Clinician Reviews

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

Recent headlines scream that we have an obesity problem and that carbs are the culprit for the problem. That leads me to ask: How did we get to blaming carbs as the enemy in the war against obesity?

First, a quick review of the history of diet and macronutrient content.

A long time ago, prehistoric humans foraged and hunted for food. Protein and fat were procured from animal meat, which was very important for encephalization, or evolutionary increase in the complexity or relative size of the brain. Most of the requirements for protein and iron were satisfied by hunting and eating land animals as well as consuming marine life that washed up on shore.

Carbohydrates in the form of plant foods served as the only sources of energy available to prehistoric hunter-gatherers, which offset the high protein content of the rest of their diet. These were only available during spring and summer.

Then, about 10,000 years ago, plant and animal agriculture began, and humans saw a permanent shift in the macronutrient content of our daily intake so that it was more consistent and stable. Initially, the nutrient characteristic changes were subtle, going from wild food to cultivated food with the Agricultural Revolution in the mid-17th century. Then, it changed even more rapidly less than 200 years ago with the Industrial Revolution, resulting in semiprocessed and ultraprocessed foods.

This change in food intake altered human physiology, with major changes in our digestive, immune, and neural physiology and an increase in chronic disease prevalence. The last 50 years has seen an increase in obesity in the United States, along with increases in chronic disease such as type 2 diabetes, which leads cardiovascular disease and certain cancers. 
 

Back to Carbohydrates: Do We Need Them? How Much? What Kind?

The increase in the macronutrient content of the food we eat containing saturated fat and refined carbohydrates and sugars represents a major change and is arguably the smoking gun of the obesity epidemic. Unfortunately, ultraprocessed foods have become a staple of the standard American or Western diet. 

Ultraprocessed foods such as cakes, cookies, crackers, sugary breakfast cereals, pizza, potato chips, soft drinks, and ice cream are eons away from our prehistoric diet of wild game, nuts, fruits, and berries, at which time, our digestive immune and nervous systems evolved. The pace at which ultraprocessed foods have entered our diet outpaces the time necessary for adaptation of our digestive systems and genes to these foods. They are indeed pathogenic in this context. 

So when was the time when humans consumed an “optimal” diet? This is hard to say because during the time of brain evolution, we needed protein and iron and succumbed to infections and trauma. In the early 1900s, we continued to succumb to infection until the discovery of antibiotics. Soon thereafter, industrialization and processed foods led to weight gain and the chronic diseases of the cardiovascular system and type 2 diabetes. 

Carbohydrates provide calories and fiber and some micronutrients, which are needed for energy, metabolism, and bowel and immune health. But how much do we need? 

Currently in the United States, the percentage of total food energy derived from the three major macronutrients is: carbohydrates, 51.8%; fat, 32.8%; and protein, 15.4%. Current advice for a healthy diet to lower risk for cardiovascular disease is to limit fat intake to 30% of total energy, protein to 15%, and to increase complex carbohydrates to 55%-60% of total energy. But we also need to qualify this in terms of the quality of the macronutrient, particularly carbohydrates. 

In addition to the quality, the macronutrient content of the diet has varied considerably from our prehistoric times when dietary protein intakes were high at 19%-35% of energy at the expense of carbohydrate (22%-40% of energy). 

If our genes haven’t kept up with industrialization, then why do we need so many carbohydrates to equate to 55%-60% of energy? Is it possible that we are confusing what is available with what we actually need? What do I mean by this?

We certainly have changed the landscape of the world due to agriculture, which has allowed us to procreate and feed ourselves, and certainly, industrialization has increased the availability of accessible cheap food. Protein in the form of meat, fish, and fowl are harder to get in industrialized nations as are fruits and vegetables. These macronutrients were the foods of our ancestors. It may be that a healthy diet is considered the one that is available. 

For instance, the Mediterranean diet is somewhat higher in fat content, 40%-50% fat (mostly mono and unsaturated), and similar in protein content but lower in carbohydrate content than the typical Western diet. The Dietary Approaches to Stop Hypertension (DASH) diet is lower in fat at 25% total calories, is higher in carbohydrates at 55%, and is lower in protein, but this diet was generated in the United States, therefore it is more Western. 

We need high-quality protein for organ and muscle function, high-quality unsaturated and monounsaturated fats for brain function and cellular functions, and high-quality complex carbohydrates for energy and gut health as well as micronutrients for many cellular functions. A ketogenic diet is not sustainable in the long-term for these reasons: chiefly the need for some carbohydrates for gut health and micronutrients. 

How much carbohydrate content is needed should take into consideration energy expenditure as well as micronutrients and fiber intake. Protein and fat can contribute to energy production but not as readily as carbohydrates that can quickly restore glycogen in the muscle and liver. What’s interesting is that our ancestors were able to hunt and run away from danger with the small amounts of carbohydrates from plants and berries plus the protein and fat intake from animals and fish — but the Olympics weren’t a thing then!

It may be another 200,000 years before our genes catch up to ultraprocessed foods and the simple carbohydrates and sugars contained in these products. Evidence suggests that ultraprocessed foods cause inflammation in organs like the liver, adipose tissue, the heart, and even the brain. In the brain, this inflammation may be what’s causing us to defend a higher body weight set point in this environment of easily obtained highly palatable ultraprocessed foods. 

Let’s not wait until our genes catch up and our bodies tolerate junk food without disease progression. It could be like waiting for Godot!

Dr. Apovian is professor of medicine, Harvard Medical School, and codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, Massachusetts. She disclosed ties to Altimmune, CinFina Pharma, Cowen and Company, EPG Communication Holdings, Form Health, Gelesis, and L-Nutra.

A version of this article appeared on Medscape.com.

Recent headlines scream that we have an obesity problem and that carbs are the culprit for the problem. That leads me to ask: How did we get to blaming carbs as the enemy in the war against obesity?

First, a quick review of the history of diet and macronutrient content.

A long time ago, prehistoric humans foraged and hunted for food. Protein and fat were procured from animal meat, which was very important for encephalization, or evolutionary increase in the complexity or relative size of the brain. Most of the requirements for protein and iron were satisfied by hunting and eating land animals as well as consuming marine life that washed up on shore.

Carbohydrates in the form of plant foods served as the only sources of energy available to prehistoric hunter-gatherers, which offset the high protein content of the rest of their diet. These were only available during spring and summer.

Then, about 10,000 years ago, plant and animal agriculture began, and humans saw a permanent shift in the macronutrient content of our daily intake so that it was more consistent and stable. Initially, the nutrient characteristic changes were subtle, going from wild food to cultivated food with the Agricultural Revolution in the mid-17th century. Then, it changed even more rapidly less than 200 years ago with the Industrial Revolution, resulting in semiprocessed and ultraprocessed foods.

This change in food intake altered human physiology, with major changes in our digestive, immune, and neural physiology and an increase in chronic disease prevalence. The last 50 years has seen an increase in obesity in the United States, along with increases in chronic disease such as type 2 diabetes, which leads cardiovascular disease and certain cancers. 
 

Back to Carbohydrates: Do We Need Them? How Much? What Kind?

The increase in the macronutrient content of the food we eat containing saturated fat and refined carbohydrates and sugars represents a major change and is arguably the smoking gun of the obesity epidemic. Unfortunately, ultraprocessed foods have become a staple of the standard American or Western diet. 

Ultraprocessed foods such as cakes, cookies, crackers, sugary breakfast cereals, pizza, potato chips, soft drinks, and ice cream are eons away from our prehistoric diet of wild game, nuts, fruits, and berries, at which time, our digestive immune and nervous systems evolved. The pace at which ultraprocessed foods have entered our diet outpaces the time necessary for adaptation of our digestive systems and genes to these foods. They are indeed pathogenic in this context. 

So when was the time when humans consumed an “optimal” diet? This is hard to say because during the time of brain evolution, we needed protein and iron and succumbed to infections and trauma. In the early 1900s, we continued to succumb to infection until the discovery of antibiotics. Soon thereafter, industrialization and processed foods led to weight gain and the chronic diseases of the cardiovascular system and type 2 diabetes. 

Carbohydrates provide calories and fiber and some micronutrients, which are needed for energy, metabolism, and bowel and immune health. But how much do we need? 

Currently in the United States, the percentage of total food energy derived from the three major macronutrients is: carbohydrates, 51.8%; fat, 32.8%; and protein, 15.4%. Current advice for a healthy diet to lower risk for cardiovascular disease is to limit fat intake to 30% of total energy, protein to 15%, and to increase complex carbohydrates to 55%-60% of total energy. But we also need to qualify this in terms of the quality of the macronutrient, particularly carbohydrates. 

In addition to the quality, the macronutrient content of the diet has varied considerably from our prehistoric times when dietary protein intakes were high at 19%-35% of energy at the expense of carbohydrate (22%-40% of energy). 

If our genes haven’t kept up with industrialization, then why do we need so many carbohydrates to equate to 55%-60% of energy? Is it possible that we are confusing what is available with what we actually need? What do I mean by this?

We certainly have changed the landscape of the world due to agriculture, which has allowed us to procreate and feed ourselves, and certainly, industrialization has increased the availability of accessible cheap food. Protein in the form of meat, fish, and fowl are harder to get in industrialized nations as are fruits and vegetables. These macronutrients were the foods of our ancestors. It may be that a healthy diet is considered the one that is available. 

For instance, the Mediterranean diet is somewhat higher in fat content, 40%-50% fat (mostly mono and unsaturated), and similar in protein content but lower in carbohydrate content than the typical Western diet. The Dietary Approaches to Stop Hypertension (DASH) diet is lower in fat at 25% total calories, is higher in carbohydrates at 55%, and is lower in protein, but this diet was generated in the United States, therefore it is more Western. 

We need high-quality protein for organ and muscle function, high-quality unsaturated and monounsaturated fats for brain function and cellular functions, and high-quality complex carbohydrates for energy and gut health as well as micronutrients for many cellular functions. A ketogenic diet is not sustainable in the long-term for these reasons: chiefly the need for some carbohydrates for gut health and micronutrients. 

How much carbohydrate content is needed should take into consideration energy expenditure as well as micronutrients and fiber intake. Protein and fat can contribute to energy production but not as readily as carbohydrates that can quickly restore glycogen in the muscle and liver. What’s interesting is that our ancestors were able to hunt and run away from danger with the small amounts of carbohydrates from plants and berries plus the protein and fat intake from animals and fish — but the Olympics weren’t a thing then!

It may be another 200,000 years before our genes catch up to ultraprocessed foods and the simple carbohydrates and sugars contained in these products. Evidence suggests that ultraprocessed foods cause inflammation in organs like the liver, adipose tissue, the heart, and even the brain. In the brain, this inflammation may be what’s causing us to defend a higher body weight set point in this environment of easily obtained highly palatable ultraprocessed foods. 

Let’s not wait until our genes catch up and our bodies tolerate junk food without disease progression. It could be like waiting for Godot!

Dr. Apovian is professor of medicine, Harvard Medical School, and codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, Massachusetts. She disclosed ties to Altimmune, CinFina Pharma, Cowen and Company, EPG Communication Holdings, Form Health, Gelesis, and L-Nutra.

A version of this article appeared on Medscape.com.

Recent headlines scream that we have an obesity problem and that carbs are the culprit for the problem. That leads me to ask: How did we get to blaming carbs as the enemy in the war against obesity?

First, a quick review of the history of diet and macronutrient content.

A long time ago, prehistoric humans foraged and hunted for food. Protein and fat were procured from animal meat, which was very important for encephalization, or evolutionary increase in the complexity or relative size of the brain. Most of the requirements for protein and iron were satisfied by hunting and eating land animals as well as consuming marine life that washed up on shore.

Carbohydrates in the form of plant foods served as the only sources of energy available to prehistoric hunter-gatherers, which offset the high protein content of the rest of their diet. These were only available during spring and summer.

Then, about 10,000 years ago, plant and animal agriculture began, and humans saw a permanent shift in the macronutrient content of our daily intake so that it was more consistent and stable. Initially, the nutrient characteristic changes were subtle, going from wild food to cultivated food with the Agricultural Revolution in the mid-17th century. Then, it changed even more rapidly less than 200 years ago with the Industrial Revolution, resulting in semiprocessed and ultraprocessed foods.

This change in food intake altered human physiology, with major changes in our digestive, immune, and neural physiology and an increase in chronic disease prevalence. The last 50 years has seen an increase in obesity in the United States, along with increases in chronic disease such as type 2 diabetes, which leads cardiovascular disease and certain cancers. 
 

Back to Carbohydrates: Do We Need Them? How Much? What Kind?

The increase in the macronutrient content of the food we eat containing saturated fat and refined carbohydrates and sugars represents a major change and is arguably the smoking gun of the obesity epidemic. Unfortunately, ultraprocessed foods have become a staple of the standard American or Western diet. 

Ultraprocessed foods such as cakes, cookies, crackers, sugary breakfast cereals, pizza, potato chips, soft drinks, and ice cream are eons away from our prehistoric diet of wild game, nuts, fruits, and berries, at which time, our digestive immune and nervous systems evolved. The pace at which ultraprocessed foods have entered our diet outpaces the time necessary for adaptation of our digestive systems and genes to these foods. They are indeed pathogenic in this context. 

So when was the time when humans consumed an “optimal” diet? This is hard to say because during the time of brain evolution, we needed protein and iron and succumbed to infections and trauma. In the early 1900s, we continued to succumb to infection until the discovery of antibiotics. Soon thereafter, industrialization and processed foods led to weight gain and the chronic diseases of the cardiovascular system and type 2 diabetes. 

Carbohydrates provide calories and fiber and some micronutrients, which are needed for energy, metabolism, and bowel and immune health. But how much do we need? 

Currently in the United States, the percentage of total food energy derived from the three major macronutrients is: carbohydrates, 51.8%; fat, 32.8%; and protein, 15.4%. Current advice for a healthy diet to lower risk for cardiovascular disease is to limit fat intake to 30% of total energy, protein to 15%, and to increase complex carbohydrates to 55%-60% of total energy. But we also need to qualify this in terms of the quality of the macronutrient, particularly carbohydrates. 

In addition to the quality, the macronutrient content of the diet has varied considerably from our prehistoric times when dietary protein intakes were high at 19%-35% of energy at the expense of carbohydrate (22%-40% of energy). 

If our genes haven’t kept up with industrialization, then why do we need so many carbohydrates to equate to 55%-60% of energy? Is it possible that we are confusing what is available with what we actually need? What do I mean by this?

We certainly have changed the landscape of the world due to agriculture, which has allowed us to procreate and feed ourselves, and certainly, industrialization has increased the availability of accessible cheap food. Protein in the form of meat, fish, and fowl are harder to get in industrialized nations as are fruits and vegetables. These macronutrients were the foods of our ancestors. It may be that a healthy diet is considered the one that is available. 

For instance, the Mediterranean diet is somewhat higher in fat content, 40%-50% fat (mostly mono and unsaturated), and similar in protein content but lower in carbohydrate content than the typical Western diet. The Dietary Approaches to Stop Hypertension (DASH) diet is lower in fat at 25% total calories, is higher in carbohydrates at 55%, and is lower in protein, but this diet was generated in the United States, therefore it is more Western. 

We need high-quality protein for organ and muscle function, high-quality unsaturated and monounsaturated fats for brain function and cellular functions, and high-quality complex carbohydrates for energy and gut health as well as micronutrients for many cellular functions. A ketogenic diet is not sustainable in the long-term for these reasons: chiefly the need for some carbohydrates for gut health and micronutrients. 

How much carbohydrate content is needed should take into consideration energy expenditure as well as micronutrients and fiber intake. Protein and fat can contribute to energy production but not as readily as carbohydrates that can quickly restore glycogen in the muscle and liver. What’s interesting is that our ancestors were able to hunt and run away from danger with the small amounts of carbohydrates from plants and berries plus the protein and fat intake from animals and fish — but the Olympics weren’t a thing then!

It may be another 200,000 years before our genes catch up to ultraprocessed foods and the simple carbohydrates and sugars contained in these products. Evidence suggests that ultraprocessed foods cause inflammation in organs like the liver, adipose tissue, the heart, and even the brain. In the brain, this inflammation may be what’s causing us to defend a higher body weight set point in this environment of easily obtained highly palatable ultraprocessed foods. 

Let’s not wait until our genes catch up and our bodies tolerate junk food without disease progression. It could be like waiting for Godot!

Dr. Apovian is professor of medicine, Harvard Medical School, and codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, Massachusetts. She disclosed ties to Altimmune, CinFina Pharma, Cowen and Company, EPG Communication Holdings, Form Health, Gelesis, and L-Nutra.

A version of this article appeared on Medscape.com.

LONDON — Weight loss, glycemic control, fatty liver, and the need for insulin all showed improvement in patients with both refractory type 2 diabetes and obesity after a gut liner known as EndoBarrier (RESET, Morphic Medical, United States) was implanted for 1 year, showed data.

Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.

Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.

“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.

Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
 

Convenient, Reversible Procedure

Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.

Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.

The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.

“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.

Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
 

Over Half Maintained Full Improvement 2 Years Post Removal

A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m², and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.

Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.

Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m², A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.

Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).

Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.

Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.

Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.

Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”

Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.

EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m².
 

A version of this article appeared on Medscape.com.

LONDON — Weight loss, glycemic control, fatty liver, and the need for insulin all showed improvement in patients with both refractory type 2 diabetes and obesity after a gut liner known as EndoBarrier (RESET, Morphic Medical, United States) was implanted for 1 year, showed data.

Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.

Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.

“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.

Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
 

Convenient, Reversible Procedure

Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.

Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.

The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.

“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.

Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
 

Over Half Maintained Full Improvement 2 Years Post Removal

A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m², and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.

Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.

Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m², A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.

Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).

Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.

Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.

Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.

Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”

Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.

EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m².
 

A version of this article appeared on Medscape.com.

LONDON — Weight loss, glycemic control, fatty liver, and the need for insulin all showed improvement in patients with both refractory type 2 diabetes and obesity after a gut liner known as EndoBarrier (RESET, Morphic Medical, United States) was implanted for 1 year, showed data.

Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.

Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.

“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.

Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
 

Convenient, Reversible Procedure

Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.

Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.

The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.

“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.

Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
 

Over Half Maintained Full Improvement 2 Years Post Removal

A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m², and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.

Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.

Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m², A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.

Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).

Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.

Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.

Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.

Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”

Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.

EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m².
 

A version of this article appeared on Medscape.com.

Lerodalcibep, a novel, third-generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, reduced low-density lipoprotein cholesterol (LDL-C) by more than 50% after 1 year in patients with or at a high risk for cardiovascular disease (CVD), new phase 3 results showed.

Newer, more stringent LDL targets in 90% of patients receiving lerodalcibep vs only 16% of those on placebo, despite concurrent treatment with a statin or statin plus ezetimibe.

“This hopefully gives doctors a more practical PCSK9 antagonist that’s small volume, can be administered monthly, and is an alternative to the every 2 week injection of monoclonal antibodies and probably more effective in LDL cholesterol–lowering compared to the small interfering RNA” medicines, study author Eric Klug, MBBCh, MMed, associate professor, Division of Cardiology, University of the Witwatersrand, Johannesburg, South Africa, told this news organization.

The findings from the LIBerate-HR trial were presented at the American College of Cardiology (ACC) Scientific Session 2024.
 

Additional Therapy Needed

The first goal is to get at least a 50% reduction in LDL-C, said Dr. Klug. The ACC, the American Heart Association, and the European Society of Cardiology recommended LDL-C of no more than 55 mg/dL as a goal for patients with CVD or who are at a very high risk for myocardial infarction or stroke and no more than 70 mg/dL for high-risk patients.

Most patients don’t get to that combined goal with statins and ezetimibe and need additional therapy, “and it appears the earlier you give the therapy the better,” said Dr. Klug.

Lerodalcibep is given as a low-dose (1.2-mL) monthly injection and is more convenient than other LDL-C–lowering options, said Dr. Klug. “This is a small-volume molecule that can be delivered subcutaneously once a month and can be kept on the shelf so it doesn’t need to be kept in the fridge, and you can travel with it.”

LIBerate-HR included 922 patients with CVD or at a high or very high risk for myocardial infarction or stroke at 66 centers in 11 countries. Over half (52%) fell into the at-risk category.

The mean age of participants was 64.5 years, 77% were White, and, notably, about 45% were women. Some 84% were taking a statin, 16.6% ezetimibe, a quarter had diabetes, and 10% had the more severe inherited familial hypercholesterolemia (FH).

Patients were randomly assigned to receive monthly 300-mg (1.2-mL) subcutaneous injections of lerodalcibep (n = 615) or placebo (n = 307) for 52 weeks.

The mean LDL-C at baseline was 116.9 mg/dL in the placebo group and 116.3 mg/dL in the treatment group.

The co-primary efficacy endpoints were the percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52 (average of the peak and trough dose).

Compared with placebo, lerodalcibep reduced LDL-C by 56.19% at week 52 (P < .0001) and by 62.69% at mean week 50/52 (P < .0001). The absolute decreases were 60.6 mg/dL at week 52 and 74.5 mg/dL for mean week 50/52.
 

Rule of Thumb

“There’s a sort of rule of thumb that for every 40 mg/dL that LDL-C is reduced, you reduce major adverse cardiovascular events (MACE) by 20%-23%,” said Dr. Klug. “So, by reducing LDL-C by 60 mg/dL at week 52, you’re reducing your risk of MACE maybe by 30% or 35%.”

All subgroups reaped the same benefit from the intervention, noted Dr. Klug. “Whether you were male or female, under age 65, over age 65, baseline BMI less than median or more than median, White, Black or other, baseline statin intensity, diabetic or not diabetic, diagnosis of FH or not, it made no difference.”

As for secondary outcomes, most patients attained the newer, more stringent guideline-recommended LDL targets. About 94% of all patients achieved a 50% or greater reduction in LDL-C compared to 19% on placebo. These percentages were 90% vs 12% for those at a high risk for CVD and 96% vs 21% for those with CVD or very high risk for CVD.

The treatment also reduced non–high-density lipoprotein cholesterol by 47%, apolipoprotein B by 43%, and Lp(a) by 33%.

Lerodalcibep was well-tolerated, with the number of patients with at least one adverse event similar to placebo (71.6% vs 68.1%) as was the case for the number with at least one serious adverse event (12.4% vs 13.4%).

Injection site reactions were mild to moderate. There was no difference in discontinuation rates due to these reactions (4.2% for the treatment and 4.6% for placebo).

A larger and longer trial to begin later this year should determine if the amount of LDL-C–lowering seen with lerodalcibep translates to greater reductions in cardiovascular events.

The company plans to file an application for approval to the US Food and Drug Administration in the next 2-4 months, said Dr. Klug.
 

Still Work to Do

During a press briefing, Dave L, Dixon, PharmD, professor and chair, Virginia Commonwealth University School of Pharmacy, Richmond, and member of the ACC Prevention of Cardiovascular Disease Council, congratulated the investigators “on moving this product forward and demonstrating the LDL-lowering efficacy, as well as providing some additional safety and tolerability data.”

He added it’s “clear” from the baseline LDL characteristics that “we have a lot of work to do in terms of helping patients achieve their lipid goals.”

Dr. Dixon noted up to about 30% of patients have some form of statin intolerance. “So, we really have to utilize our non-statin therapies, and unfortunately, we’re not doing a great job of that.”

That the trial enrolled so many women is “fantastic,” said Dr. Dixon, adding the investigators also “did a great job” of enrolling underrepresented minorities.

Having a once-a-month self-injection option “is great” and “fills a nice niche” for patients, said Dr. Dixon.

The study was funded by LIB Therapeutics, which manufactures lerodalcibep. Dr. Klug had no conflicts relevant to this study (he received honoraria from Novartis, Amgen, and Sanofi-Aventis).

A version of this article appeared on Medscape.com.

Lerodalcibep, a novel, third-generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, reduced low-density lipoprotein cholesterol (LDL-C) by more than 50% after 1 year in patients with or at a high risk for cardiovascular disease (CVD), new phase 3 results showed.

Newer, more stringent LDL targets in 90% of patients receiving lerodalcibep vs only 16% of those on placebo, despite concurrent treatment with a statin or statin plus ezetimibe.

“This hopefully gives doctors a more practical PCSK9 antagonist that’s small volume, can be administered monthly, and is an alternative to the every 2 week injection of monoclonal antibodies and probably more effective in LDL cholesterol–lowering compared to the small interfering RNA” medicines, study author Eric Klug, MBBCh, MMed, associate professor, Division of Cardiology, University of the Witwatersrand, Johannesburg, South Africa, told this news organization.

The findings from the LIBerate-HR trial were presented at the American College of Cardiology (ACC) Scientific Session 2024.
 

Additional Therapy Needed

The first goal is to get at least a 50% reduction in LDL-C, said Dr. Klug. The ACC, the American Heart Association, and the European Society of Cardiology recommended LDL-C of no more than 55 mg/dL as a goal for patients with CVD or who are at a very high risk for myocardial infarction or stroke and no more than 70 mg/dL for high-risk patients.

Most patients don’t get to that combined goal with statins and ezetimibe and need additional therapy, “and it appears the earlier you give the therapy the better,” said Dr. Klug.

Lerodalcibep is given as a low-dose (1.2-mL) monthly injection and is more convenient than other LDL-C–lowering options, said Dr. Klug. “This is a small-volume molecule that can be delivered subcutaneously once a month and can be kept on the shelf so it doesn’t need to be kept in the fridge, and you can travel with it.”

LIBerate-HR included 922 patients with CVD or at a high or very high risk for myocardial infarction or stroke at 66 centers in 11 countries. Over half (52%) fell into the at-risk category.

The mean age of participants was 64.5 years, 77% were White, and, notably, about 45% were women. Some 84% were taking a statin, 16.6% ezetimibe, a quarter had diabetes, and 10% had the more severe inherited familial hypercholesterolemia (FH).

Patients were randomly assigned to receive monthly 300-mg (1.2-mL) subcutaneous injections of lerodalcibep (n = 615) or placebo (n = 307) for 52 weeks.

The mean LDL-C at baseline was 116.9 mg/dL in the placebo group and 116.3 mg/dL in the treatment group.

The co-primary efficacy endpoints were the percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52 (average of the peak and trough dose).

Compared with placebo, lerodalcibep reduced LDL-C by 56.19% at week 52 (P < .0001) and by 62.69% at mean week 50/52 (P < .0001). The absolute decreases were 60.6 mg/dL at week 52 and 74.5 mg/dL for mean week 50/52.
 

Rule of Thumb

“There’s a sort of rule of thumb that for every 40 mg/dL that LDL-C is reduced, you reduce major adverse cardiovascular events (MACE) by 20%-23%,” said Dr. Klug. “So, by reducing LDL-C by 60 mg/dL at week 52, you’re reducing your risk of MACE maybe by 30% or 35%.”

All subgroups reaped the same benefit from the intervention, noted Dr. Klug. “Whether you were male or female, under age 65, over age 65, baseline BMI less than median or more than median, White, Black or other, baseline statin intensity, diabetic or not diabetic, diagnosis of FH or not, it made no difference.”

As for secondary outcomes, most patients attained the newer, more stringent guideline-recommended LDL targets. About 94% of all patients achieved a 50% or greater reduction in LDL-C compared to 19% on placebo. These percentages were 90% vs 12% for those at a high risk for CVD and 96% vs 21% for those with CVD or very high risk for CVD.

The treatment also reduced non–high-density lipoprotein cholesterol by 47%, apolipoprotein B by 43%, and Lp(a) by 33%.

Lerodalcibep was well-tolerated, with the number of patients with at least one adverse event similar to placebo (71.6% vs 68.1%) as was the case for the number with at least one serious adverse event (12.4% vs 13.4%).

Injection site reactions were mild to moderate. There was no difference in discontinuation rates due to these reactions (4.2% for the treatment and 4.6% for placebo).

A larger and longer trial to begin later this year should determine if the amount of LDL-C–lowering seen with lerodalcibep translates to greater reductions in cardiovascular events.

The company plans to file an application for approval to the US Food and Drug Administration in the next 2-4 months, said Dr. Klug.
 

Still Work to Do

During a press briefing, Dave L, Dixon, PharmD, professor and chair, Virginia Commonwealth University School of Pharmacy, Richmond, and member of the ACC Prevention of Cardiovascular Disease Council, congratulated the investigators “on moving this product forward and demonstrating the LDL-lowering efficacy, as well as providing some additional safety and tolerability data.”

He added it’s “clear” from the baseline LDL characteristics that “we have a lot of work to do in terms of helping patients achieve their lipid goals.”

Dr. Dixon noted up to about 30% of patients have some form of statin intolerance. “So, we really have to utilize our non-statin therapies, and unfortunately, we’re not doing a great job of that.”

That the trial enrolled so many women is “fantastic,” said Dr. Dixon, adding the investigators also “did a great job” of enrolling underrepresented minorities.

Having a once-a-month self-injection option “is great” and “fills a nice niche” for patients, said Dr. Dixon.

The study was funded by LIB Therapeutics, which manufactures lerodalcibep. Dr. Klug had no conflicts relevant to this study (he received honoraria from Novartis, Amgen, and Sanofi-Aventis).

A version of this article appeared on Medscape.com.

Lerodalcibep, a novel, third-generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, reduced low-density lipoprotein cholesterol (LDL-C) by more than 50% after 1 year in patients with or at a high risk for cardiovascular disease (CVD), new phase 3 results showed.

Newer, more stringent LDL targets in 90% of patients receiving lerodalcibep vs only 16% of those on placebo, despite concurrent treatment with a statin or statin plus ezetimibe.

“This hopefully gives doctors a more practical PCSK9 antagonist that’s small volume, can be administered monthly, and is an alternative to the every 2 week injection of monoclonal antibodies and probably more effective in LDL cholesterol–lowering compared to the small interfering RNA” medicines, study author Eric Klug, MBBCh, MMed, associate professor, Division of Cardiology, University of the Witwatersrand, Johannesburg, South Africa, told this news organization.

The findings from the LIBerate-HR trial were presented at the American College of Cardiology (ACC) Scientific Session 2024.
 

Additional Therapy Needed

The first goal is to get at least a 50% reduction in LDL-C, said Dr. Klug. The ACC, the American Heart Association, and the European Society of Cardiology recommended LDL-C of no more than 55 mg/dL as a goal for patients with CVD or who are at a very high risk for myocardial infarction or stroke and no more than 70 mg/dL for high-risk patients.

Most patients don’t get to that combined goal with statins and ezetimibe and need additional therapy, “and it appears the earlier you give the therapy the better,” said Dr. Klug.

Lerodalcibep is given as a low-dose (1.2-mL) monthly injection and is more convenient than other LDL-C–lowering options, said Dr. Klug. “This is a small-volume molecule that can be delivered subcutaneously once a month and can be kept on the shelf so it doesn’t need to be kept in the fridge, and you can travel with it.”

LIBerate-HR included 922 patients with CVD or at a high or very high risk for myocardial infarction or stroke at 66 centers in 11 countries. Over half (52%) fell into the at-risk category.

The mean age of participants was 64.5 years, 77% were White, and, notably, about 45% were women. Some 84% were taking a statin, 16.6% ezetimibe, a quarter had diabetes, and 10% had the more severe inherited familial hypercholesterolemia (FH).

Patients were randomly assigned to receive monthly 300-mg (1.2-mL) subcutaneous injections of lerodalcibep (n = 615) or placebo (n = 307) for 52 weeks.

The mean LDL-C at baseline was 116.9 mg/dL in the placebo group and 116.3 mg/dL in the treatment group.

The co-primary efficacy endpoints were the percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52 (average of the peak and trough dose).

Compared with placebo, lerodalcibep reduced LDL-C by 56.19% at week 52 (P < .0001) and by 62.69% at mean week 50/52 (P < .0001). The absolute decreases were 60.6 mg/dL at week 52 and 74.5 mg/dL for mean week 50/52.
 

Rule of Thumb

“There’s a sort of rule of thumb that for every 40 mg/dL that LDL-C is reduced, you reduce major adverse cardiovascular events (MACE) by 20%-23%,” said Dr. Klug. “So, by reducing LDL-C by 60 mg/dL at week 52, you’re reducing your risk of MACE maybe by 30% or 35%.”

All subgroups reaped the same benefit from the intervention, noted Dr. Klug. “Whether you were male or female, under age 65, over age 65, baseline BMI less than median or more than median, White, Black or other, baseline statin intensity, diabetic or not diabetic, diagnosis of FH or not, it made no difference.”

As for secondary outcomes, most patients attained the newer, more stringent guideline-recommended LDL targets. About 94% of all patients achieved a 50% or greater reduction in LDL-C compared to 19% on placebo. These percentages were 90% vs 12% for those at a high risk for CVD and 96% vs 21% for those with CVD or very high risk for CVD.

The treatment also reduced non–high-density lipoprotein cholesterol by 47%, apolipoprotein B by 43%, and Lp(a) by 33%.

Lerodalcibep was well-tolerated, with the number of patients with at least one adverse event similar to placebo (71.6% vs 68.1%) as was the case for the number with at least one serious adverse event (12.4% vs 13.4%).

Injection site reactions were mild to moderate. There was no difference in discontinuation rates due to these reactions (4.2% for the treatment and 4.6% for placebo).

A larger and longer trial to begin later this year should determine if the amount of LDL-C–lowering seen with lerodalcibep translates to greater reductions in cardiovascular events.

The company plans to file an application for approval to the US Food and Drug Administration in the next 2-4 months, said Dr. Klug.
 

Still Work to Do

During a press briefing, Dave L, Dixon, PharmD, professor and chair, Virginia Commonwealth University School of Pharmacy, Richmond, and member of the ACC Prevention of Cardiovascular Disease Council, congratulated the investigators “on moving this product forward and demonstrating the LDL-lowering efficacy, as well as providing some additional safety and tolerability data.”

He added it’s “clear” from the baseline LDL characteristics that “we have a lot of work to do in terms of helping patients achieve their lipid goals.”

Dr. Dixon noted up to about 30% of patients have some form of statin intolerance. “So, we really have to utilize our non-statin therapies, and unfortunately, we’re not doing a great job of that.”

That the trial enrolled so many women is “fantastic,” said Dr. Dixon, adding the investigators also “did a great job” of enrolling underrepresented minorities.

Having a once-a-month self-injection option “is great” and “fills a nice niche” for patients, said Dr. Dixon.

The study was funded by LIB Therapeutics, which manufactures lerodalcibep. Dr. Klug had no conflicts relevant to this study (he received honoraria from Novartis, Amgen, and Sanofi-Aventis).

A version of this article appeared on Medscape.com.

PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.

The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?

Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.

While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
 

Microbiota in IBS 

Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota. 

Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use. 

This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.

Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.

In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.

Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.

Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
 

Recent Guideline 

In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.

Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
 

Efficacy and Availability 

Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.

Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.

“Probiotic efficacy largely depends on the bacterial species, strain, and clinical situation treated. Only probiotics with demonstrated clinical efficacy in randomized placebo-controlled trials should be recommended,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
 

Effective Probiotics 

B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.

L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.

The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.

B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.

“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”

Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
 

Mechanisms of Action 

In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.

Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).

B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.

B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.

Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).

Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.

Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.

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

PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.

The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?

Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.

While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
 

Microbiota in IBS 

Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota. 

Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use. 

This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.

Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.

In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.

Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.

Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
 

Recent Guideline 

In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.

Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
 

Efficacy and Availability 

Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.

Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.

“Probiotic efficacy largely depends on the bacterial species, strain, and clinical situation treated. Only probiotics with demonstrated clinical efficacy in randomized placebo-controlled trials should be recommended,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
 

Effective Probiotics 

B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.

L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.

The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.

B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.

“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”

Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
 

Mechanisms of Action 

In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.

Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).

B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.

B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.

Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).

Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.

Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.

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

PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.

The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?

Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.

While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
 

Microbiota in IBS 

Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota. 

Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use. 

This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.

Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.

In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.

Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.

Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
 

Recent Guideline 

In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.

Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
 

Efficacy and Availability 

Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.

Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.

“Probiotic efficacy largely depends on the bacterial species, strain, and clinical situation treated. Only probiotics with demonstrated clinical efficacy in randomized placebo-controlled trials should be recommended,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
 

Effective Probiotics 

B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.

L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.

The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.

B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.

“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”

Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
 

Mechanisms of Action 

In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.

Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).

B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.

B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.

Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).

Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.

Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.

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

TOPLINE:

The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.

METHODOLOGY:

• MDA5 antibody-positive DM is a rare DM subtype associated with ILD, which is categorized into rapidly progressive ILD (RPILD) and chronic ILD, with the former having a particularly high mortality rate.
• In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
• The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.

TAKEAWAY:

• Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
• ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
• The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
• Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.

IN PRACTICE:

“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.

SOURCE:

This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.

LIMITATIONS:

Study limitations were the study’s retrospective design and small sample size.

DISCLOSURES:

No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.

METHODOLOGY:

• MDA5 antibody-positive DM is a rare DM subtype associated with ILD, which is categorized into rapidly progressive ILD (RPILD) and chronic ILD, with the former having a particularly high mortality rate.
• In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
• The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.

TAKEAWAY:

• Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
• ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
• The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
• Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.

IN PRACTICE:

“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.

SOURCE:

This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.

LIMITATIONS:

Study limitations were the study’s retrospective design and small sample size.

DISCLOSURES:

No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.

METHODOLOGY:

• MDA5 antibody-positive DM is a rare DM subtype associated with ILD, which is categorized into rapidly progressive ILD (RPILD) and chronic ILD, with the former having a particularly high mortality rate.
• In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
• The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.

TAKEAWAY:

• Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
• ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
• The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
• Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.

IN PRACTICE:

“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.

SOURCE:

This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.

LIMITATIONS:

Study limitations were the study’s retrospective design and small sample size.

DISCLOSURES:

No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.

A version of this article appeared on Medscape.com.

BY DEEPA VARMA

TOPLINE:

In patients with polycystic ovary syndrome (PCOS), laser and light therapies, alone or in combination with pharmacological agents, improve hirsutism and psychological well-being in women, according to the results of a systematic review.

METHODOLOGY:

• Hirsutism, which affects 70%-80% of women with PCOS, is frequently marginalized as a cosmetic issue by healthcare providers, despite its significant psychological repercussions, including diminished self-esteem, reduced quality of life, and heightened depression.
• The 2023 international evidence-based PCOS guideline considers managing hirsutism a priority in women with PCOS.
• Researchers reviewed six studies (four randomized controlled trials and two cohort studies), which included 423 patients with PCOS who underwent laser or light-based hair reduction therapies, published through 2022.
• The studies evaluated the alexandrite laser, diode laser, and intense pulsed light (IPL) therapy, with and without pharmacological treatments. The main outcomes were hirsutism severity, psychological outcome, and adverse events.

TAKEAWAY:

• Alexandrite laser (wavelength, 755 nm) showed effective hair reduction and improved patient satisfaction (one study); high-fluence treatment yielded better outcomes than low-fluence treatment (one study). Alexandrite laser 755 nm also showed longer hair-free intervals and greater hair reduction than IPL therapy at 650-1000 nm (one study).
• Combined IPL (600 nm) and metformin therapy improved hirsutism and hair count reduction compared with IPL alone, but with more side effects (one study).
• Diode laser treatments (810 nm) with combined oral contraceptives improved hirsutism and related quality of life measures compared with diode laser alone or with metformin (one study).
• Comparing two diode lasers (wavelengths, 810 nm), low-fluence, high repetition laser showed superior hair width reduction and lower pain scores than high fluence, low-repetition laser (one study).

IN PRACTICE:

Laser and light treatments alone or combined with other treatments have demonstrated “encouraging results in reducing hirsutism severity, enhancing psychological well-being, and improving overall quality of life for affected individuals,” the authors wrote, noting that additional high-quality trials evaluating these treatments, which include more patients with different skin tones, are needed.

SOURCE:

The first author of the review is Katrina Tan, MD, Monash Health, Department of Dermatology, Melbourne, Victoria, Australia, and it was published online in JAMA Dermatology.

LIMITATIONS:

Limitations include low certainty of evidence because of the observational nature of some of the studies, the small number of studies, and underrepresentation of darker skin types, limiting generalizability.

DISCLOSURES:

The review is part of an update to the PCOS guideline, which was funded by the Australian National Health and Medical Research Council through various organizations. Several authors reported receiving grants and personal fees outside this work. Dr. Tan was a member of the 2023 PCOS guideline evidence team. Other authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

BY DEEPA VARMA

TOPLINE:

In patients with polycystic ovary syndrome (PCOS), laser and light therapies, alone or in combination with pharmacological agents, improve hirsutism and psychological well-being in women, according to the results of a systematic review.

METHODOLOGY:

• Hirsutism, which affects 70%-80% of women with PCOS, is frequently marginalized as a cosmetic issue by healthcare providers, despite its significant psychological repercussions, including diminished self-esteem, reduced quality of life, and heightened depression.
• The 2023 international evidence-based PCOS guideline considers managing hirsutism a priority in women with PCOS.
• Researchers reviewed six studies (four randomized controlled trials and two cohort studies), which included 423 patients with PCOS who underwent laser or light-based hair reduction therapies, published through 2022.
• The studies evaluated the alexandrite laser, diode laser, and intense pulsed light (IPL) therapy, with and without pharmacological treatments. The main outcomes were hirsutism severity, psychological outcome, and adverse events.

TAKEAWAY:

• Alexandrite laser (wavelength, 755 nm) showed effective hair reduction and improved patient satisfaction (one study); high-fluence treatment yielded better outcomes than low-fluence treatment (one study). Alexandrite laser 755 nm also showed longer hair-free intervals and greater hair reduction than IPL therapy at 650-1000 nm (one study).
• Combined IPL (600 nm) and metformin therapy improved hirsutism and hair count reduction compared with IPL alone, but with more side effects (one study).
• Diode laser treatments (810 nm) with combined oral contraceptives improved hirsutism and related quality of life measures compared with diode laser alone or with metformin (one study).
• Comparing two diode lasers (wavelengths, 810 nm), low-fluence, high repetition laser showed superior hair width reduction and lower pain scores than high fluence, low-repetition laser (one study).

IN PRACTICE:

Laser and light treatments alone or combined with other treatments have demonstrated “encouraging results in reducing hirsutism severity, enhancing psychological well-being, and improving overall quality of life for affected individuals,” the authors wrote, noting that additional high-quality trials evaluating these treatments, which include more patients with different skin tones, are needed.

SOURCE:

The first author of the review is Katrina Tan, MD, Monash Health, Department of Dermatology, Melbourne, Victoria, Australia, and it was published online in JAMA Dermatology.

LIMITATIONS:

Limitations include low certainty of evidence because of the observational nature of some of the studies, the small number of studies, and underrepresentation of darker skin types, limiting generalizability.

DISCLOSURES:

The review is part of an update to the PCOS guideline, which was funded by the Australian National Health and Medical Research Council through various organizations. Several authors reported receiving grants and personal fees outside this work. Dr. Tan was a member of the 2023 PCOS guideline evidence team. Other authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

BY DEEPA VARMA

TOPLINE:

In patients with polycystic ovary syndrome (PCOS), laser and light therapies, alone or in combination with pharmacological agents, improve hirsutism and psychological well-being in women, according to the results of a systematic review.

METHODOLOGY:

• Hirsutism, which affects 70%-80% of women with PCOS, is frequently marginalized as a cosmetic issue by healthcare providers, despite its significant psychological repercussions, including diminished self-esteem, reduced quality of life, and heightened depression.
• The 2023 international evidence-based PCOS guideline considers managing hirsutism a priority in women with PCOS.
• Researchers reviewed six studies (four randomized controlled trials and two cohort studies), which included 423 patients with PCOS who underwent laser or light-based hair reduction therapies, published through 2022.
• The studies evaluated the alexandrite laser, diode laser, and intense pulsed light (IPL) therapy, with and without pharmacological treatments. The main outcomes were hirsutism severity, psychological outcome, and adverse events.

TAKEAWAY:

• Alexandrite laser (wavelength, 755 nm) showed effective hair reduction and improved patient satisfaction (one study); high-fluence treatment yielded better outcomes than low-fluence treatment (one study). Alexandrite laser 755 nm also showed longer hair-free intervals and greater hair reduction than IPL therapy at 650-1000 nm (one study).
• Combined IPL (600 nm) and metformin therapy improved hirsutism and hair count reduction compared with IPL alone, but with more side effects (one study).
• Diode laser treatments (810 nm) with combined oral contraceptives improved hirsutism and related quality of life measures compared with diode laser alone or with metformin (one study).
• Comparing two diode lasers (wavelengths, 810 nm), low-fluence, high repetition laser showed superior hair width reduction and lower pain scores than high fluence, low-repetition laser (one study).

IN PRACTICE:

Laser and light treatments alone or combined with other treatments have demonstrated “encouraging results in reducing hirsutism severity, enhancing psychological well-being, and improving overall quality of life for affected individuals,” the authors wrote, noting that additional high-quality trials evaluating these treatments, which include more patients with different skin tones, are needed.

SOURCE:

The first author of the review is Katrina Tan, MD, Monash Health, Department of Dermatology, Melbourne, Victoria, Australia, and it was published online in JAMA Dermatology.

LIMITATIONS:

Limitations include low certainty of evidence because of the observational nature of some of the studies, the small number of studies, and underrepresentation of darker skin types, limiting generalizability.

DISCLOSURES:

The review is part of an update to the PCOS guideline, which was funded by the Australian National Health and Medical Research Council through various organizations. Several authors reported receiving grants and personal fees outside this work. Dr. Tan was a member of the 2023 PCOS guideline evidence team. Other authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Results from a preliminary clinical trial demonstrated the obesity drug, tirzepatide, effectively treated obstructive sleep apnea (OSA), according to information sent to investors of the pharmaceutical company, Eli Lilly.

Indiana-based Eli Lilly sells tirzepatide under the brand name Zepbound, which was approved by the FDA in November to treat overweight and obesity. Tirzepatide is also marketed under the name Mounjaro to treat diabetes, and it’s among the same class of drugs as other well-known weight loss and diabetes drugs like Ozempic and Wegovy.

The newly announced results came from a pair of studies that followed people with moderate to severe OSA who also had obesity. People in the study took tirzepatide, which is given by injection, for one year. One study evaluated people who were using CPAP during sleep, and another study included people who didn’t use the device. People in both studies taking tirzepatide had significant reductions in sleep events and also lost about 20% of body weight. About 70% of people in the studies were men.

The findings have not yet been published in a peer-reviewed medical journal, and the preliminary results were announced by Eli Lilly because of reporting requirements related to information that could affect stock prices. The company indicated that detailed results will be presented at a conference of the American Diabetes Association in June and will be submitted to a peer-reviewed journal for consideration of publication. The company also plans to submit the information to the FDA for approval consideration mid-year, the investor news release stated.

People in the study taking tirzepatide on average experienced 63% fewer instances of reduced oxygen due to breathing changes, or events when breathing entirely stopped, Eli Lilly reported.

A sleep expert from Washington University in St. Louis told The New York Times the initial findings were extremely positive and noted that tirzepatide works to treat the underlying cause of sleep apnea, rather than current treatments that just address symptoms.

Tirzepatide “is a great alternative for people who are obese and can’t use CPAP or are on CPAP and want to improve the effect,” Eric Landsness, MD, PhD, told The New York Times. 

Eli Lilly indicated the most commonly reported adverse events in the studies were diarrhea, nausea, vomiting, and constipation.

An estimated 39 million people have OSA and about 33 million people use CPAP machines, according to The National Council on Aging. The condition has been increasingly diagnosed in recent years and becomes more likely to affect people as they get older.

A version of this article appeared on WebMD.com.

Results from a preliminary clinical trial demonstrated the obesity drug, tirzepatide, effectively treated obstructive sleep apnea (OSA), according to information sent to investors of the pharmaceutical company, Eli Lilly.

Indiana-based Eli Lilly sells tirzepatide under the brand name Zepbound, which was approved by the FDA in November to treat overweight and obesity. Tirzepatide is also marketed under the name Mounjaro to treat diabetes, and it’s among the same class of drugs as other well-known weight loss and diabetes drugs like Ozempic and Wegovy.

The newly announced results came from a pair of studies that followed people with moderate to severe OSA who also had obesity. People in the study took tirzepatide, which is given by injection, for one year. One study evaluated people who were using CPAP during sleep, and another study included people who didn’t use the device. People in both studies taking tirzepatide had significant reductions in sleep events and also lost about 20% of body weight. About 70% of people in the studies were men.

The findings have not yet been published in a peer-reviewed medical journal, and the preliminary results were announced by Eli Lilly because of reporting requirements related to information that could affect stock prices. The company indicated that detailed results will be presented at a conference of the American Diabetes Association in June and will be submitted to a peer-reviewed journal for consideration of publication. The company also plans to submit the information to the FDA for approval consideration mid-year, the investor news release stated.

People in the study taking tirzepatide on average experienced 63% fewer instances of reduced oxygen due to breathing changes, or events when breathing entirely stopped, Eli Lilly reported.

A sleep expert from Washington University in St. Louis told The New York Times the initial findings were extremely positive and noted that tirzepatide works to treat the underlying cause of sleep apnea, rather than current treatments that just address symptoms.

Tirzepatide “is a great alternative for people who are obese and can’t use CPAP or are on CPAP and want to improve the effect,” Eric Landsness, MD, PhD, told The New York Times. 

Eli Lilly indicated the most commonly reported adverse events in the studies were diarrhea, nausea, vomiting, and constipation.

An estimated 39 million people have OSA and about 33 million people use CPAP machines, according to The National Council on Aging. The condition has been increasingly diagnosed in recent years and becomes more likely to affect people as they get older.

A version of this article appeared on WebMD.com.

Results from a preliminary clinical trial demonstrated the obesity drug, tirzepatide, effectively treated obstructive sleep apnea (OSA), according to information sent to investors of the pharmaceutical company, Eli Lilly.

Indiana-based Eli Lilly sells tirzepatide under the brand name Zepbound, which was approved by the FDA in November to treat overweight and obesity. Tirzepatide is also marketed under the name Mounjaro to treat diabetes, and it’s among the same class of drugs as other well-known weight loss and diabetes drugs like Ozempic and Wegovy.

The newly announced results came from a pair of studies that followed people with moderate to severe OSA who also had obesity. People in the study took tirzepatide, which is given by injection, for one year. One study evaluated people who were using CPAP during sleep, and another study included people who didn’t use the device. People in both studies taking tirzepatide had significant reductions in sleep events and also lost about 20% of body weight. About 70% of people in the studies were men.

The findings have not yet been published in a peer-reviewed medical journal, and the preliminary results were announced by Eli Lilly because of reporting requirements related to information that could affect stock prices. The company indicated that detailed results will be presented at a conference of the American Diabetes Association in June and will be submitted to a peer-reviewed journal for consideration of publication. The company also plans to submit the information to the FDA for approval consideration mid-year, the investor news release stated.

People in the study taking tirzepatide on average experienced 63% fewer instances of reduced oxygen due to breathing changes, or events when breathing entirely stopped, Eli Lilly reported.

A sleep expert from Washington University in St. Louis told The New York Times the initial findings were extremely positive and noted that tirzepatide works to treat the underlying cause of sleep apnea, rather than current treatments that just address symptoms.

Tirzepatide “is a great alternative for people who are obese and can’t use CPAP or are on CPAP and want to improve the effect,” Eric Landsness, MD, PhD, told The New York Times. 

Eli Lilly indicated the most commonly reported adverse events in the studies were diarrhea, nausea, vomiting, and constipation.

An estimated 39 million people have OSA and about 33 million people use CPAP machines, according to The National Council on Aging. The condition has been increasingly diagnosed in recent years and becomes more likely to affect people as they get older.

A version of this article appeared on WebMD.com.

A mix of microbes may help explain why some people develop dry eye disease, new research showed.

This finding suggests that bacteria may cause dry eye and could someday point to new treatments for the condition and related disorders, which affect an estimated 27 million Americans, according to researchers.

Current treatments aim to preserve and enhance tears and tear production to ease the grittiness and itchiness that accompany dry eye disease. 

To examine the role of the ocular microbiome in dry eye disease, scientists in Texas analyzed swab samples from 30 men and women, nine of whom had dry eye.

They found Streptococcus and Pedobacter species were the most common bacteria in healthy eyes.

In people with dry eye, however, more Acinetobacter species were detected.

“We think the metabolites produced by these bacteria are responsible for dry eye conditions,” study coauthor Pallavi Sharma said in a news release about the findings. 

Sharma, a graduate student at Stephen F. Austin State University in Nacogdoches, Texas, presented this research last month at the annual meeting of the American Society for Biochemistry and Molecular Biology. The research team was led by Alexandra Van Kley, PhD, a professor of biology at the university.

“Once we understand the eye microbiota properly, it will improve disease diagnosis at an early stage,” Van Kley predicted in the news release. “This knowledge can also serve as a catalyst for developing innovative therapies aimed at preventing and treating ocular disease as well as those that affect the central microbiome site: The gut.”

Investigators in Australia have conducted similar experiments in patients with meibomian gland dysfunction, a condition marked by underproduction of key oils in the eye.

One group reported in August 2023 the finding of “detectable differences in the bacterial richness, diversity, and community structure of the conjunctiva and eyelid margin between individuals with meibomian gland dysfunction with and without lacrimal dysfunction, as well as to healthy controls.”

More research is needed to confirm and understand the findings, though, and “to determine if manipulating the microbiome could be a potential treatment for the condition,” they wrote.

A version of this article appeared on Medscape.com.

A mix of microbes may help explain why some people develop dry eye disease, new research showed.

This finding suggests that bacteria may cause dry eye and could someday point to new treatments for the condition and related disorders, which affect an estimated 27 million Americans, according to researchers.

Current treatments aim to preserve and enhance tears and tear production to ease the grittiness and itchiness that accompany dry eye disease. 

To examine the role of the ocular microbiome in dry eye disease, scientists in Texas analyzed swab samples from 30 men and women, nine of whom had dry eye.

They found Streptococcus and Pedobacter species were the most common bacteria in healthy eyes.

In people with dry eye, however, more Acinetobacter species were detected.

“We think the metabolites produced by these bacteria are responsible for dry eye conditions,” study coauthor Pallavi Sharma said in a news release about the findings. 

Sharma, a graduate student at Stephen F. Austin State University in Nacogdoches, Texas, presented this research last month at the annual meeting of the American Society for Biochemistry and Molecular Biology. The research team was led by Alexandra Van Kley, PhD, a professor of biology at the university.

“Once we understand the eye microbiota properly, it will improve disease diagnosis at an early stage,” Van Kley predicted in the news release. “This knowledge can also serve as a catalyst for developing innovative therapies aimed at preventing and treating ocular disease as well as those that affect the central microbiome site: The gut.”

Investigators in Australia have conducted similar experiments in patients with meibomian gland dysfunction, a condition marked by underproduction of key oils in the eye.

One group reported in August 2023 the finding of “detectable differences in the bacterial richness, diversity, and community structure of the conjunctiva and eyelid margin between individuals with meibomian gland dysfunction with and without lacrimal dysfunction, as well as to healthy controls.”

More research is needed to confirm and understand the findings, though, and “to determine if manipulating the microbiome could be a potential treatment for the condition,” they wrote.

A version of this article appeared on Medscape.com.

A mix of microbes may help explain why some people develop dry eye disease, new research showed.

This finding suggests that bacteria may cause dry eye and could someday point to new treatments for the condition and related disorders, which affect an estimated 27 million Americans, according to researchers.

Current treatments aim to preserve and enhance tears and tear production to ease the grittiness and itchiness that accompany dry eye disease. 

To examine the role of the ocular microbiome in dry eye disease, scientists in Texas analyzed swab samples from 30 men and women, nine of whom had dry eye.

They found Streptococcus and Pedobacter species were the most common bacteria in healthy eyes.

In people with dry eye, however, more Acinetobacter species were detected.

“We think the metabolites produced by these bacteria are responsible for dry eye conditions,” study coauthor Pallavi Sharma said in a news release about the findings. 

Sharma, a graduate student at Stephen F. Austin State University in Nacogdoches, Texas, presented this research last month at the annual meeting of the American Society for Biochemistry and Molecular Biology. The research team was led by Alexandra Van Kley, PhD, a professor of biology at the university.

“Once we understand the eye microbiota properly, it will improve disease diagnosis at an early stage,” Van Kley predicted in the news release. “This knowledge can also serve as a catalyst for developing innovative therapies aimed at preventing and treating ocular disease as well as those that affect the central microbiome site: The gut.”

Investigators in Australia have conducted similar experiments in patients with meibomian gland dysfunction, a condition marked by underproduction of key oils in the eye.

One group reported in August 2023 the finding of “detectable differences in the bacterial richness, diversity, and community structure of the conjunctiva and eyelid margin between individuals with meibomian gland dysfunction with and without lacrimal dysfunction, as well as to healthy controls.”

More research is needed to confirm and understand the findings, though, and “to determine if manipulating the microbiome could be a potential treatment for the condition,” they wrote.

A version of this article appeared on Medscape.com.

SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.

“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”

LucaLorenzelli/Thinkstock

Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:

Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.

As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”

Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”

He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.


 

Courtesy University of California, San Diego

Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”

Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.

Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”

Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”

Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.

SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.

“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”

LucaLorenzelli/Thinkstock

Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:

Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.

As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”

Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”

He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.


 

Courtesy University of California, San Diego

Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”

Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.

Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”

Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”

Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.

SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.

“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”

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Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:

Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.

As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”

Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”

He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.


 

Courtesy University of California, San Diego

Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”

Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.

Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”

Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”

Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.