is in rural America. The federal government estimates that by 2025, there will be a physician shortage of 25,000 primary care doctors in these areas. This is another way in which the growing osteopathic field is having an impact.

“We have a number of schools in underserved areas, such as Oklahoma and on indigenous lands,” says Dr. Giaimo. “There is a concerted effort to reach these communities, and we’re getting some recognition for those efforts, too.”

Dr. Gheewala also sees a greater emphasis on primary care physicians today, something that he believes has led more people to explore becoming or seeing a DO instead of an MD.

A full 57% of DOs focus on primary care, such as family practice, pediatrics, and internal medicine, with the others in specialized care. If those focused on primary care can fill some of the physician shortages, Dr. Gheewala says, it can help keep patients out of hospitals for their first line of care, reducing health care costs.

The tides are turning in the medical profession, as well, when it comes to respecting the osteopathy field. Students who graduate from osteopathic programs also have a high acceptance rate into residencies, which Dr. Giaimo credits to several factors.

He also doesn’t discount the fact that DOs are talking more about their practice approaches these days. “It hits the right note for modern medicine, and it’s also what the consumer is looking for today,” he adds.
 

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

The number of doctors of osteopathic medicine (DOs) is enjoying a significant growth pattern. This year alone, 7,300 osteopathic physicians are entering the workforce, and they make up more than 25% of the medical student population. The pipeline of future DOs is at an all-time high of 36,500 students, according to the American Osteopathic Association.

All 50 states plus Washington, D.C., have DO practices, and Florida ranks third in terms of states with the most practicing DOs, topped by California in the No. 1 spot and Pennsylvania in second. New York and Michigan round out the top 5.

The pipeline to the profession is in a growth mode, too. For the upcoming academic year, the AOA’s Commission on Osteopathic College Accreditation will accredit 38 colleges of osteopathic medicine in about 60 different locations.

Although DOs have existed for more than 100 years, historically they have sat somewhat in the shadow of their MD peers. That tide has turned, for a variety of reasons – one of which is recognition via several high-profile DOs. Look no further than the White House, for instance, where President Biden’s physician is Kevin O’Connor, DO – the second DO to hold the position.

“The misrepresentation of osteopathic physicians has been a recent issue outside the nation’s health care delivery system,” says the American Medical Association’s Robert Mills. “To combat this mischaracterization, the AMA and the AOA issued a joint statement [in 2020] highlighting the fact that DOs are licensed physicians who practice in every specialty area and have equivalent training and practice rights to their MD peers.”
 

Attraction to the DO philosophy

For many DOs, the path to osteopathic medicine was always a clear one. “I wanted to go into osteopathic medicine from the age of 17,” says Nehal Gheewala, DO, national director of growth at ChenMed, a national primary care medical center.

Dr. Gheewala, who graduated from medical school in 2014, says he first spent time learning about the DO’s holistic philosophy, which appealed to him. “I liked how they were invested in their patient’s care, and that they first tried to treat musculoskeletal pain with manipulation. The result were quick, sometimes on the spot.”

While in medical school, Dr. Gheewala was joined by 250 peers seeking a DO rather than an MD. “I never felt like I was in the minority,” he says, “and today, as a practicing physician in Florida, we have a good number of DOs.”

Like Dr. Gheewala, Samuel Werner, a New Jersey–based DO, was inspired by his father, a DO who has served as a small-town general practitioner. “Growing up, I saw how well-respected my dad was in the community and watched his connection with patients,” Dr. Werner says. “He had the ability to pick up on small details others didn’t.”

Today, Dr. Werner sees the recognition and respect of DOs growing beyond where it was several decades ago.

One factor that is helping raise the DO profile is that residencies fall under the same umbrella for matching. In most states, medical licensing is the same, as well. Choosing to pursue a DO career requires additional training in wellness and manipulation. “In every specialty of medicine, DO students train alongside MD students,” Dr. Werner says. “In practice, most patients are unaware if they’re treated by a DO or an MD.”

That has sometimes been Dr. Gheewala’s experience. “Plenty of patients don’t ask whether I’m an MD or a DO,” he says, “and it doesn’t matter. We’re all board-certified doctors and as long as we’re taking care of, and spending time with, our patients, that’s what they want.”

Joseph A. Giaimo, a DO in Florida who has practiced for more than 30 years and is a past president of the AOA, says that some patients will seek out a DO instead of an MD. “Many patients see me because they specifically want to work with a DO; many of them are snowbirds who come to Florida during the winter,” he explains.

In his long career as a DO, Dr. Giaimo has witnessed the profession’s growth alongside a fading stigma that it’s somehow less “authentic” than allopathic medicine. “There are still people who need to be educated on osteopathic medicine, but much of that has simply been a lack of understanding,” he says. “That’s changing, and it’s our role to continue to educate people on what we’re about.”

Dr. Giaimo says that osteopathic medicine is striking the right tone in the moment, which is helpful to recognition and growth. “Coming out of the pandemic, people are more focused on staying healthy, and osteopathy offers an appealing approach,” he says. “There’s no better time for the two houses of medicine to come together, and it’s a great time to be in osteopathy.”
 

Moving forward

One of the biggest places the physician shortage is problematic is in rural America. The federal government estimates that by 2025, there will be a physician shortage of 25,000 primary care doctors in these areas. This is another way in which the growing osteopathic field is having an impact.

“We have a number of schools in underserved areas, such as Oklahoma and on indigenous lands,” says Dr. Giaimo. “There is a concerted effort to reach these communities, and we’re getting some recognition for those efforts, too.”

Dr. Gheewala also sees a greater emphasis on primary care physicians today, something that he believes has led more people to explore becoming or seeing a DO instead of an MD.

A full 57% of DOs focus on primary care, such as family practice, pediatrics, and internal medicine, with the others in specialized care. If those focused on primary care can fill some of the physician shortages, Dr. Gheewala says, it can help keep patients out of hospitals for their first line of care, reducing health care costs.

The tides are turning in the medical profession, as well, when it comes to respecting the osteopathy field. Students who graduate from osteopathic programs also have a high acceptance rate into residencies, which Dr. Giaimo credits to several factors.

He also doesn’t discount the fact that DOs are talking more about their practice approaches these days. “It hits the right note for modern medicine, and it’s also what the consumer is looking for today,” he adds.
 

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

The number of doctors of osteopathic medicine (DOs) is enjoying a significant growth pattern. This year alone, 7,300 osteopathic physicians are entering the workforce, and they make up more than 25% of the medical student population. The pipeline of future DOs is at an all-time high of 36,500 students, according to the American Osteopathic Association.

All 50 states plus Washington, D.C., have DO practices, and Florida ranks third in terms of states with the most practicing DOs, topped by California in the No. 1 spot and Pennsylvania in second. New York and Michigan round out the top 5.

The pipeline to the profession is in a growth mode, too. For the upcoming academic year, the AOA’s Commission on Osteopathic College Accreditation will accredit 38 colleges of osteopathic medicine in about 60 different locations.

Although DOs have existed for more than 100 years, historically they have sat somewhat in the shadow of their MD peers. That tide has turned, for a variety of reasons – one of which is recognition via several high-profile DOs. Look no further than the White House, for instance, where President Biden’s physician is Kevin O’Connor, DO – the second DO to hold the position.

“The misrepresentation of osteopathic physicians has been a recent issue outside the nation’s health care delivery system,” says the American Medical Association’s Robert Mills. “To combat this mischaracterization, the AMA and the AOA issued a joint statement [in 2020] highlighting the fact that DOs are licensed physicians who practice in every specialty area and have equivalent training and practice rights to their MD peers.”
 

Attraction to the DO philosophy

For many DOs, the path to osteopathic medicine was always a clear one. “I wanted to go into osteopathic medicine from the age of 17,” says Nehal Gheewala, DO, national director of growth at ChenMed, a national primary care medical center.

Dr. Gheewala, who graduated from medical school in 2014, says he first spent time learning about the DO’s holistic philosophy, which appealed to him. “I liked how they were invested in their patient’s care, and that they first tried to treat musculoskeletal pain with manipulation. The result were quick, sometimes on the spot.”

While in medical school, Dr. Gheewala was joined by 250 peers seeking a DO rather than an MD. “I never felt like I was in the minority,” he says, “and today, as a practicing physician in Florida, we have a good number of DOs.”

Like Dr. Gheewala, Samuel Werner, a New Jersey–based DO, was inspired by his father, a DO who has served as a small-town general practitioner. “Growing up, I saw how well-respected my dad was in the community and watched his connection with patients,” Dr. Werner says. “He had the ability to pick up on small details others didn’t.”

Today, Dr. Werner sees the recognition and respect of DOs growing beyond where it was several decades ago.

One factor that is helping raise the DO profile is that residencies fall under the same umbrella for matching. In most states, medical licensing is the same, as well. Choosing to pursue a DO career requires additional training in wellness and manipulation. “In every specialty of medicine, DO students train alongside MD students,” Dr. Werner says. “In practice, most patients are unaware if they’re treated by a DO or an MD.”

That has sometimes been Dr. Gheewala’s experience. “Plenty of patients don’t ask whether I’m an MD or a DO,” he says, “and it doesn’t matter. We’re all board-certified doctors and as long as we’re taking care of, and spending time with, our patients, that’s what they want.”

Joseph A. Giaimo, a DO in Florida who has practiced for more than 30 years and is a past president of the AOA, says that some patients will seek out a DO instead of an MD. “Many patients see me because they specifically want to work with a DO; many of them are snowbirds who come to Florida during the winter,” he explains.

In his long career as a DO, Dr. Giaimo has witnessed the profession’s growth alongside a fading stigma that it’s somehow less “authentic” than allopathic medicine. “There are still people who need to be educated on osteopathic medicine, but much of that has simply been a lack of understanding,” he says. “That’s changing, and it’s our role to continue to educate people on what we’re about.”

Dr. Giaimo says that osteopathic medicine is striking the right tone in the moment, which is helpful to recognition and growth. “Coming out of the pandemic, people are more focused on staying healthy, and osteopathy offers an appealing approach,” he says. “There’s no better time for the two houses of medicine to come together, and it’s a great time to be in osteopathy.”
 

Moving forward

One of the biggest places the physician shortage is problematic is in rural America. The federal government estimates that by 2025, there will be a physician shortage of 25,000 primary care doctors in these areas. This is another way in which the growing osteopathic field is having an impact.

“We have a number of schools in underserved areas, such as Oklahoma and on indigenous lands,” says Dr. Giaimo. “There is a concerted effort to reach these communities, and we’re getting some recognition for those efforts, too.”

Dr. Gheewala also sees a greater emphasis on primary care physicians today, something that he believes has led more people to explore becoming or seeing a DO instead of an MD.

A full 57% of DOs focus on primary care, such as family practice, pediatrics, and internal medicine, with the others in specialized care. If those focused on primary care can fill some of the physician shortages, Dr. Gheewala says, it can help keep patients out of hospitals for their first line of care, reducing health care costs.

The tides are turning in the medical profession, as well, when it comes to respecting the osteopathy field. Students who graduate from osteopathic programs also have a high acceptance rate into residencies, which Dr. Giaimo credits to several factors.

He also doesn’t discount the fact that DOs are talking more about their practice approaches these days. “It hits the right note for modern medicine, and it’s also what the consumer is looking for today,” he adds.
 

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

Research that could set the stage for future clinical trials explored the potential role of adenosine signaling in altering the immune microenvironment of colorectal cancer (CRC), according to a study appearing in Cellular and Molecular Gastroenterology and Hepatology.

The study in human-derived cells and CRC mouse models suggests that addition of a CD73 inhibitor to the CDK4/6 inhibitor palbociclib may hold promise in the treatment of CRC because CD73 can produce extracellular adenosine. The results hold promise for future research since anticancer therapies often prompt increased expression of PD-L1, and CDK4/6 inhibitor monotherapy can fail because of accumulation of PD-L1 after such treatment.

Previous research has suggested that extracellular adenosine-mediated signaling can lead to accumulation of tumor-associated macrophages (TAMs) and an immunosuppressive tumor microenvironment. TAMs play an important role in the intestinal mucosal immune system in CRC, which mediates tumor-promoting metabolites in the intestine and inflammatory pathways that can lead to and progress CRC. TAMs are also linked to increases in extracellular enzymes like CD39 and CD73 as well as resistance to chemotherapy and anti-PD-1/PD-L1 therapy in CRC. Furthermore, they express PD-L1 and they promote other immunosuppressive molecules.

In normal tissues, CD73 produces adenosine to tamp down excessive immune responses. Some tumors express CD73 or even induce expression in normal cells, leading to immunosuppression in the tumor microenvironment. Previous studies have shown that CD73 expression is a biomarker for poor outcomes in gastric, liver, pancreatic, and colorectal cancer, the authors of this study noted.

To better understand the impact of adenosine, the researchers exposed human macrophages derived from peripheral blood to adenosine, and then analyzed the results using flow cytometry and Western blot. They used RNA sequencing and proteomics to discern changes in the cells that resulted from the exposure.

Adenosine treatment led to changes in the expression levels of genes involved in the cell cycle, cell division, cell cycle phase transition, and DNA repair. The researchers emphasized that extracellular treatment with adenosine led to a reduction in expression of the cell cycle–related gene CCND1, which encodes cyclin D1. Among three genes in the cyclin D family tested, CCND1 was the only one affected by adenosine. Cyclin D1 protein levels also went down.

Cyclin D1 is a known actor in regulating the cell cycle and tumorigenesis, among other roles. Previous reports indicated that cyclin D1 participates in posttranslational regulation of PD-L1, and the current study suggests it plays a similar role in TAMs after exposure to adenosine in the tumor microenvironment. Myeloid cells high in cyclin D1 expression had low levels or even an absence of the immunosuppressive molecule CD39. “Taken together, cyclin D1 may be one of the major orchestrators that trigger the differentiation of pro-tumorigenic TAMs. Our findings suggest a novel immune checkpoint regulatory mechanism of extracellular adenosine signaling, which might be related to the cell cycle of macrophages,” the authors wrote.

The researchers then introduced a short hairpin RNA directed against CCND1. This led to increases in PD-L1 protein levels. Simultaneous treatment with adenosine led to a slight increase in levels of the PD-L1 protein, which suggests that reduction of CCND1 levels is the primary cause of increased PD-L1, according to the authors.

The CD73 inhibitor AB680, currently in phase 1 clinical trials for castration-resistant prostate cancer and advanced pancreatic cancer and developed by Arcus Biosciences, led to reduced PD-L1 levels in both human and mouse macrophages, and AB680 combined with the CDK4/6 inhibitor palbociclib led to greater inhibition of tumor growth than palbociclib alone in CRC mouse models.

“Thus, the promising effects of CD73 inhibitors might breathe new life for those old drugs and provide potent therapeutic strategies. Given that the therapeutic effects of PD-1/PD-L1 immunotherapy have not been conclusively demonstrated in patients with CRC, our observations should support clinical trials of new combinational therapies for CRC,” the authors wrote.

The authors disclose no conflicts.
 

Research that could set the stage for future clinical trials explored the potential role of adenosine signaling in altering the immune microenvironment of colorectal cancer (CRC), according to a study appearing in Cellular and Molecular Gastroenterology and Hepatology.

The study in human-derived cells and CRC mouse models suggests that addition of a CD73 inhibitor to the CDK4/6 inhibitor palbociclib may hold promise in the treatment of CRC because CD73 can produce extracellular adenosine. The results hold promise for future research since anticancer therapies often prompt increased expression of PD-L1, and CDK4/6 inhibitor monotherapy can fail because of accumulation of PD-L1 after such treatment.

Previous research has suggested that extracellular adenosine-mediated signaling can lead to accumulation of tumor-associated macrophages (TAMs) and an immunosuppressive tumor microenvironment. TAMs play an important role in the intestinal mucosal immune system in CRC, which mediates tumor-promoting metabolites in the intestine and inflammatory pathways that can lead to and progress CRC. TAMs are also linked to increases in extracellular enzymes like CD39 and CD73 as well as resistance to chemotherapy and anti-PD-1/PD-L1 therapy in CRC. Furthermore, they express PD-L1 and they promote other immunosuppressive molecules.

In normal tissues, CD73 produces adenosine to tamp down excessive immune responses. Some tumors express CD73 or even induce expression in normal cells, leading to immunosuppression in the tumor microenvironment. Previous studies have shown that CD73 expression is a biomarker for poor outcomes in gastric, liver, pancreatic, and colorectal cancer, the authors of this study noted.

To better understand the impact of adenosine, the researchers exposed human macrophages derived from peripheral blood to adenosine, and then analyzed the results using flow cytometry and Western blot. They used RNA sequencing and proteomics to discern changes in the cells that resulted from the exposure.

Adenosine treatment led to changes in the expression levels of genes involved in the cell cycle, cell division, cell cycle phase transition, and DNA repair. The researchers emphasized that extracellular treatment with adenosine led to a reduction in expression of the cell cycle–related gene CCND1, which encodes cyclin D1. Among three genes in the cyclin D family tested, CCND1 was the only one affected by adenosine. Cyclin D1 protein levels also went down.

Cyclin D1 is a known actor in regulating the cell cycle and tumorigenesis, among other roles. Previous reports indicated that cyclin D1 participates in posttranslational regulation of PD-L1, and the current study suggests it plays a similar role in TAMs after exposure to adenosine in the tumor microenvironment. Myeloid cells high in cyclin D1 expression had low levels or even an absence of the immunosuppressive molecule CD39. “Taken together, cyclin D1 may be one of the major orchestrators that trigger the differentiation of pro-tumorigenic TAMs. Our findings suggest a novel immune checkpoint regulatory mechanism of extracellular adenosine signaling, which might be related to the cell cycle of macrophages,” the authors wrote.

The researchers then introduced a short hairpin RNA directed against CCND1. This led to increases in PD-L1 protein levels. Simultaneous treatment with adenosine led to a slight increase in levels of the PD-L1 protein, which suggests that reduction of CCND1 levels is the primary cause of increased PD-L1, according to the authors.

The CD73 inhibitor AB680, currently in phase 1 clinical trials for castration-resistant prostate cancer and advanced pancreatic cancer and developed by Arcus Biosciences, led to reduced PD-L1 levels in both human and mouse macrophages, and AB680 combined with the CDK4/6 inhibitor palbociclib led to greater inhibition of tumor growth than palbociclib alone in CRC mouse models.

“Thus, the promising effects of CD73 inhibitors might breathe new life for those old drugs and provide potent therapeutic strategies. Given that the therapeutic effects of PD-1/PD-L1 immunotherapy have not been conclusively demonstrated in patients with CRC, our observations should support clinical trials of new combinational therapies for CRC,” the authors wrote.

The authors disclose no conflicts.
 

Research that could set the stage for future clinical trials explored the potential role of adenosine signaling in altering the immune microenvironment of colorectal cancer (CRC), according to a study appearing in Cellular and Molecular Gastroenterology and Hepatology.

The study in human-derived cells and CRC mouse models suggests that addition of a CD73 inhibitor to the CDK4/6 inhibitor palbociclib may hold promise in the treatment of CRC because CD73 can produce extracellular adenosine. The results hold promise for future research since anticancer therapies often prompt increased expression of PD-L1, and CDK4/6 inhibitor monotherapy can fail because of accumulation of PD-L1 after such treatment.

Previous research has suggested that extracellular adenosine-mediated signaling can lead to accumulation of tumor-associated macrophages (TAMs) and an immunosuppressive tumor microenvironment. TAMs play an important role in the intestinal mucosal immune system in CRC, which mediates tumor-promoting metabolites in the intestine and inflammatory pathways that can lead to and progress CRC. TAMs are also linked to increases in extracellular enzymes like CD39 and CD73 as well as resistance to chemotherapy and anti-PD-1/PD-L1 therapy in CRC. Furthermore, they express PD-L1 and they promote other immunosuppressive molecules.

In normal tissues, CD73 produces adenosine to tamp down excessive immune responses. Some tumors express CD73 or even induce expression in normal cells, leading to immunosuppression in the tumor microenvironment. Previous studies have shown that CD73 expression is a biomarker for poor outcomes in gastric, liver, pancreatic, and colorectal cancer, the authors of this study noted.

To better understand the impact of adenosine, the researchers exposed human macrophages derived from peripheral blood to adenosine, and then analyzed the results using flow cytometry and Western blot. They used RNA sequencing and proteomics to discern changes in the cells that resulted from the exposure.

Adenosine treatment led to changes in the expression levels of genes involved in the cell cycle, cell division, cell cycle phase transition, and DNA repair. The researchers emphasized that extracellular treatment with adenosine led to a reduction in expression of the cell cycle–related gene CCND1, which encodes cyclin D1. Among three genes in the cyclin D family tested, CCND1 was the only one affected by adenosine. Cyclin D1 protein levels also went down.

Cyclin D1 is a known actor in regulating the cell cycle and tumorigenesis, among other roles. Previous reports indicated that cyclin D1 participates in posttranslational regulation of PD-L1, and the current study suggests it plays a similar role in TAMs after exposure to adenosine in the tumor microenvironment. Myeloid cells high in cyclin D1 expression had low levels or even an absence of the immunosuppressive molecule CD39. “Taken together, cyclin D1 may be one of the major orchestrators that trigger the differentiation of pro-tumorigenic TAMs. Our findings suggest a novel immune checkpoint regulatory mechanism of extracellular adenosine signaling, which might be related to the cell cycle of macrophages,” the authors wrote.

The researchers then introduced a short hairpin RNA directed against CCND1. This led to increases in PD-L1 protein levels. Simultaneous treatment with adenosine led to a slight increase in levels of the PD-L1 protein, which suggests that reduction of CCND1 levels is the primary cause of increased PD-L1, according to the authors.

The CD73 inhibitor AB680, currently in phase 1 clinical trials for castration-resistant prostate cancer and advanced pancreatic cancer and developed by Arcus Biosciences, led to reduced PD-L1 levels in both human and mouse macrophages, and AB680 combined with the CDK4/6 inhibitor palbociclib led to greater inhibition of tumor growth than palbociclib alone in CRC mouse models.

“Thus, the promising effects of CD73 inhibitors might breathe new life for those old drugs and provide potent therapeutic strategies. Given that the therapeutic effects of PD-1/PD-L1 immunotherapy have not been conclusively demonstrated in patients with CRC, our observations should support clinical trials of new combinational therapies for CRC,” the authors wrote.

The authors disclose no conflicts.
 

The RNA interference (RNAi) therapeutic, patisiran (Onpattro, Alnylam), showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test (6-MWT), compared with placebo, in the treatment of transthyretin-mediated amyloidosis with cardiomyopathy, in the APOLLO-B trial.

The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.

These positive results, their first formal presentation, were announced Sept. 8 at the 18th International Symposium on Amyloidosis. However, the company announced positive top-line results from the trial in early August.

Transthyretin-mediated (ATTR) amyloidosis is a rare, rapidly progressive, debilitating disease caused by misfolded transthyretin (TTR) proteins which accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal tract.

There are two different types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis, caused by a TTR gene variant, and wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant. hATTR amyloidosis affects approximately 50,000 people worldwide, whereas wtATTR amyloidosis is estimated to affect 200,000-300,000 people worldwide.

Patisiran is an intravenously administered RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. It is also approved in the European Union, Switzerland, Brazil, and Japan for a similar indication. It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues.

“The results of the APOLLO-B phase 3 study are impressive, as I believe they underscore the potential for patisiran to provide a benefit on functional capacity and quality of life in patients living with ATTR amyloidosis with cardiomyopathy. Furthermore, these results were seen after only 12 months of treatment,” Mathew Maurer, MD, Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical Center, New York, said in an Alnylam press release.

“The cardiac manifestations associated with ATTR amyloidosis can have a devastating impact on patients’ lives and current treatment options are limited. With the rapidly progressive nature of the disease, there is a significant need for treatments like patisiran, which has the potential to be a new option for patients and physicians to treat the cardiomyopathy of ATTR amyloidosis,” Dr. Maurer added.

APOLLO-B is a phase 3, randomized, double-blind study evaluating the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The study enrolled 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy who were randomly assigned 1:1 to receive 0.3 mg/kg of patisiran or placebo intravenously administered every 3 weeks over a 12-month treatment period. After 12 months, all patients will receive patisiran in an open-label extension.

Results at 12 months, reported by Alnylam, found that the primary endpoint, the 6-MWT, showed a median change from baseline of –8.15 m for the patisiran group and –21.34 m for the placebo group, a significant difference favoring patisiran.

The first secondary endpoint was health status and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary score. This showed a mean change from baseline of +0.300 for the patisiran group and –3.408 for the placebo group, a significant difference favoring patisiran.

Secondary composite outcome endpoints did not achieve statistical significance.

A nonsignificant result (win ratio, 1.27; P = .0574) was found on the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months, compared with placebo.

The final two composite endpoints were not powered for statistical significance, given the sample size and short duration of the study – all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in patients not on tafamidis at baseline (hazard ratio, 0.997) and in the overall study population (HR, 0.883).

Patisiran achieved a rapid and sustained reduction in serum TTR levels, with a mean percent reduction from baseline in serum TTR reduction of 87% at month 12.

A beneficial effect on the exploratory endpoint, N-terminal of the prohormone brain natriuretic peptide, a measure of cardiac stress, was observed in the patisiran arm, with a 20% reduction in the adjusted geometric mean fold change from baseline, compared with placebo.

Patisiran also demonstrated an encouraging safety and tolerability profile, including no cardiac safety concerns relative to placebo, during the 12-month treatment period, Alnylam reported.

The majority of adverse events were mild or moderate in severity. Treatment emergent adverse events in the patisiran group included infusion-related reactions, arthralgia, and muscle spasms.

In the safety analysis, there were five deaths (2.8%) observed in patisiran-treated patients and eight deaths (4.5%) observed in the placebo group.

Pushkal Garg, MD, chief medical officer at Alnylam, said: “We believe these data validate the therapeutic hypothesis that TTR silencing by an RNAi therapeutic may be an effective approach to treating cardiomyopathy of both wild-type and hereditary ATTR amyloidosis.”

Alnylam plans to file a supplemental new drug application for patisiran as a potential treatment for ATTR amyloidosis with cardiomyopathy in the United States in late 2022.

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

The RNA interference (RNAi) therapeutic, patisiran (Onpattro, Alnylam), showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test (6-MWT), compared with placebo, in the treatment of transthyretin-mediated amyloidosis with cardiomyopathy, in the APOLLO-B trial.

The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.

These positive results, their first formal presentation, were announced Sept. 8 at the 18th International Symposium on Amyloidosis. However, the company announced positive top-line results from the trial in early August.

Transthyretin-mediated (ATTR) amyloidosis is a rare, rapidly progressive, debilitating disease caused by misfolded transthyretin (TTR) proteins which accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal tract.

There are two different types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis, caused by a TTR gene variant, and wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant. hATTR amyloidosis affects approximately 50,000 people worldwide, whereas wtATTR amyloidosis is estimated to affect 200,000-300,000 people worldwide.

Patisiran is an intravenously administered RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. It is also approved in the European Union, Switzerland, Brazil, and Japan for a similar indication. It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues.

“The results of the APOLLO-B phase 3 study are impressive, as I believe they underscore the potential for patisiran to provide a benefit on functional capacity and quality of life in patients living with ATTR amyloidosis with cardiomyopathy. Furthermore, these results were seen after only 12 months of treatment,” Mathew Maurer, MD, Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical Center, New York, said in an Alnylam press release.

“The cardiac manifestations associated with ATTR amyloidosis can have a devastating impact on patients’ lives and current treatment options are limited. With the rapidly progressive nature of the disease, there is a significant need for treatments like patisiran, which has the potential to be a new option for patients and physicians to treat the cardiomyopathy of ATTR amyloidosis,” Dr. Maurer added.

APOLLO-B is a phase 3, randomized, double-blind study evaluating the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The study enrolled 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy who were randomly assigned 1:1 to receive 0.3 mg/kg of patisiran or placebo intravenously administered every 3 weeks over a 12-month treatment period. After 12 months, all patients will receive patisiran in an open-label extension.

Results at 12 months, reported by Alnylam, found that the primary endpoint, the 6-MWT, showed a median change from baseline of –8.15 m for the patisiran group and –21.34 m for the placebo group, a significant difference favoring patisiran.

The first secondary endpoint was health status and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary score. This showed a mean change from baseline of +0.300 for the patisiran group and –3.408 for the placebo group, a significant difference favoring patisiran.

Secondary composite outcome endpoints did not achieve statistical significance.

A nonsignificant result (win ratio, 1.27; P = .0574) was found on the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months, compared with placebo.

The final two composite endpoints were not powered for statistical significance, given the sample size and short duration of the study – all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in patients not on tafamidis at baseline (hazard ratio, 0.997) and in the overall study population (HR, 0.883).

Patisiran achieved a rapid and sustained reduction in serum TTR levels, with a mean percent reduction from baseline in serum TTR reduction of 87% at month 12.

A beneficial effect on the exploratory endpoint, N-terminal of the prohormone brain natriuretic peptide, a measure of cardiac stress, was observed in the patisiran arm, with a 20% reduction in the adjusted geometric mean fold change from baseline, compared with placebo.

Patisiran also demonstrated an encouraging safety and tolerability profile, including no cardiac safety concerns relative to placebo, during the 12-month treatment period, Alnylam reported.

The majority of adverse events were mild or moderate in severity. Treatment emergent adverse events in the patisiran group included infusion-related reactions, arthralgia, and muscle spasms.

In the safety analysis, there were five deaths (2.8%) observed in patisiran-treated patients and eight deaths (4.5%) observed in the placebo group.

Pushkal Garg, MD, chief medical officer at Alnylam, said: “We believe these data validate the therapeutic hypothesis that TTR silencing by an RNAi therapeutic may be an effective approach to treating cardiomyopathy of both wild-type and hereditary ATTR amyloidosis.”

Alnylam plans to file a supplemental new drug application for patisiran as a potential treatment for ATTR amyloidosis with cardiomyopathy in the United States in late 2022.

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

The RNA interference (RNAi) therapeutic, patisiran (Onpattro, Alnylam), showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test (6-MWT), compared with placebo, in the treatment of transthyretin-mediated amyloidosis with cardiomyopathy, in the APOLLO-B trial.

The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.

These positive results, their first formal presentation, were announced Sept. 8 at the 18th International Symposium on Amyloidosis. However, the company announced positive top-line results from the trial in early August.

Transthyretin-mediated (ATTR) amyloidosis is a rare, rapidly progressive, debilitating disease caused by misfolded transthyretin (TTR) proteins which accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal tract.

There are two different types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis, caused by a TTR gene variant, and wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant. hATTR amyloidosis affects approximately 50,000 people worldwide, whereas wtATTR amyloidosis is estimated to affect 200,000-300,000 people worldwide.

Patisiran is an intravenously administered RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. It is also approved in the European Union, Switzerland, Brazil, and Japan for a similar indication. It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues.

“The results of the APOLLO-B phase 3 study are impressive, as I believe they underscore the potential for patisiran to provide a benefit on functional capacity and quality of life in patients living with ATTR amyloidosis with cardiomyopathy. Furthermore, these results were seen after only 12 months of treatment,” Mathew Maurer, MD, Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical Center, New York, said in an Alnylam press release.

“The cardiac manifestations associated with ATTR amyloidosis can have a devastating impact on patients’ lives and current treatment options are limited. With the rapidly progressive nature of the disease, there is a significant need for treatments like patisiran, which has the potential to be a new option for patients and physicians to treat the cardiomyopathy of ATTR amyloidosis,” Dr. Maurer added.

APOLLO-B is a phase 3, randomized, double-blind study evaluating the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The study enrolled 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy who were randomly assigned 1:1 to receive 0.3 mg/kg of patisiran or placebo intravenously administered every 3 weeks over a 12-month treatment period. After 12 months, all patients will receive patisiran in an open-label extension.

Results at 12 months, reported by Alnylam, found that the primary endpoint, the 6-MWT, showed a median change from baseline of –8.15 m for the patisiran group and –21.34 m for the placebo group, a significant difference favoring patisiran.

The first secondary endpoint was health status and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary score. This showed a mean change from baseline of +0.300 for the patisiran group and –3.408 for the placebo group, a significant difference favoring patisiran.

Secondary composite outcome endpoints did not achieve statistical significance.

A nonsignificant result (win ratio, 1.27; P = .0574) was found on the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months, compared with placebo.

The final two composite endpoints were not powered for statistical significance, given the sample size and short duration of the study – all-cause mortality and frequency of all-cause hospitalizations and urgent heart failure visits in patients not on tafamidis at baseline (hazard ratio, 0.997) and in the overall study population (HR, 0.883).

Patisiran achieved a rapid and sustained reduction in serum TTR levels, with a mean percent reduction from baseline in serum TTR reduction of 87% at month 12.

A beneficial effect on the exploratory endpoint, N-terminal of the prohormone brain natriuretic peptide, a measure of cardiac stress, was observed in the patisiran arm, with a 20% reduction in the adjusted geometric mean fold change from baseline, compared with placebo.

Patisiran also demonstrated an encouraging safety and tolerability profile, including no cardiac safety concerns relative to placebo, during the 12-month treatment period, Alnylam reported.

The majority of adverse events were mild or moderate in severity. Treatment emergent adverse events in the patisiran group included infusion-related reactions, arthralgia, and muscle spasms.

In the safety analysis, there were five deaths (2.8%) observed in patisiran-treated patients and eight deaths (4.5%) observed in the placebo group.

Pushkal Garg, MD, chief medical officer at Alnylam, said: “We believe these data validate the therapeutic hypothesis that TTR silencing by an RNAi therapeutic may be an effective approach to treating cardiomyopathy of both wild-type and hereditary ATTR amyloidosis.”

Alnylam plans to file a supplemental new drug application for patisiran as a potential treatment for ATTR amyloidosis with cardiomyopathy in the United States in late 2022.

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

The Food and Drug Administration is alerting health care providers about the potential for clip lock malfunctions with Abbott’s MitraClip’s delivery system.

“These events appear to occur in approximately 1.3% of MitraClip procedures and have been observed with all device models,” the FDA says in a letter posted on its website.

The MitraClip device was approved in 2013 for patients with symptomatic, degenerative mitral regurgitation (MR) deemed high risk for mitral-valve surgery.

In its own “urgent medical device correction letter” to providers, Abbott reports a recent increase in reports of the clips failing to “establish final arm angle (EFAA)” and of “clip opening while locked (COWL)” events.

During device preparation and prior to clip deployment, the operator intentionally attempts to open a locked clip to verify that the locking mechanism is engaged.

COWL describes when the clip arm angle increases postdeployment. “In these cases, users observe a slippage in the lock, resulting in an arm angle greater than 10 degrees from the angle observed at deployment,” which can be identified through fluoroscopy, Abbott says.

From February 2021 to January 2022, the EFAA failure rate was 0.51% and COWL rate 0.28%, increasing to 0.80% and 0.50%, respectively, from February 2022 to July 2022, according to the company.

Despite the increase in reports, the acute procedural success rate remains consistent with historical data, according to Abbott. “Further, EFAA failure or COWL most often results in no adverse patient outcomes. COWL may lead to less MR reduction, which is often treated with the use of one or more additional clips.”

Abbott says there is also a “low incidence” of required additional interventions. No immediate open surgical conversions have occurred as a result of EFAA/COWL events, whereas 0.53% of such events have resulted in nonurgent surgical conversions.

“In any case where significant residual MR is observed after clip deployment, a second clip should be considered and implanted in accordance with the IFU [instructions for use],” it advises.

Abbott says that a “change in the material properties of one of the clip locking components” has been identified as a contributing cause of EFAA/COWL events. It is working on producing new lots with updated manufacturing processing and raw material to mitigate the risk.

Certain use conditions can also contribute to EFAA/COWL events, and are referenced in the IFU, Appendix A, it notes.

The FDA is working with Abbott and recommends that health care providers do the following:

• Review the recall notice from Abbott for all MitraClip Clip Delivery Systems.
• Be aware of the potential for clip lock malfunctions before or after deployment with this device.
• Read and carefully follow the instructions for use and the recommendations provided in the recall notice to help minimize the chance of the clip failing to lock. These include recommendations about procedural steps for implant positioning, locking sequences, establishing clip arm angle, preparation for clip release, and avoiding excessive force and manipulation when unlocking the clip during device preparation and during the procedure.

Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

The Food and Drug Administration is alerting health care providers about the potential for clip lock malfunctions with Abbott’s MitraClip’s delivery system.

“These events appear to occur in approximately 1.3% of MitraClip procedures and have been observed with all device models,” the FDA says in a letter posted on its website.

The MitraClip device was approved in 2013 for patients with symptomatic, degenerative mitral regurgitation (MR) deemed high risk for mitral-valve surgery.

In its own “urgent medical device correction letter” to providers, Abbott reports a recent increase in reports of the clips failing to “establish final arm angle (EFAA)” and of “clip opening while locked (COWL)” events.

During device preparation and prior to clip deployment, the operator intentionally attempts to open a locked clip to verify that the locking mechanism is engaged.

COWL describes when the clip arm angle increases postdeployment. “In these cases, users observe a slippage in the lock, resulting in an arm angle greater than 10 degrees from the angle observed at deployment,” which can be identified through fluoroscopy, Abbott says.

From February 2021 to January 2022, the EFAA failure rate was 0.51% and COWL rate 0.28%, increasing to 0.80% and 0.50%, respectively, from February 2022 to July 2022, according to the company.

Despite the increase in reports, the acute procedural success rate remains consistent with historical data, according to Abbott. “Further, EFAA failure or COWL most often results in no adverse patient outcomes. COWL may lead to less MR reduction, which is often treated with the use of one or more additional clips.”

Abbott says there is also a “low incidence” of required additional interventions. No immediate open surgical conversions have occurred as a result of EFAA/COWL events, whereas 0.53% of such events have resulted in nonurgent surgical conversions.

“In any case where significant residual MR is observed after clip deployment, a second clip should be considered and implanted in accordance with the IFU [instructions for use],” it advises.

Abbott says that a “change in the material properties of one of the clip locking components” has been identified as a contributing cause of EFAA/COWL events. It is working on producing new lots with updated manufacturing processing and raw material to mitigate the risk.

Certain use conditions can also contribute to EFAA/COWL events, and are referenced in the IFU, Appendix A, it notes.

The FDA is working with Abbott and recommends that health care providers do the following:

• Review the recall notice from Abbott for all MitraClip Clip Delivery Systems.
• Be aware of the potential for clip lock malfunctions before or after deployment with this device.
• Read and carefully follow the instructions for use and the recommendations provided in the recall notice to help minimize the chance of the clip failing to lock. These include recommendations about procedural steps for implant positioning, locking sequences, establishing clip arm angle, preparation for clip release, and avoiding excessive force and manipulation when unlocking the clip during device preparation and during the procedure.

Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

The Food and Drug Administration is alerting health care providers about the potential for clip lock malfunctions with Abbott’s MitraClip’s delivery system.

“These events appear to occur in approximately 1.3% of MitraClip procedures and have been observed with all device models,” the FDA says in a letter posted on its website.

The MitraClip device was approved in 2013 for patients with symptomatic, degenerative mitral regurgitation (MR) deemed high risk for mitral-valve surgery.

In its own “urgent medical device correction letter” to providers, Abbott reports a recent increase in reports of the clips failing to “establish final arm angle (EFAA)” and of “clip opening while locked (COWL)” events.

During device preparation and prior to clip deployment, the operator intentionally attempts to open a locked clip to verify that the locking mechanism is engaged.

COWL describes when the clip arm angle increases postdeployment. “In these cases, users observe a slippage in the lock, resulting in an arm angle greater than 10 degrees from the angle observed at deployment,” which can be identified through fluoroscopy, Abbott says.

From February 2021 to January 2022, the EFAA failure rate was 0.51% and COWL rate 0.28%, increasing to 0.80% and 0.50%, respectively, from February 2022 to July 2022, according to the company.

Despite the increase in reports, the acute procedural success rate remains consistent with historical data, according to Abbott. “Further, EFAA failure or COWL most often results in no adverse patient outcomes. COWL may lead to less MR reduction, which is often treated with the use of one or more additional clips.”

Abbott says there is also a “low incidence” of required additional interventions. No immediate open surgical conversions have occurred as a result of EFAA/COWL events, whereas 0.53% of such events have resulted in nonurgent surgical conversions.

“In any case where significant residual MR is observed after clip deployment, a second clip should be considered and implanted in accordance with the IFU [instructions for use],” it advises.

Abbott says that a “change in the material properties of one of the clip locking components” has been identified as a contributing cause of EFAA/COWL events. It is working on producing new lots with updated manufacturing processing and raw material to mitigate the risk.

Certain use conditions can also contribute to EFAA/COWL events, and are referenced in the IFU, Appendix A, it notes.

The FDA is working with Abbott and recommends that health care providers do the following:

• Review the recall notice from Abbott for all MitraClip Clip Delivery Systems.
• Be aware of the potential for clip lock malfunctions before or after deployment with this device.
• Read and carefully follow the instructions for use and the recommendations provided in the recall notice to help minimize the chance of the clip failing to lock. These include recommendations about procedural steps for implant positioning, locking sequences, establishing clip arm angle, preparation for clip release, and avoiding excessive force and manipulation when unlocking the clip during device preparation and during the procedure.

Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

Health concerns about the consumption of artificial sweeteners could be strengthened with the publication of a new study linking their intake to increased risk of heart disease and stroke events.

In this latest large-scale, prospective study of French adults, total artificial sweetener intake from all sources was associated with increased risk overall of cardiovascular and cerebrovascular disease.

The study was published online in the BMJ.

The current study differs from those done previously in that it includes artificial sweetener intake from both food and drinks, whereas previous studies have focused mainly on artificial sweetener content of beverages alone.

“Here we have quantified for the first time the global exposure to artificial sweeteners. This is not just beverages but includes the use of tabletop sweeteners, and other foods that include artificial sweeteners such as yogurts and desserts. This is the first time this information has been correlated to risk of heart disease,” senior author Mathilde Touvier, MD, Sorbonne Paris Nord University, told this news organization.

Just over half of the artificial sweetener intake in the study came from drinks, with the rest coming from tabletop sweeteners and foods.

“We included hard cardio- and cerebrovascular clinical endpoints such as a heart attack or stroke, and our results suggest that the amount of artificial sweetener in less than one can of soda could increase the risk of such events,” Dr. Touvier noted.

“This is an important and statistically significant association which shows robustness in all models after adjusting for many other possible confounding factors,” she said.

“There is now mounting evidence correlating artificial sweeteners to weight gain and heart disease,” she concluded. “My advice would be that we all need to try to limit sugar intake, but we should not consider artificial sweeteners as safe alternatives. Rather, we need to try to reduce our need for a sugary taste in our diet.”

But another leading researcher in the field urges caution in interpreting these results.

John Sievenpiper, MD, departments of nutritional sciences and medicine, University of Toronto, commented: “This paper shows the same relationship seen by many other large prospective cohorts which model the intake of artificial sweeteners as baseline or prevalent exposures.

“These observations are well recognized to be at high risk of residual confounding from behavior clustering and reverse causality in which being at risk for cardiovascular disease causes people to consume artificial sweeteners as a strategy to mitigate this risk as opposed to the other way around.”
 

Risk increased by 9%

The current study included 103,388 French adults from the NutriNet-Sante cohort, of whom 37.1% reported consumption of artificial sweeteners. The sweeteners assessed were mainly aspartame (58% of sweetener intake), acesulfame potassium (29%), and sucralose (10%), with the other 3% made up of various other sweeteners including cyclamates and saccharin.

Results showed that over an average 9 years of follow-up, artificial sweetener intake was associated with a 9% increased risk of cardiovascular or cerebrovascular events, including myocardial infarction, acute coronary syndrome, angioplasty, angina, stroke, or transient ischemic attack, with a hazard ratio of 1.09 (95% confidence interval, 1.01-1.18; P = .03).

The average intake of artificial sweeteners among those who reported consuming them was 42.46 mg/day, which corresponds to approximately one individual packet of tabletop sweetener or 100 mL of diet soda.

“We don’t have enough evidence to work out an amount of artificial sweetener that is harmful, but we did show a dose-effect association, with a higher risk of cardiovascular events with higher consumption,” Dr. Touvier said.

“Higher consumption in this study was a mean of 77 mg/day artificial sweetener, which is about 200 mL of soda – just a bit less than one standard can of soda,” she added.

The absolute incidence rate of cardiovascular or cerebrovascular events in higher consumers was 346 per 100,000 person-years vs. 314 per 100,000 person-years in nonconsumers.

Further analysis suggested that aspartame intake was particularly associated with increased risk of cerebrovascular events, while acesulfame potassium and sucralose were associated with increased coronary heart disease risk.
 

Study strengths

Dr. Touvier acknowledged that dietary studies, which generally rely on individuals self-reporting food and drink intake, are always hard to interpret. But she said this study used a more reliable method of dietary assessment, with repeated 24-hour dietary records, which were validated by interviews with a trained dietitian and against blood and urinary biomarkers.

And whereas residual confounding cannot be totally excluded, she pointed out that models were adjusted for a wide range of potential sociodemographic, anthropometric, dietary, and lifestyle confounders.

Dr. Touvier also noted that cases of cardiovascular disease in the first 2 years of follow-up were excluded to minimize the bias caused by individuals who maybe have switched to artificial sweeteners because of a cardiovascular issue.

“While this study has many strengths, it cannot on its own prove a causal relationship between artificial sweetener and increased cardiovascular risk,” she added. “We need health agencies to examine all the literature in the field. This is however another important piece of evidence.”

Dr. Touvier says that although observational studies have their issues, they will form the basis of the evidence on the effects of artificial sweeteners on health.

“Randomized studies in this area can only really look at short-term outcomes such as weight gain or biomarker changes. So, we will have to use observational studies together with experimental research to build the evidence. This is what happened with cigarette smoking and lung cancer. That link was not established by randomized trials, but by the accumulation of observational and experimental data.”
 

Different artificial sweeteners may be better?

Commenting on the study, Kim Williams Sr., MD, University of Louisville (Ky.), pointed out that this study included artificial sweeteners that increase insulin or decrease insulin sensitivity, and that insulin spikes increase obesity, insulin resistance, hypertension, and atherosclerosis.

“There are some safer artificial sweeteners that do not increase insulin much or at all, such as erythritol, yacon root/yacon syrup, stevia root, but they weren’t included in the analysis,” Dr. Williams added.

Dr. Sievenpiper explained that most studies on artificial sweeteners look at their consumption in isolation without considering how they compare to the intake of the sugars that they are intended to replace.

“The comparator matters as no food is consumed in a vacuum,” he said.

To address this, Dr. Sievenpiper and colleagues have recently published a systematic review and meta-analysis of the prospective cohort study evidence that shows if exposure to artificially sweetened beverages is modeled in substitution for sugar-sweetened beverages, then they are associated with less coronary heart disease, cardiovascular mortality, and all-cause mortality.

On the other hand, if exposure to artificially sweetened beverages is compared with water, then no difference in these outcomes was seen.

“These observations are more biologically plausible, robust, and reproducible and agree with the evidence for the effect of artificial sweeteners on intermediate risk factors in randomized trials,” Dr. Sievenpiper notes.

His group has also recently published a review of randomized studies showing that when compared with sugar-sweetened beverages, intake of artificially sweetened beverages was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm.

“I think the context provided by these studies is important, and taken together, the totality of the evidence suggests that artificial sweeteners are likely to be a useful tool in sugar reduction strategies,” Dr. Sievenpiper concludes.

The current study was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program, French National Cancer Institute, French Ministry of Health, IdEx Université de Paris Cité, Bettencourt-Schueller Foundation Research Prize 2021. The authors have disclosed no relevant financial relationships.

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

Health concerns about the consumption of artificial sweeteners could be strengthened with the publication of a new study linking their intake to increased risk of heart disease and stroke events.

In this latest large-scale, prospective study of French adults, total artificial sweetener intake from all sources was associated with increased risk overall of cardiovascular and cerebrovascular disease.

The study was published online in the BMJ.

The current study differs from those done previously in that it includes artificial sweetener intake from both food and drinks, whereas previous studies have focused mainly on artificial sweetener content of beverages alone.

“Here we have quantified for the first time the global exposure to artificial sweeteners. This is not just beverages but includes the use of tabletop sweeteners, and other foods that include artificial sweeteners such as yogurts and desserts. This is the first time this information has been correlated to risk of heart disease,” senior author Mathilde Touvier, MD, Sorbonne Paris Nord University, told this news organization.

Just over half of the artificial sweetener intake in the study came from drinks, with the rest coming from tabletop sweeteners and foods.

“We included hard cardio- and cerebrovascular clinical endpoints such as a heart attack or stroke, and our results suggest that the amount of artificial sweetener in less than one can of soda could increase the risk of such events,” Dr. Touvier noted.

“This is an important and statistically significant association which shows robustness in all models after adjusting for many other possible confounding factors,” she said.

“There is now mounting evidence correlating artificial sweeteners to weight gain and heart disease,” she concluded. “My advice would be that we all need to try to limit sugar intake, but we should not consider artificial sweeteners as safe alternatives. Rather, we need to try to reduce our need for a sugary taste in our diet.”

But another leading researcher in the field urges caution in interpreting these results.

John Sievenpiper, MD, departments of nutritional sciences and medicine, University of Toronto, commented: “This paper shows the same relationship seen by many other large prospective cohorts which model the intake of artificial sweeteners as baseline or prevalent exposures.

“These observations are well recognized to be at high risk of residual confounding from behavior clustering and reverse causality in which being at risk for cardiovascular disease causes people to consume artificial sweeteners as a strategy to mitigate this risk as opposed to the other way around.”
 

Risk increased by 9%

The current study included 103,388 French adults from the NutriNet-Sante cohort, of whom 37.1% reported consumption of artificial sweeteners. The sweeteners assessed were mainly aspartame (58% of sweetener intake), acesulfame potassium (29%), and sucralose (10%), with the other 3% made up of various other sweeteners including cyclamates and saccharin.

Results showed that over an average 9 years of follow-up, artificial sweetener intake was associated with a 9% increased risk of cardiovascular or cerebrovascular events, including myocardial infarction, acute coronary syndrome, angioplasty, angina, stroke, or transient ischemic attack, with a hazard ratio of 1.09 (95% confidence interval, 1.01-1.18; P = .03).

The average intake of artificial sweeteners among those who reported consuming them was 42.46 mg/day, which corresponds to approximately one individual packet of tabletop sweetener or 100 mL of diet soda.

“We don’t have enough evidence to work out an amount of artificial sweetener that is harmful, but we did show a dose-effect association, with a higher risk of cardiovascular events with higher consumption,” Dr. Touvier said.

“Higher consumption in this study was a mean of 77 mg/day artificial sweetener, which is about 200 mL of soda – just a bit less than one standard can of soda,” she added.

The absolute incidence rate of cardiovascular or cerebrovascular events in higher consumers was 346 per 100,000 person-years vs. 314 per 100,000 person-years in nonconsumers.

Further analysis suggested that aspartame intake was particularly associated with increased risk of cerebrovascular events, while acesulfame potassium and sucralose were associated with increased coronary heart disease risk.
 

Study strengths

Dr. Touvier acknowledged that dietary studies, which generally rely on individuals self-reporting food and drink intake, are always hard to interpret. But she said this study used a more reliable method of dietary assessment, with repeated 24-hour dietary records, which were validated by interviews with a trained dietitian and against blood and urinary biomarkers.

And whereas residual confounding cannot be totally excluded, she pointed out that models were adjusted for a wide range of potential sociodemographic, anthropometric, dietary, and lifestyle confounders.

Dr. Touvier also noted that cases of cardiovascular disease in the first 2 years of follow-up were excluded to minimize the bias caused by individuals who maybe have switched to artificial sweeteners because of a cardiovascular issue.

“While this study has many strengths, it cannot on its own prove a causal relationship between artificial sweetener and increased cardiovascular risk,” she added. “We need health agencies to examine all the literature in the field. This is however another important piece of evidence.”

Dr. Touvier says that although observational studies have their issues, they will form the basis of the evidence on the effects of artificial sweeteners on health.

“Randomized studies in this area can only really look at short-term outcomes such as weight gain or biomarker changes. So, we will have to use observational studies together with experimental research to build the evidence. This is what happened with cigarette smoking and lung cancer. That link was not established by randomized trials, but by the accumulation of observational and experimental data.”
 

Different artificial sweeteners may be better?

Commenting on the study, Kim Williams Sr., MD, University of Louisville (Ky.), pointed out that this study included artificial sweeteners that increase insulin or decrease insulin sensitivity, and that insulin spikes increase obesity, insulin resistance, hypertension, and atherosclerosis.

“There are some safer artificial sweeteners that do not increase insulin much or at all, such as erythritol, yacon root/yacon syrup, stevia root, but they weren’t included in the analysis,” Dr. Williams added.

Dr. Sievenpiper explained that most studies on artificial sweeteners look at their consumption in isolation without considering how they compare to the intake of the sugars that they are intended to replace.

“The comparator matters as no food is consumed in a vacuum,” he said.

To address this, Dr. Sievenpiper and colleagues have recently published a systematic review and meta-analysis of the prospective cohort study evidence that shows if exposure to artificially sweetened beverages is modeled in substitution for sugar-sweetened beverages, then they are associated with less coronary heart disease, cardiovascular mortality, and all-cause mortality.

On the other hand, if exposure to artificially sweetened beverages is compared with water, then no difference in these outcomes was seen.

“These observations are more biologically plausible, robust, and reproducible and agree with the evidence for the effect of artificial sweeteners on intermediate risk factors in randomized trials,” Dr. Sievenpiper notes.

His group has also recently published a review of randomized studies showing that when compared with sugar-sweetened beverages, intake of artificially sweetened beverages was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm.

“I think the context provided by these studies is important, and taken together, the totality of the evidence suggests that artificial sweeteners are likely to be a useful tool in sugar reduction strategies,” Dr. Sievenpiper concludes.

The current study was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program, French National Cancer Institute, French Ministry of Health, IdEx Université de Paris Cité, Bettencourt-Schueller Foundation Research Prize 2021. The authors have disclosed no relevant financial relationships.

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

Health concerns about the consumption of artificial sweeteners could be strengthened with the publication of a new study linking their intake to increased risk of heart disease and stroke events.

In this latest large-scale, prospective study of French adults, total artificial sweetener intake from all sources was associated with increased risk overall of cardiovascular and cerebrovascular disease.

The study was published online in the BMJ.

The current study differs from those done previously in that it includes artificial sweetener intake from both food and drinks, whereas previous studies have focused mainly on artificial sweetener content of beverages alone.

“Here we have quantified for the first time the global exposure to artificial sweeteners. This is not just beverages but includes the use of tabletop sweeteners, and other foods that include artificial sweeteners such as yogurts and desserts. This is the first time this information has been correlated to risk of heart disease,” senior author Mathilde Touvier, MD, Sorbonne Paris Nord University, told this news organization.

Just over half of the artificial sweetener intake in the study came from drinks, with the rest coming from tabletop sweeteners and foods.

“We included hard cardio- and cerebrovascular clinical endpoints such as a heart attack or stroke, and our results suggest that the amount of artificial sweetener in less than one can of soda could increase the risk of such events,” Dr. Touvier noted.

“This is an important and statistically significant association which shows robustness in all models after adjusting for many other possible confounding factors,” she said.

“There is now mounting evidence correlating artificial sweeteners to weight gain and heart disease,” she concluded. “My advice would be that we all need to try to limit sugar intake, but we should not consider artificial sweeteners as safe alternatives. Rather, we need to try to reduce our need for a sugary taste in our diet.”

But another leading researcher in the field urges caution in interpreting these results.

John Sievenpiper, MD, departments of nutritional sciences and medicine, University of Toronto, commented: “This paper shows the same relationship seen by many other large prospective cohorts which model the intake of artificial sweeteners as baseline or prevalent exposures.

“These observations are well recognized to be at high risk of residual confounding from behavior clustering and reverse causality in which being at risk for cardiovascular disease causes people to consume artificial sweeteners as a strategy to mitigate this risk as opposed to the other way around.”
 

Risk increased by 9%

The current study included 103,388 French adults from the NutriNet-Sante cohort, of whom 37.1% reported consumption of artificial sweeteners. The sweeteners assessed were mainly aspartame (58% of sweetener intake), acesulfame potassium (29%), and sucralose (10%), with the other 3% made up of various other sweeteners including cyclamates and saccharin.

Results showed that over an average 9 years of follow-up, artificial sweetener intake was associated with a 9% increased risk of cardiovascular or cerebrovascular events, including myocardial infarction, acute coronary syndrome, angioplasty, angina, stroke, or transient ischemic attack, with a hazard ratio of 1.09 (95% confidence interval, 1.01-1.18; P = .03).

The average intake of artificial sweeteners among those who reported consuming them was 42.46 mg/day, which corresponds to approximately one individual packet of tabletop sweetener or 100 mL of diet soda.

“We don’t have enough evidence to work out an amount of artificial sweetener that is harmful, but we did show a dose-effect association, with a higher risk of cardiovascular events with higher consumption,” Dr. Touvier said.

“Higher consumption in this study was a mean of 77 mg/day artificial sweetener, which is about 200 mL of soda – just a bit less than one standard can of soda,” she added.

The absolute incidence rate of cardiovascular or cerebrovascular events in higher consumers was 346 per 100,000 person-years vs. 314 per 100,000 person-years in nonconsumers.

Further analysis suggested that aspartame intake was particularly associated with increased risk of cerebrovascular events, while acesulfame potassium and sucralose were associated with increased coronary heart disease risk.
 

Study strengths

Dr. Touvier acknowledged that dietary studies, which generally rely on individuals self-reporting food and drink intake, are always hard to interpret. But she said this study used a more reliable method of dietary assessment, with repeated 24-hour dietary records, which were validated by interviews with a trained dietitian and against blood and urinary biomarkers.

And whereas residual confounding cannot be totally excluded, she pointed out that models were adjusted for a wide range of potential sociodemographic, anthropometric, dietary, and lifestyle confounders.

Dr. Touvier also noted that cases of cardiovascular disease in the first 2 years of follow-up were excluded to minimize the bias caused by individuals who maybe have switched to artificial sweeteners because of a cardiovascular issue.

“While this study has many strengths, it cannot on its own prove a causal relationship between artificial sweetener and increased cardiovascular risk,” she added. “We need health agencies to examine all the literature in the field. This is however another important piece of evidence.”

Dr. Touvier says that although observational studies have their issues, they will form the basis of the evidence on the effects of artificial sweeteners on health.

“Randomized studies in this area can only really look at short-term outcomes such as weight gain or biomarker changes. So, we will have to use observational studies together with experimental research to build the evidence. This is what happened with cigarette smoking and lung cancer. That link was not established by randomized trials, but by the accumulation of observational and experimental data.”
 

Different artificial sweeteners may be better?

Commenting on the study, Kim Williams Sr., MD, University of Louisville (Ky.), pointed out that this study included artificial sweeteners that increase insulin or decrease insulin sensitivity, and that insulin spikes increase obesity, insulin resistance, hypertension, and atherosclerosis.

“There are some safer artificial sweeteners that do not increase insulin much or at all, such as erythritol, yacon root/yacon syrup, stevia root, but they weren’t included in the analysis,” Dr. Williams added.

Dr. Sievenpiper explained that most studies on artificial sweeteners look at their consumption in isolation without considering how they compare to the intake of the sugars that they are intended to replace.

“The comparator matters as no food is consumed in a vacuum,” he said.

To address this, Dr. Sievenpiper and colleagues have recently published a systematic review and meta-analysis of the prospective cohort study evidence that shows if exposure to artificially sweetened beverages is modeled in substitution for sugar-sweetened beverages, then they are associated with less coronary heart disease, cardiovascular mortality, and all-cause mortality.

On the other hand, if exposure to artificially sweetened beverages is compared with water, then no difference in these outcomes was seen.

“These observations are more biologically plausible, robust, and reproducible and agree with the evidence for the effect of artificial sweeteners on intermediate risk factors in randomized trials,” Dr. Sievenpiper notes.

His group has also recently published a review of randomized studies showing that when compared with sugar-sweetened beverages, intake of artificially sweetened beverages was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm.

“I think the context provided by these studies is important, and taken together, the totality of the evidence suggests that artificial sweeteners are likely to be a useful tool in sugar reduction strategies,” Dr. Sievenpiper concludes.

The current study was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program, French National Cancer Institute, French Ministry of Health, IdEx Université de Paris Cité, Bettencourt-Schueller Foundation Research Prize 2021. The authors have disclosed no relevant financial relationships.

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

Imagine that instead of a patient visiting their doctor for blood tests, they could rely on a noninvasive at-home test to predict their risk of diabetes, a disease that affects nearly 15% of U.S. adults (23% of whom are undiagnosed), according to the U.S. Centers for Disease Control and Prevention.

This technology could become a reality thanks to a research team that developed a machine learning algorithm to predict whether people had type 2 diabetes, prediabetes, or no diabetes. In an article published in BMJ Innovations, the researchers describe how their algorithm sorted people into these three categories with 97% accuracy on the basis of measurements of the heart’s electrical activity, determined from an electrocardiogram.

To develop and train their machine learning model – a type of artificial intelligence (AI) that keeps getting smarter over time – researchers used ECG measurements from 1,262 people in Central India. The study participants were part of the Sindhi population, an ethnic group that has been shown in past studies to be at elevated risk for type 2 diabetes.

Why ECG data? Because “cardiovascular abnormalities and diabetes, they go hand in hand,” says study author Manju Mamtani, MD, general manager of M&H Research, San Antonio, and treasurer of the Lata Medical Research Foundation. Subtle cardiovascular changes can occur even early in the development of diabetes.

“ECG has the power to detect these fluctuations, at least in theory, but those fluctuations are so tiny that many times we as humans looking at that might miss it,” says study author Hemant Kulkarni, MD, chief executive officer of M&H Research and president of the Lata Medical Research Foundation. “But the AI, which is powered to detect such specific fluctuations or subtle features, we hypothesized for the study that the AI algorithm might be able to pick those things up. And it did.”

Although this isn’t the first AI algorithm developed to predict diabetes risk, it outperforms previous models, the researchers say.

The team hopes to test and validate the algorithm in a variety of populations so that it can eventually be developed into an accessible, user-friendly technology. They envision that someday their algorithm could be used in smartwatches or other smart devices and could be integrated into telehealth so that people could be screened for diabetes even if they weren’t able to travel to a health care facility for blood testing.

The team is also studying other noninvasive methods of early disease detection and predictive models for adverse outcomes using AI.

“The fact that these algorithms are able to pick up the things of interest and learn on their own and keep learning in the future also adds excitement to their use in these settings,” says Dr. Kulkarni.

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

Imagine that instead of a patient visiting their doctor for blood tests, they could rely on a noninvasive at-home test to predict their risk of diabetes, a disease that affects nearly 15% of U.S. adults (23% of whom are undiagnosed), according to the U.S. Centers for Disease Control and Prevention.

This technology could become a reality thanks to a research team that developed a machine learning algorithm to predict whether people had type 2 diabetes, prediabetes, or no diabetes. In an article published in BMJ Innovations, the researchers describe how their algorithm sorted people into these three categories with 97% accuracy on the basis of measurements of the heart’s electrical activity, determined from an electrocardiogram.

To develop and train their machine learning model – a type of artificial intelligence (AI) that keeps getting smarter over time – researchers used ECG measurements from 1,262 people in Central India. The study participants were part of the Sindhi population, an ethnic group that has been shown in past studies to be at elevated risk for type 2 diabetes.

Why ECG data? Because “cardiovascular abnormalities and diabetes, they go hand in hand,” says study author Manju Mamtani, MD, general manager of M&H Research, San Antonio, and treasurer of the Lata Medical Research Foundation. Subtle cardiovascular changes can occur even early in the development of diabetes.

“ECG has the power to detect these fluctuations, at least in theory, but those fluctuations are so tiny that many times we as humans looking at that might miss it,” says study author Hemant Kulkarni, MD, chief executive officer of M&H Research and president of the Lata Medical Research Foundation. “But the AI, which is powered to detect such specific fluctuations or subtle features, we hypothesized for the study that the AI algorithm might be able to pick those things up. And it did.”

Although this isn’t the first AI algorithm developed to predict diabetes risk, it outperforms previous models, the researchers say.

The team hopes to test and validate the algorithm in a variety of populations so that it can eventually be developed into an accessible, user-friendly technology. They envision that someday their algorithm could be used in smartwatches or other smart devices and could be integrated into telehealth so that people could be screened for diabetes even if they weren’t able to travel to a health care facility for blood testing.

The team is also studying other noninvasive methods of early disease detection and predictive models for adverse outcomes using AI.

“The fact that these algorithms are able to pick up the things of interest and learn on their own and keep learning in the future also adds excitement to their use in these settings,” says Dr. Kulkarni.

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

Imagine that instead of a patient visiting their doctor for blood tests, they could rely on a noninvasive at-home test to predict their risk of diabetes, a disease that affects nearly 15% of U.S. adults (23% of whom are undiagnosed), according to the U.S. Centers for Disease Control and Prevention.

This technology could become a reality thanks to a research team that developed a machine learning algorithm to predict whether people had type 2 diabetes, prediabetes, or no diabetes. In an article published in BMJ Innovations, the researchers describe how their algorithm sorted people into these three categories with 97% accuracy on the basis of measurements of the heart’s electrical activity, determined from an electrocardiogram.

To develop and train their machine learning model – a type of artificial intelligence (AI) that keeps getting smarter over time – researchers used ECG measurements from 1,262 people in Central India. The study participants were part of the Sindhi population, an ethnic group that has been shown in past studies to be at elevated risk for type 2 diabetes.

Why ECG data? Because “cardiovascular abnormalities and diabetes, they go hand in hand,” says study author Manju Mamtani, MD, general manager of M&H Research, San Antonio, and treasurer of the Lata Medical Research Foundation. Subtle cardiovascular changes can occur even early in the development of diabetes.

“ECG has the power to detect these fluctuations, at least in theory, but those fluctuations are so tiny that many times we as humans looking at that might miss it,” says study author Hemant Kulkarni, MD, chief executive officer of M&H Research and president of the Lata Medical Research Foundation. “But the AI, which is powered to detect such specific fluctuations or subtle features, we hypothesized for the study that the AI algorithm might be able to pick those things up. And it did.”

Although this isn’t the first AI algorithm developed to predict diabetes risk, it outperforms previous models, the researchers say.

The team hopes to test and validate the algorithm in a variety of populations so that it can eventually be developed into an accessible, user-friendly technology. They envision that someday their algorithm could be used in smartwatches or other smart devices and could be integrated into telehealth so that people could be screened for diabetes even if they weren’t able to travel to a health care facility for blood testing.

The team is also studying other noninvasive methods of early disease detection and predictive models for adverse outcomes using AI.

“The fact that these algorithms are able to pick up the things of interest and learn on their own and keep learning in the future also adds excitement to their use in these settings,” says Dr. Kulkarni.

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

Certain ultraprocessed foods – especially candy, prepackaged pastries, and frozen desserts – could be “gateway foods” for adolescents, leading them to increase their intake of other unhealthy foods, a new study suggests.

“For teens, gateway ultraprocessed foods (candy, store pastries, frozen desserts) should be prioritized for preventive dietary interventions as they increase intake across all other UPFs,” lead researcher Maria Balhara said in an interview.

“The good news,” said Ms. Balhara, is that even small changes, such as reducing how often gateway foods are consumed, may reduce overall intake of unhealthy foods and have a “big impact” on overall health.

Ms. Balhara has a unique perspective on adolescent eating habits: She’s 16 years old, from Florida, and conducted the study while dual-enrolled at Broward College and Cooper City High School.

Her study was released Sept. 7 ahead of presentation at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
 

Blame the pandemic?

Over the past 30 years, there’s been a steady increase in consumption of UPFs worldwide, coupled with mounting evidence that diets rich in UPFs raise the risk for several chronic diseases, including weight gain, hypertension, and increased risk for heart disease and premature death.

For her research, Ms. Balhara asked 315 teenagers (42% male) from 12 high schools in South Florida how often they consumed UPFs over two time periods – before COVID in 2019 and after COVID restrictions were eased in 2022 – using a survey that she developed called the Processed Intake Evaluation (PIE).

More than 2 in 5 teens (43%) increased their consumption of UPFs between 2019 and 2022.

During this time, increased consumption of frozen desserts was associated with an 11% increase in consumption of all other UPFs, whereas increased consumption of prepackaged pastries and candy was associated with a 12% and 31%, respectively, increase in consumption of all other UPFs, Ms. Balhara found.

Encouragingly, 57% of teens decreased their consumption of UPFs between 2019 and 2022.

During this time, decreased consumption of processed meats was associated with an 8% decrease in consumption of all other UPFs, whereas decreased consumption of white bread and biscuits was associated with a 9% and 10%, respectively, decrease in consumption of all other UPFs.

The results provide initial evidence for a new “gateway food model,” Ms. Balhara told this news organization, in which certain UPFs, when increased, drive overall consumption of all UPFs among teens.

Limitations of the study include the self-reported dietary data and the fact that the PIE survey has not been validated.
 

Not all UPFs are bad

“I commend Ms. Balhara for her project, which highlights the importance of establishing good dietary patterns early in life,” Donna K. Arnett, PhD, past president of the AHA, said in a news release.

“The relationship between poor dietary quality and cardiovascular risk factors is well-established. While this is a small, preliminary study, it’s an important topic to continue to investigate and help us understand ways we can influence dietary behaviors to promote optimal cardiovascular health for all ages,” said Dr. Arnett, executive vice president for academic affairs and provost at the University of South Carolina, Columbia.

Offering perspective on the study, Taylor C. Wallace, PhD, with the department of nutrition and food studies, George Mason University, Fairfax, Va., made the point that “food processing and ultraprocessed foods aren’t the problem. The problem is the types of ultraprocessed foods on the market that people consume.”

“Remember, non-fat, vitamin D fortified yogurt is also ‘ultra-processed,’ and it’s very healthy,” he told this news organization.

Dr. Wallace said that it’s no surprise that teens increased their intake of UPFs during the pandemic.

“Of course, people increased processed food intake during the pandemic. Processed foods are shelf stable at a time when grocery stores were running out of things and supply chains weren’t able to keep up. Also, many were depressed and use food to indulge,” he noted.

The study had no funding. Ms. Balhara has no relevant disclosures. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and an advisory board member with Forbes Health.

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

Certain ultraprocessed foods – especially candy, prepackaged pastries, and frozen desserts – could be “gateway foods” for adolescents, leading them to increase their intake of other unhealthy foods, a new study suggests.

“For teens, gateway ultraprocessed foods (candy, store pastries, frozen desserts) should be prioritized for preventive dietary interventions as they increase intake across all other UPFs,” lead researcher Maria Balhara said in an interview.

“The good news,” said Ms. Balhara, is that even small changes, such as reducing how often gateway foods are consumed, may reduce overall intake of unhealthy foods and have a “big impact” on overall health.

Ms. Balhara has a unique perspective on adolescent eating habits: She’s 16 years old, from Florida, and conducted the study while dual-enrolled at Broward College and Cooper City High School.

Her study was released Sept. 7 ahead of presentation at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
 

Blame the pandemic?

Over the past 30 years, there’s been a steady increase in consumption of UPFs worldwide, coupled with mounting evidence that diets rich in UPFs raise the risk for several chronic diseases, including weight gain, hypertension, and increased risk for heart disease and premature death.

For her research, Ms. Balhara asked 315 teenagers (42% male) from 12 high schools in South Florida how often they consumed UPFs over two time periods – before COVID in 2019 and after COVID restrictions were eased in 2022 – using a survey that she developed called the Processed Intake Evaluation (PIE).

More than 2 in 5 teens (43%) increased their consumption of UPFs between 2019 and 2022.

During this time, increased consumption of frozen desserts was associated with an 11% increase in consumption of all other UPFs, whereas increased consumption of prepackaged pastries and candy was associated with a 12% and 31%, respectively, increase in consumption of all other UPFs, Ms. Balhara found.

Encouragingly, 57% of teens decreased their consumption of UPFs between 2019 and 2022.

During this time, decreased consumption of processed meats was associated with an 8% decrease in consumption of all other UPFs, whereas decreased consumption of white bread and biscuits was associated with a 9% and 10%, respectively, decrease in consumption of all other UPFs.

The results provide initial evidence for a new “gateway food model,” Ms. Balhara told this news organization, in which certain UPFs, when increased, drive overall consumption of all UPFs among teens.

Limitations of the study include the self-reported dietary data and the fact that the PIE survey has not been validated.
 

Not all UPFs are bad

“I commend Ms. Balhara for her project, which highlights the importance of establishing good dietary patterns early in life,” Donna K. Arnett, PhD, past president of the AHA, said in a news release.

“The relationship between poor dietary quality and cardiovascular risk factors is well-established. While this is a small, preliminary study, it’s an important topic to continue to investigate and help us understand ways we can influence dietary behaviors to promote optimal cardiovascular health for all ages,” said Dr. Arnett, executive vice president for academic affairs and provost at the University of South Carolina, Columbia.

Offering perspective on the study, Taylor C. Wallace, PhD, with the department of nutrition and food studies, George Mason University, Fairfax, Va., made the point that “food processing and ultraprocessed foods aren’t the problem. The problem is the types of ultraprocessed foods on the market that people consume.”

“Remember, non-fat, vitamin D fortified yogurt is also ‘ultra-processed,’ and it’s very healthy,” he told this news organization.

Dr. Wallace said that it’s no surprise that teens increased their intake of UPFs during the pandemic.

“Of course, people increased processed food intake during the pandemic. Processed foods are shelf stable at a time when grocery stores were running out of things and supply chains weren’t able to keep up. Also, many were depressed and use food to indulge,” he noted.

The study had no funding. Ms. Balhara has no relevant disclosures. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and an advisory board member with Forbes Health.

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

Certain ultraprocessed foods – especially candy, prepackaged pastries, and frozen desserts – could be “gateway foods” for adolescents, leading them to increase their intake of other unhealthy foods, a new study suggests.

“For teens, gateway ultraprocessed foods (candy, store pastries, frozen desserts) should be prioritized for preventive dietary interventions as they increase intake across all other UPFs,” lead researcher Maria Balhara said in an interview.

“The good news,” said Ms. Balhara, is that even small changes, such as reducing how often gateway foods are consumed, may reduce overall intake of unhealthy foods and have a “big impact” on overall health.

Ms. Balhara has a unique perspective on adolescent eating habits: She’s 16 years old, from Florida, and conducted the study while dual-enrolled at Broward College and Cooper City High School.

Her study was released Sept. 7 ahead of presentation at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
 

Blame the pandemic?

Over the past 30 years, there’s been a steady increase in consumption of UPFs worldwide, coupled with mounting evidence that diets rich in UPFs raise the risk for several chronic diseases, including weight gain, hypertension, and increased risk for heart disease and premature death.

For her research, Ms. Balhara asked 315 teenagers (42% male) from 12 high schools in South Florida how often they consumed UPFs over two time periods – before COVID in 2019 and after COVID restrictions were eased in 2022 – using a survey that she developed called the Processed Intake Evaluation (PIE).

More than 2 in 5 teens (43%) increased their consumption of UPFs between 2019 and 2022.

During this time, increased consumption of frozen desserts was associated with an 11% increase in consumption of all other UPFs, whereas increased consumption of prepackaged pastries and candy was associated with a 12% and 31%, respectively, increase in consumption of all other UPFs, Ms. Balhara found.

Encouragingly, 57% of teens decreased their consumption of UPFs between 2019 and 2022.

During this time, decreased consumption of processed meats was associated with an 8% decrease in consumption of all other UPFs, whereas decreased consumption of white bread and biscuits was associated with a 9% and 10%, respectively, decrease in consumption of all other UPFs.

The results provide initial evidence for a new “gateway food model,” Ms. Balhara told this news organization, in which certain UPFs, when increased, drive overall consumption of all UPFs among teens.

Limitations of the study include the self-reported dietary data and the fact that the PIE survey has not been validated.
 

Not all UPFs are bad

“I commend Ms. Balhara for her project, which highlights the importance of establishing good dietary patterns early in life,” Donna K. Arnett, PhD, past president of the AHA, said in a news release.

“The relationship between poor dietary quality and cardiovascular risk factors is well-established. While this is a small, preliminary study, it’s an important topic to continue to investigate and help us understand ways we can influence dietary behaviors to promote optimal cardiovascular health for all ages,” said Dr. Arnett, executive vice president for academic affairs and provost at the University of South Carolina, Columbia.

Offering perspective on the study, Taylor C. Wallace, PhD, with the department of nutrition and food studies, George Mason University, Fairfax, Va., made the point that “food processing and ultraprocessed foods aren’t the problem. The problem is the types of ultraprocessed foods on the market that people consume.”

“Remember, non-fat, vitamin D fortified yogurt is also ‘ultra-processed,’ and it’s very healthy,” he told this news organization.

Dr. Wallace said that it’s no surprise that teens increased their intake of UPFs during the pandemic.

“Of course, people increased processed food intake during the pandemic. Processed foods are shelf stable at a time when grocery stores were running out of things and supply chains weren’t able to keep up. Also, many were depressed and use food to indulge,” he noted.

The study had no funding. Ms. Balhara has no relevant disclosures. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and an advisory board member with Forbes Health.

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

GHENT, BELGIUM – Patients with nonradiographic or radiographic axial spondyloarthritis (axSpA) experienced clinically relevant treatment responses to bimekizumab (Bimzelx) at similar rates that significantly exceeded placebo, regardless of prior experience with a tumor necrosis factor (TNF) inhibitor, according to results from two phase 3 trials presented at the 13th International Congress on Spondyloarthritides.

In addition, around half of patients with either nonradiographic or radiographic disease achieved complete remission of enthesitis by week 16 of treatment with bimekizumab. The drug, a humanized, monoclonal antibody dually inhibiting interleukins (IL) 17A and 17F, is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

Becky McCall/MDedge News

“Bimekizumab blockade works independently of axial spondyloarthritis pretreatment, which means this drug specifically blocks something that other drugs do not reach,” said Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany). He presented 24-week data on the use of bimekizumab.

The BE MOBILE 1 trial involved 256 patients with nonradiographic axSpA, whereas BE MOBILE 2 involved 232 patients with radiographic axSpA. In both trials, bimekizumab 160 mg was administered subcutaneously every 4 weeks, and at week 16, all patients, including those who had received placebo, received open-label bimekizumab for another 8 weeks. This news organization previously reported results from BE MOBILE 2 that were presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 annual meeting.

In Ghent, referring to the nonradiographic patients, Dr. Baraliakos said in an interview, “We saw a very clear response to the active drug even after 2 weeks. The curves separated out from placebo. The week 16 primary analysis showed patients on bimekizumab did significantly better, [and there was] a similar response in those who switched to [open-label] bimekizumab after placebo” at week 16.

In patients with nonradiographic disease at week 24, 52.3% on bimekizumab achieved the trial’s primary outcome of 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40), compared with 46.8% of patients who were receiving placebo and then switched to open-label bimekizumab at week 16, the latter rising from 21.4% at week 16. For comparison, 47.7% on bimekizumab achieved ASAS 40 at week 16.

At week 24 in BE MOBILE 2, 53.8% of patients with radiographic disease on continuous bimekizumab met ASAS 40 criteria, as did 56.8% of patients who switched from placebo to open-label bimekizumab, rising from 22.5% with placebo and 44.8% with bimekizumab at week 16.

Audience member Fabian Proft, MD, of Charité Medical University, Berlin, commented on the latest results as well as wider bimekizumab findings, including those relating to psoriasis. “When we compare this to drugs that are already approved and available, we can assume that bimekizumab is equally effective to existing ones,” he said, noting that “there is the additional option in patients with psoriasis, where it seems to be the most effective drug for this indication. If I had a patient with radiographic or nonradiographic axial SpA and who also had significant psoriasis, then bimekizumab would be my choice of treatment.”


 

Targeting IL-17A and IL-17F in one drug

In the BE MOBILE 1 study, Dr. Baraliakos and coinvestigators looked at whether inhibiting IL-17F as well as IL-17A “makes sense” in terms of clinical benefits in patients with axSpA.

“Previous experience with IL-17A inhibitors shows they work well but still miss some patients,” Dr. Baraliakos said, adding that, “the hope is that by blocking both IL-17A and IL-17F, the response will be a bit better in terms of both greater response and longevity of response than [with an] IL-17A [inhibitor] alone.”

Patients in BE MOBILE 1 were typical adult patients with nonradiographic axSpA who fulfilled ASAS classification criteria and had elevated C-reactive protein (CRP) and/or sacroiliitis on MRI. All patients were older than 18 years and had a mean age of 39 years. In each arm, 51%-57% were men. Overall, patients had a mean of 9 years of symptoms and a mean Ankylosing Spondylitis Disease Activity Score of 3.7 in both patient groups (placebo and bimekizumab).

All had active disease (Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 and spi­nal pain ≥ 4) at baseline and demonstrated failure to respond to two different NSAIDs or had a history of intolerance to or contraindication to NSAIDs. Patients had previously received up to one TNF inhibitor (13.5% in the placebo group and 7.8% in the bimekizumab group).

The primary outcome compared rate of response to ASAS 40 criteria, which comprises patient global assessment of disease, spinal pain, function (as assessed by the Bath Ankylosing Spondylitis Functional Index [BASFI]), and inflammation (stiffness).

Early response seen regardless of previous TNF inhibitor experience

“We saw response to bimekizumab very early in our patients at 16 weeks. The amount of response was higher than that observed with IL-17A alone,” Dr. Baraliakos said in an interview. “It’s understood that IL-17A and IL-17F do not work together on the inflammatory cascade, but work separately, and this might explain the findings whereby this drug captures more inflammation.”

Dr. Baraliakos highlighted the unique response rates seen with bimekizumab regardless of past TNF inhibitor use. “The TNF inhibitor-experienced patients responded as well as the TNF inhibitor–naive ones. This is unusual because nonresponders to other drugs are usually more severely affected and have a lower chance of showing response to any drug. Also, we did not see this response in patients treated with IL-17A only.”

At 16 weeks, patients with nonradiographic disease without a past history of using a TNF inhibitor had ASAS 40 responses at rates of 46.6% with bimekizumab and 22.9% with placebo. These rates in patients with past TNF inhibitor use were 60% with bimekizumab and 11.8% with placebo.

Statistically significant differences between bimekizumab and placebo occurred for all primary and secondary outcomes. “This includes the MRI inflammation findings in bimekizumab-treated patients,” Dr. Baraliakos reported.

Complete resolution of enthesitis was also observed. By week 24, enthesitis completely resolved in 47.9% of patients with nonradiographic disease on continuous bimekizumab and 43.5% of those patients who switched from placebo to bimekizumab. In patients with radiographic disease, complete resolution occurred in 53% of those on continuous bimekizumab and 49.3% of patients who switched at week 16. “This was an excellent outcome,” Dr. Baraliakos said.

The safety profile at 24 weeks confirmed prior findings at 16 weeks in which the most common treatment-emergent adverse events with bimekizumab were nasopharyngitis (9.4%), upper respiratory tract infection (7%), and oral candidiasis (3.1%); fungal infections overall occurred in 7% taking bimekizumab.

“We saw slightly higher fungal infections, but this is because we block IL-17A and IL-17F, and [the risk for these infections] is linked to the mechanism of action. But we can deal with this,” Dr. Baraliakos said.

The trials were sponsored by UCB. Dr. Baraliakos disclosed serving on the speakers bureau and as a paid instructor and consultant for Ab­bVie, Bristol-Myers Squibb, Chugai, Eli Lilly, Galapagos, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, and UCB. Dr. Proft disclosed serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; being a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly.

GHENT, BELGIUM – Patients with nonradiographic or radiographic axial spondyloarthritis (axSpA) experienced clinically relevant treatment responses to bimekizumab (Bimzelx) at similar rates that significantly exceeded placebo, regardless of prior experience with a tumor necrosis factor (TNF) inhibitor, according to results from two phase 3 trials presented at the 13th International Congress on Spondyloarthritides.

In addition, around half of patients with either nonradiographic or radiographic disease achieved complete remission of enthesitis by week 16 of treatment with bimekizumab. The drug, a humanized, monoclonal antibody dually inhibiting interleukins (IL) 17A and 17F, is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

Becky McCall/MDedge News

“Bimekizumab blockade works independently of axial spondyloarthritis pretreatment, which means this drug specifically blocks something that other drugs do not reach,” said Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany). He presented 24-week data on the use of bimekizumab.

The BE MOBILE 1 trial involved 256 patients with nonradiographic axSpA, whereas BE MOBILE 2 involved 232 patients with radiographic axSpA. In both trials, bimekizumab 160 mg was administered subcutaneously every 4 weeks, and at week 16, all patients, including those who had received placebo, received open-label bimekizumab for another 8 weeks. This news organization previously reported results from BE MOBILE 2 that were presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 annual meeting.

In Ghent, referring to the nonradiographic patients, Dr. Baraliakos said in an interview, “We saw a very clear response to the active drug even after 2 weeks. The curves separated out from placebo. The week 16 primary analysis showed patients on bimekizumab did significantly better, [and there was] a similar response in those who switched to [open-label] bimekizumab after placebo” at week 16.

In patients with nonradiographic disease at week 24, 52.3% on bimekizumab achieved the trial’s primary outcome of 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40), compared with 46.8% of patients who were receiving placebo and then switched to open-label bimekizumab at week 16, the latter rising from 21.4% at week 16. For comparison, 47.7% on bimekizumab achieved ASAS 40 at week 16.

At week 24 in BE MOBILE 2, 53.8% of patients with radiographic disease on continuous bimekizumab met ASAS 40 criteria, as did 56.8% of patients who switched from placebo to open-label bimekizumab, rising from 22.5% with placebo and 44.8% with bimekizumab at week 16.

Audience member Fabian Proft, MD, of Charité Medical University, Berlin, commented on the latest results as well as wider bimekizumab findings, including those relating to psoriasis. “When we compare this to drugs that are already approved and available, we can assume that bimekizumab is equally effective to existing ones,” he said, noting that “there is the additional option in patients with psoriasis, where it seems to be the most effective drug for this indication. If I had a patient with radiographic or nonradiographic axial SpA and who also had significant psoriasis, then bimekizumab would be my choice of treatment.”


 

Targeting IL-17A and IL-17F in one drug

In the BE MOBILE 1 study, Dr. Baraliakos and coinvestigators looked at whether inhibiting IL-17F as well as IL-17A “makes sense” in terms of clinical benefits in patients with axSpA.

“Previous experience with IL-17A inhibitors shows they work well but still miss some patients,” Dr. Baraliakos said, adding that, “the hope is that by blocking both IL-17A and IL-17F, the response will be a bit better in terms of both greater response and longevity of response than [with an] IL-17A [inhibitor] alone.”

Patients in BE MOBILE 1 were typical adult patients with nonradiographic axSpA who fulfilled ASAS classification criteria and had elevated C-reactive protein (CRP) and/or sacroiliitis on MRI. All patients were older than 18 years and had a mean age of 39 years. In each arm, 51%-57% were men. Overall, patients had a mean of 9 years of symptoms and a mean Ankylosing Spondylitis Disease Activity Score of 3.7 in both patient groups (placebo and bimekizumab).

All had active disease (Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 and spi­nal pain ≥ 4) at baseline and demonstrated failure to respond to two different NSAIDs or had a history of intolerance to or contraindication to NSAIDs. Patients had previously received up to one TNF inhibitor (13.5% in the placebo group and 7.8% in the bimekizumab group).

The primary outcome compared rate of response to ASAS 40 criteria, which comprises patient global assessment of disease, spinal pain, function (as assessed by the Bath Ankylosing Spondylitis Functional Index [BASFI]), and inflammation (stiffness).

Early response seen regardless of previous TNF inhibitor experience

“We saw response to bimekizumab very early in our patients at 16 weeks. The amount of response was higher than that observed with IL-17A alone,” Dr. Baraliakos said in an interview. “It’s understood that IL-17A and IL-17F do not work together on the inflammatory cascade, but work separately, and this might explain the findings whereby this drug captures more inflammation.”

Dr. Baraliakos highlighted the unique response rates seen with bimekizumab regardless of past TNF inhibitor use. “The TNF inhibitor-experienced patients responded as well as the TNF inhibitor–naive ones. This is unusual because nonresponders to other drugs are usually more severely affected and have a lower chance of showing response to any drug. Also, we did not see this response in patients treated with IL-17A only.”

At 16 weeks, patients with nonradiographic disease without a past history of using a TNF inhibitor had ASAS 40 responses at rates of 46.6% with bimekizumab and 22.9% with placebo. These rates in patients with past TNF inhibitor use were 60% with bimekizumab and 11.8% with placebo.

Statistically significant differences between bimekizumab and placebo occurred for all primary and secondary outcomes. “This includes the MRI inflammation findings in bimekizumab-treated patients,” Dr. Baraliakos reported.

Complete resolution of enthesitis was also observed. By week 24, enthesitis completely resolved in 47.9% of patients with nonradiographic disease on continuous bimekizumab and 43.5% of those patients who switched from placebo to bimekizumab. In patients with radiographic disease, complete resolution occurred in 53% of those on continuous bimekizumab and 49.3% of patients who switched at week 16. “This was an excellent outcome,” Dr. Baraliakos said.

The safety profile at 24 weeks confirmed prior findings at 16 weeks in which the most common treatment-emergent adverse events with bimekizumab were nasopharyngitis (9.4%), upper respiratory tract infection (7%), and oral candidiasis (3.1%); fungal infections overall occurred in 7% taking bimekizumab.

“We saw slightly higher fungal infections, but this is because we block IL-17A and IL-17F, and [the risk for these infections] is linked to the mechanism of action. But we can deal with this,” Dr. Baraliakos said.

The trials were sponsored by UCB. Dr. Baraliakos disclosed serving on the speakers bureau and as a paid instructor and consultant for Ab­bVie, Bristol-Myers Squibb, Chugai, Eli Lilly, Galapagos, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, and UCB. Dr. Proft disclosed serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; being a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly.

GHENT, BELGIUM – Patients with nonradiographic or radiographic axial spondyloarthritis (axSpA) experienced clinically relevant treatment responses to bimekizumab (Bimzelx) at similar rates that significantly exceeded placebo, regardless of prior experience with a tumor necrosis factor (TNF) inhibitor, according to results from two phase 3 trials presented at the 13th International Congress on Spondyloarthritides.

In addition, around half of patients with either nonradiographic or radiographic disease achieved complete remission of enthesitis by week 16 of treatment with bimekizumab. The drug, a humanized, monoclonal antibody dually inhibiting interleukins (IL) 17A and 17F, is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

Becky McCall/MDedge News

“Bimekizumab blockade works independently of axial spondyloarthritis pretreatment, which means this drug specifically blocks something that other drugs do not reach,” said Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany). He presented 24-week data on the use of bimekizumab.

The BE MOBILE 1 trial involved 256 patients with nonradiographic axSpA, whereas BE MOBILE 2 involved 232 patients with radiographic axSpA. In both trials, bimekizumab 160 mg was administered subcutaneously every 4 weeks, and at week 16, all patients, including those who had received placebo, received open-label bimekizumab for another 8 weeks. This news organization previously reported results from BE MOBILE 2 that were presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 annual meeting.

In Ghent, referring to the nonradiographic patients, Dr. Baraliakos said in an interview, “We saw a very clear response to the active drug even after 2 weeks. The curves separated out from placebo. The week 16 primary analysis showed patients on bimekizumab did significantly better, [and there was] a similar response in those who switched to [open-label] bimekizumab after placebo” at week 16.

In patients with nonradiographic disease at week 24, 52.3% on bimekizumab achieved the trial’s primary outcome of 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40), compared with 46.8% of patients who were receiving placebo and then switched to open-label bimekizumab at week 16, the latter rising from 21.4% at week 16. For comparison, 47.7% on bimekizumab achieved ASAS 40 at week 16.

At week 24 in BE MOBILE 2, 53.8% of patients with radiographic disease on continuous bimekizumab met ASAS 40 criteria, as did 56.8% of patients who switched from placebo to open-label bimekizumab, rising from 22.5% with placebo and 44.8% with bimekizumab at week 16.

Audience member Fabian Proft, MD, of Charité Medical University, Berlin, commented on the latest results as well as wider bimekizumab findings, including those relating to psoriasis. “When we compare this to drugs that are already approved and available, we can assume that bimekizumab is equally effective to existing ones,” he said, noting that “there is the additional option in patients with psoriasis, where it seems to be the most effective drug for this indication. If I had a patient with radiographic or nonradiographic axial SpA and who also had significant psoriasis, then bimekizumab would be my choice of treatment.”


 

Targeting IL-17A and IL-17F in one drug

In the BE MOBILE 1 study, Dr. Baraliakos and coinvestigators looked at whether inhibiting IL-17F as well as IL-17A “makes sense” in terms of clinical benefits in patients with axSpA.

“Previous experience with IL-17A inhibitors shows they work well but still miss some patients,” Dr. Baraliakos said, adding that, “the hope is that by blocking both IL-17A and IL-17F, the response will be a bit better in terms of both greater response and longevity of response than [with an] IL-17A [inhibitor] alone.”

Patients in BE MOBILE 1 were typical adult patients with nonradiographic axSpA who fulfilled ASAS classification criteria and had elevated C-reactive protein (CRP) and/or sacroiliitis on MRI. All patients were older than 18 years and had a mean age of 39 years. In each arm, 51%-57% were men. Overall, patients had a mean of 9 years of symptoms and a mean Ankylosing Spondylitis Disease Activity Score of 3.7 in both patient groups (placebo and bimekizumab).

All had active disease (Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 and spi­nal pain ≥ 4) at baseline and demonstrated failure to respond to two different NSAIDs or had a history of intolerance to or contraindication to NSAIDs. Patients had previously received up to one TNF inhibitor (13.5% in the placebo group and 7.8% in the bimekizumab group).

The primary outcome compared rate of response to ASAS 40 criteria, which comprises patient global assessment of disease, spinal pain, function (as assessed by the Bath Ankylosing Spondylitis Functional Index [BASFI]), and inflammation (stiffness).

Early response seen regardless of previous TNF inhibitor experience

“We saw response to bimekizumab very early in our patients at 16 weeks. The amount of response was higher than that observed with IL-17A alone,” Dr. Baraliakos said in an interview. “It’s understood that IL-17A and IL-17F do not work together on the inflammatory cascade, but work separately, and this might explain the findings whereby this drug captures more inflammation.”

Dr. Baraliakos highlighted the unique response rates seen with bimekizumab regardless of past TNF inhibitor use. “The TNF inhibitor-experienced patients responded as well as the TNF inhibitor–naive ones. This is unusual because nonresponders to other drugs are usually more severely affected and have a lower chance of showing response to any drug. Also, we did not see this response in patients treated with IL-17A only.”

At 16 weeks, patients with nonradiographic disease without a past history of using a TNF inhibitor had ASAS 40 responses at rates of 46.6% with bimekizumab and 22.9% with placebo. These rates in patients with past TNF inhibitor use were 60% with bimekizumab and 11.8% with placebo.

Statistically significant differences between bimekizumab and placebo occurred for all primary and secondary outcomes. “This includes the MRI inflammation findings in bimekizumab-treated patients,” Dr. Baraliakos reported.

Complete resolution of enthesitis was also observed. By week 24, enthesitis completely resolved in 47.9% of patients with nonradiographic disease on continuous bimekizumab and 43.5% of those patients who switched from placebo to bimekizumab. In patients with radiographic disease, complete resolution occurred in 53% of those on continuous bimekizumab and 49.3% of patients who switched at week 16. “This was an excellent outcome,” Dr. Baraliakos said.

The safety profile at 24 weeks confirmed prior findings at 16 weeks in which the most common treatment-emergent adverse events with bimekizumab were nasopharyngitis (9.4%), upper respiratory tract infection (7%), and oral candidiasis (3.1%); fungal infections overall occurred in 7% taking bimekizumab.

“We saw slightly higher fungal infections, but this is because we block IL-17A and IL-17F, and [the risk for these infections] is linked to the mechanism of action. But we can deal with this,” Dr. Baraliakos said.

The trials were sponsored by UCB. Dr. Baraliakos disclosed serving on the speakers bureau and as a paid instructor and consultant for Ab­bVie, Bristol-Myers Squibb, Chugai, Eli Lilly, Galapagos, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, and UCB. Dr. Proft disclosed serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; being a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly.

The largest-ever independent study into the effects of cannabis on the brain is being carried out in the United Kingdom.

Even though cannabis is the most commonly used illegal drug in the United Kingdom and medicinal cannabis has been legal there since 2018 little is known about why some people react badly to it and others seem to benefit from it.

According to Home Office figures on drug use from 2019, 7.6% of adults aged 16-59 used cannabis in the previous year.

Medicinal cannabis in the United Kingdom can only be prescribed if no other licensed medicine could help the patient. At the moment, GPs can’t prescribe it, only specialist hospital doctors can. The National Health Service says it can only be used in three circumstances: in rare, severe epilepsy; to deal with chemotherapy side effects such as nausea; or to help with multiple sclerosis.

So, with cannabis being used both recreationally and medicinally, King’s College London is carrying out a wide-reaching scientific study into its effect on the human brain.

As part of the Cannabis&Me study, KCL needs to get 3,000 current cannabis users and 3,000 non–cannabis users to take part in an online survey, with a third of those survey respondents then taking part in a face-to-face assessment that includes virtual reality (VR) and psychological analysis. The study also aims to determine how the DNA of cannabis users and their endocannabinoid system impacts their experiences, both negative and positive, with the drug. 

The study is spearheaded by Marta Di Forti, MD, PhD, and has been allocated over £2.5 million in funding by the Medical Research Council. 

This news organization asked Dr. Di Forti about the study.
 

Question: How do you describe the study? 

Answer: “It’s a really unique study. We are aiming to see what’s happening to people using cannabis in the privacy of their homes for medicinal, recreational reasons, or whatever other reason.

“The debate on cannabis has always been quite polarized. There have been people who experience adversities with cannabis use, especially psychosis, whose families may perhaps like cannabis to be abolished if possible. Then there are other people who are saying they get positive benefits from using cannabis.”
 

Q: So where does the study come in?

A: “The study wants to bring the two sides of the argument together and understand what’s really happening. The group I see as a clinician comes to severe harm when they use cannabis regularly. We want to find out who they are and whether we can identify them. While we need to make sure they never come to harm when using cannabis, we need to consider others who won’t come to harm from using cannabis and give them a chance to use it in a way that’s beneficial.”

Q: How does the study work?

A: “The first step of the study is to use an online questionnaire that can be filled in by anyone aged 18-45 who lives in the London area or can travel here if selected. The first set of questions are a general idea of their cannabis use: ‘Why do they use it?’ ‘What are its benefits?’ Then, general questions on what their life has been like up to that point: ‘Did they have any adversities in childhood?’ ‘How is their mood and anxiety levels?’ ‘Do they experience any paranoid responses in everyday life?’ It probably takes between 30 and 40 minutes to fill out the questionnaire.”

Q: Can you explain about paranoid responses?

A: “We go through the questionnaires looking at people’s paranoid response to everyday life, not in a clinical disorder term, just in terms of the differences in how we respond to certain circumstances. For example: ‘How do you feel if someone’s staring at you on the Tube?’ Some people are afraid, some feel uncomfortable, some people don’t notice, and others think a person is staring at them as they look good or another such positive feeling. So, we give people a paranoia score and will invite some at the top and some at the bottom of that score for a face-to-face assessment. We want to select those people who are using cannabis daily and they are getting either no paranoia or high paranoia.”

Q: What happens at the face-to-face assessments?

A: “We do two things which are very novel. We ask them to take part in a virtual reality experience. They are in a lovely shop and within this experience they come across challenges, which may or may not induce a benign paranoia response. We will ask them to donate a sample of blood before they go into the VR set. We will test for tetrahydrocannabinol (THC) and cannabidiol (CBD). We will also look at the metabolites of the two. People don’t take into account how differently individuals metabolize cannabis, which could be one of the reasons why some people can tolerate it and others can’t.”

Q: There’s also a genetic aspect of the study?

A: “From the same sample, we will extract DNA to look at the genetics across the genome and compare genetic variations between high and low paranoia in the context of cannabis use. Also, we will look at the epigenetics, as we have learned from neuroscience, and also cancer, that sometimes a substance we ingest has an effect on our health. It’s perhaps an interaction with the way our DNA is written but also with the changes to the way our DNA is read and translated into biology if exposed to that substance. We know that smoking tobacco does have an impact at an epigenetic level on the DNA. We do know that in people who stop smoking, these impacts on the epigenetics are partially reversed. This work hasn’t been done properly for cannabis.

“There have been four published studies that have looked at the effect of cannabis use on epigenetics but they have been quite inconclusive, and they haven’t looked at large numbers of current users taking into account how much they are using. Moreover, we do know that when THC and CBD get into our bodies, they interact with something that is already embedded in our biology which is the endocannabinoid system. Therefore, in the blood samples we also aim to measures the levels of the endocannabinoids we naturally produce.

“All of this data will then be analyzed to see if we can get close to understanding what makes some cannabis users susceptible to paranoia while others who are using cannabis get some benefits, even in the domain of mental health.”
 

Q: Who are you looking for to take part in your study?

A: “What we don’t want is to get only people who are the classic friends and family of academics to do the study. We want a representative sample of people out there who are using cannabis. My ideal candidate would be someone who hates me and usually sends me abusive emails saying I’m against cannabis, which is wrong. All I want to find out is who is susceptible to harm which will keep everybody else safe. We are not trying to demonize cannabis; it’s exactly the opposite. We would like people from all ethnic and socioeconomic backgrounds to join to give voice to everyone out there using cannabis, the reasons why, and the effects they experience.”

Q: Will this study perhaps give more information of when it’s appropriate to prescribe medicinal cannabis, as it’s still quite unusual for it to be prescribed in the United Kingdom isn’t it?

A: “Absolutely spot on. That’s exactly the point. We want to hear from people who are receiving medicinal cannabis as a prescription, as they are likely to take it on a daily basis and daily use is what epidemiological studies have linked to the highest risk of psychosis. There will be people taking THC everyday for pain, nausea, for Crohn’s disease, and more.

“Normally when you receive a prescription for a medication the physician in charge will tell you the potential side effects which will be monitored to make sure it’s safe, and you may have to swap to a different medication. Now this isn’t really happening with medicinal cannabis, which is one of the reasons clinicians are anxious about prescribing it, and they have been criticized for not prescribing it very much. There’s much less structure and guidance about ‘psychosis-related’ side effects monitoring. If we can really identify those people who are likely to develop psychosis or disabling paranoia when they use cannabis, physicians might be more prepared to prescribe more widely when indicated.

“You could even have a virtual reality scenario available as a screening tool when you get prescribed medicinal cannabis, to see if there are changes in your perception of the world, which is ultimately what psychosis is about. Could this be a way of implementing safe prescribing which will encourage physicians to use safe cannabis compounds and make some people less anxious about it?

“This study is not here to highlight the negativity of cannabis, on the contrary it’s to understand how it can be used recreationally, but even more important, medicinally in a safe way so people that are coming to no harm can continue to do so and people who are at risk can be kept safe, or at least monitored adequately.”

A version of this article first appeared on Medscape UK.

The largest-ever independent study into the effects of cannabis on the brain is being carried out in the United Kingdom.

Even though cannabis is the most commonly used illegal drug in the United Kingdom and medicinal cannabis has been legal there since 2018 little is known about why some people react badly to it and others seem to benefit from it.

According to Home Office figures on drug use from 2019, 7.6% of adults aged 16-59 used cannabis in the previous year.

Medicinal cannabis in the United Kingdom can only be prescribed if no other licensed medicine could help the patient. At the moment, GPs can’t prescribe it, only specialist hospital doctors can. The National Health Service says it can only be used in three circumstances: in rare, severe epilepsy; to deal with chemotherapy side effects such as nausea; or to help with multiple sclerosis.

So, with cannabis being used both recreationally and medicinally, King’s College London is carrying out a wide-reaching scientific study into its effect on the human brain.

As part of the Cannabis&Me study, KCL needs to get 3,000 current cannabis users and 3,000 non–cannabis users to take part in an online survey, with a third of those survey respondents then taking part in a face-to-face assessment that includes virtual reality (VR) and psychological analysis. The study also aims to determine how the DNA of cannabis users and their endocannabinoid system impacts their experiences, both negative and positive, with the drug. 

The study is spearheaded by Marta Di Forti, MD, PhD, and has been allocated over £2.5 million in funding by the Medical Research Council. 

This news organization asked Dr. Di Forti about the study.
 

Question: How do you describe the study? 

Answer: “It’s a really unique study. We are aiming to see what’s happening to people using cannabis in the privacy of their homes for medicinal, recreational reasons, or whatever other reason.

“The debate on cannabis has always been quite polarized. There have been people who experience adversities with cannabis use, especially psychosis, whose families may perhaps like cannabis to be abolished if possible. Then there are other people who are saying they get positive benefits from using cannabis.”
 

Q: So where does the study come in?

A: “The study wants to bring the two sides of the argument together and understand what’s really happening. The group I see as a clinician comes to severe harm when they use cannabis regularly. We want to find out who they are and whether we can identify them. While we need to make sure they never come to harm when using cannabis, we need to consider others who won’t come to harm from using cannabis and give them a chance to use it in a way that’s beneficial.”

Q: How does the study work?

A: “The first step of the study is to use an online questionnaire that can be filled in by anyone aged 18-45 who lives in the London area or can travel here if selected. The first set of questions are a general idea of their cannabis use: ‘Why do they use it?’ ‘What are its benefits?’ Then, general questions on what their life has been like up to that point: ‘Did they have any adversities in childhood?’ ‘How is their mood and anxiety levels?’ ‘Do they experience any paranoid responses in everyday life?’ It probably takes between 30 and 40 minutes to fill out the questionnaire.”

Q: Can you explain about paranoid responses?

A: “We go through the questionnaires looking at people’s paranoid response to everyday life, not in a clinical disorder term, just in terms of the differences in how we respond to certain circumstances. For example: ‘How do you feel if someone’s staring at you on the Tube?’ Some people are afraid, some feel uncomfortable, some people don’t notice, and others think a person is staring at them as they look good or another such positive feeling. So, we give people a paranoia score and will invite some at the top and some at the bottom of that score for a face-to-face assessment. We want to select those people who are using cannabis daily and they are getting either no paranoia or high paranoia.”

Q: What happens at the face-to-face assessments?

A: “We do two things which are very novel. We ask them to take part in a virtual reality experience. They are in a lovely shop and within this experience they come across challenges, which may or may not induce a benign paranoia response. We will ask them to donate a sample of blood before they go into the VR set. We will test for tetrahydrocannabinol (THC) and cannabidiol (CBD). We will also look at the metabolites of the two. People don’t take into account how differently individuals metabolize cannabis, which could be one of the reasons why some people can tolerate it and others can’t.”

Q: There’s also a genetic aspect of the study?

A: “From the same sample, we will extract DNA to look at the genetics across the genome and compare genetic variations between high and low paranoia in the context of cannabis use. Also, we will look at the epigenetics, as we have learned from neuroscience, and also cancer, that sometimes a substance we ingest has an effect on our health. It’s perhaps an interaction with the way our DNA is written but also with the changes to the way our DNA is read and translated into biology if exposed to that substance. We know that smoking tobacco does have an impact at an epigenetic level on the DNA. We do know that in people who stop smoking, these impacts on the epigenetics are partially reversed. This work hasn’t been done properly for cannabis.

“There have been four published studies that have looked at the effect of cannabis use on epigenetics but they have been quite inconclusive, and they haven’t looked at large numbers of current users taking into account how much they are using. Moreover, we do know that when THC and CBD get into our bodies, they interact with something that is already embedded in our biology which is the endocannabinoid system. Therefore, in the blood samples we also aim to measures the levels of the endocannabinoids we naturally produce.

“All of this data will then be analyzed to see if we can get close to understanding what makes some cannabis users susceptible to paranoia while others who are using cannabis get some benefits, even in the domain of mental health.”
 

Q: Who are you looking for to take part in your study?

A: “What we don’t want is to get only people who are the classic friends and family of academics to do the study. We want a representative sample of people out there who are using cannabis. My ideal candidate would be someone who hates me and usually sends me abusive emails saying I’m against cannabis, which is wrong. All I want to find out is who is susceptible to harm which will keep everybody else safe. We are not trying to demonize cannabis; it’s exactly the opposite. We would like people from all ethnic and socioeconomic backgrounds to join to give voice to everyone out there using cannabis, the reasons why, and the effects they experience.”

Q: Will this study perhaps give more information of when it’s appropriate to prescribe medicinal cannabis, as it’s still quite unusual for it to be prescribed in the United Kingdom isn’t it?

A: “Absolutely spot on. That’s exactly the point. We want to hear from people who are receiving medicinal cannabis as a prescription, as they are likely to take it on a daily basis and daily use is what epidemiological studies have linked to the highest risk of psychosis. There will be people taking THC everyday for pain, nausea, for Crohn’s disease, and more.

“Normally when you receive a prescription for a medication the physician in charge will tell you the potential side effects which will be monitored to make sure it’s safe, and you may have to swap to a different medication. Now this isn’t really happening with medicinal cannabis, which is one of the reasons clinicians are anxious about prescribing it, and they have been criticized for not prescribing it very much. There’s much less structure and guidance about ‘psychosis-related’ side effects monitoring. If we can really identify those people who are likely to develop psychosis or disabling paranoia when they use cannabis, physicians might be more prepared to prescribe more widely when indicated.

“You could even have a virtual reality scenario available as a screening tool when you get prescribed medicinal cannabis, to see if there are changes in your perception of the world, which is ultimately what psychosis is about. Could this be a way of implementing safe prescribing which will encourage physicians to use safe cannabis compounds and make some people less anxious about it?

“This study is not here to highlight the negativity of cannabis, on the contrary it’s to understand how it can be used recreationally, but even more important, medicinally in a safe way so people that are coming to no harm can continue to do so and people who are at risk can be kept safe, or at least monitored adequately.”

A version of this article first appeared on Medscape UK.

The largest-ever independent study into the effects of cannabis on the brain is being carried out in the United Kingdom.

Even though cannabis is the most commonly used illegal drug in the United Kingdom and medicinal cannabis has been legal there since 2018 little is known about why some people react badly to it and others seem to benefit from it.

According to Home Office figures on drug use from 2019, 7.6% of adults aged 16-59 used cannabis in the previous year.

Medicinal cannabis in the United Kingdom can only be prescribed if no other licensed medicine could help the patient. At the moment, GPs can’t prescribe it, only specialist hospital doctors can. The National Health Service says it can only be used in three circumstances: in rare, severe epilepsy; to deal with chemotherapy side effects such as nausea; or to help with multiple sclerosis.

So, with cannabis being used both recreationally and medicinally, King’s College London is carrying out a wide-reaching scientific study into its effect on the human brain.

As part of the Cannabis&Me study, KCL needs to get 3,000 current cannabis users and 3,000 non–cannabis users to take part in an online survey, with a third of those survey respondents then taking part in a face-to-face assessment that includes virtual reality (VR) and psychological analysis. The study also aims to determine how the DNA of cannabis users and their endocannabinoid system impacts their experiences, both negative and positive, with the drug. 

The study is spearheaded by Marta Di Forti, MD, PhD, and has been allocated over £2.5 million in funding by the Medical Research Council. 

This news organization asked Dr. Di Forti about the study.
 

Question: How do you describe the study? 

Answer: “It’s a really unique study. We are aiming to see what’s happening to people using cannabis in the privacy of their homes for medicinal, recreational reasons, or whatever other reason.

“The debate on cannabis has always been quite polarized. There have been people who experience adversities with cannabis use, especially psychosis, whose families may perhaps like cannabis to be abolished if possible. Then there are other people who are saying they get positive benefits from using cannabis.”
 

Q: So where does the study come in?

A: “The study wants to bring the two sides of the argument together and understand what’s really happening. The group I see as a clinician comes to severe harm when they use cannabis regularly. We want to find out who they are and whether we can identify them. While we need to make sure they never come to harm when using cannabis, we need to consider others who won’t come to harm from using cannabis and give them a chance to use it in a way that’s beneficial.”

Q: How does the study work?

A: “The first step of the study is to use an online questionnaire that can be filled in by anyone aged 18-45 who lives in the London area or can travel here if selected. The first set of questions are a general idea of their cannabis use: ‘Why do they use it?’ ‘What are its benefits?’ Then, general questions on what their life has been like up to that point: ‘Did they have any adversities in childhood?’ ‘How is their mood and anxiety levels?’ ‘Do they experience any paranoid responses in everyday life?’ It probably takes between 30 and 40 minutes to fill out the questionnaire.”

Q: Can you explain about paranoid responses?

A: “We go through the questionnaires looking at people’s paranoid response to everyday life, not in a clinical disorder term, just in terms of the differences in how we respond to certain circumstances. For example: ‘How do you feel if someone’s staring at you on the Tube?’ Some people are afraid, some feel uncomfortable, some people don’t notice, and others think a person is staring at them as they look good or another such positive feeling. So, we give people a paranoia score and will invite some at the top and some at the bottom of that score for a face-to-face assessment. We want to select those people who are using cannabis daily and they are getting either no paranoia or high paranoia.”

Q: What happens at the face-to-face assessments?

A: “We do two things which are very novel. We ask them to take part in a virtual reality experience. They are in a lovely shop and within this experience they come across challenges, which may or may not induce a benign paranoia response. We will ask them to donate a sample of blood before they go into the VR set. We will test for tetrahydrocannabinol (THC) and cannabidiol (CBD). We will also look at the metabolites of the two. People don’t take into account how differently individuals metabolize cannabis, which could be one of the reasons why some people can tolerate it and others can’t.”

Q: There’s also a genetic aspect of the study?

A: “From the same sample, we will extract DNA to look at the genetics across the genome and compare genetic variations between high and low paranoia in the context of cannabis use. Also, we will look at the epigenetics, as we have learned from neuroscience, and also cancer, that sometimes a substance we ingest has an effect on our health. It’s perhaps an interaction with the way our DNA is written but also with the changes to the way our DNA is read and translated into biology if exposed to that substance. We know that smoking tobacco does have an impact at an epigenetic level on the DNA. We do know that in people who stop smoking, these impacts on the epigenetics are partially reversed. This work hasn’t been done properly for cannabis.

“There have been four published studies that have looked at the effect of cannabis use on epigenetics but they have been quite inconclusive, and they haven’t looked at large numbers of current users taking into account how much they are using. Moreover, we do know that when THC and CBD get into our bodies, they interact with something that is already embedded in our biology which is the endocannabinoid system. Therefore, in the blood samples we also aim to measures the levels of the endocannabinoids we naturally produce.

“All of this data will then be analyzed to see if we can get close to understanding what makes some cannabis users susceptible to paranoia while others who are using cannabis get some benefits, even in the domain of mental health.”
 

Q: Who are you looking for to take part in your study?

A: “What we don’t want is to get only people who are the classic friends and family of academics to do the study. We want a representative sample of people out there who are using cannabis. My ideal candidate would be someone who hates me and usually sends me abusive emails saying I’m against cannabis, which is wrong. All I want to find out is who is susceptible to harm which will keep everybody else safe. We are not trying to demonize cannabis; it’s exactly the opposite. We would like people from all ethnic and socioeconomic backgrounds to join to give voice to everyone out there using cannabis, the reasons why, and the effects they experience.”

Q: Will this study perhaps give more information of when it’s appropriate to prescribe medicinal cannabis, as it’s still quite unusual for it to be prescribed in the United Kingdom isn’t it?

A: “Absolutely spot on. That’s exactly the point. We want to hear from people who are receiving medicinal cannabis as a prescription, as they are likely to take it on a daily basis and daily use is what epidemiological studies have linked to the highest risk of psychosis. There will be people taking THC everyday for pain, nausea, for Crohn’s disease, and more.

“Normally when you receive a prescription for a medication the physician in charge will tell you the potential side effects which will be monitored to make sure it’s safe, and you may have to swap to a different medication. Now this isn’t really happening with medicinal cannabis, which is one of the reasons clinicians are anxious about prescribing it, and they have been criticized for not prescribing it very much. There’s much less structure and guidance about ‘psychosis-related’ side effects monitoring. If we can really identify those people who are likely to develop psychosis or disabling paranoia when they use cannabis, physicians might be more prepared to prescribe more widely when indicated.

“You could even have a virtual reality scenario available as a screening tool when you get prescribed medicinal cannabis, to see if there are changes in your perception of the world, which is ultimately what psychosis is about. Could this be a way of implementing safe prescribing which will encourage physicians to use safe cannabis compounds and make some people less anxious about it?

“This study is not here to highlight the negativity of cannabis, on the contrary it’s to understand how it can be used recreationally, but even more important, medicinally in a safe way so people that are coming to no harm can continue to do so and people who are at risk can be kept safe, or at least monitored adequately.”

A version of this article first appeared on Medscape UK.