Federal Practitioner

Insurance companies are starting to send warning letters to doctors and health care providers suspected of off-label prescribing for the drug Ozempic. 

The warning letters, first reported by The Washington Post, include threats such as the possibility of reporting “suspected inappropriate or fraudulent activity ... to the state licensure board, federal and/or state law enforcement.”

It’s the latest chapter in the story of the popular, highly effective, and very expensive drug intended for diabetes that results in quick weight loss. Off-label prescribing means a medicine has been prescribed for a reason other than the uses approved by the Food and Drug Administration.  The practice is common and legal (the U.S. Agency for Healthcare Research and Quality says one in five prescriptions in the U.S. are off label). 

But insurance companies are pushing back because many do not cover weight loss medications, while they do cover diabetes treatments. The insurance company letters suggest that prescribers are failing to document in a person’s medical record that the person actually has diabetes. 

Ozempic, which is FDA approved for treatment of diabetes, is similar to the drug Wegovy, which is approved to be used for weight loss. Ozempic typically costs more than $900 per month. Both Wegovy and Ozempic contain semaglutide, which mimics a hormone that helps the brain regulate appetite and food intake. Clinical studies show that after taking semaglutide for more than 5 years, people lose on average 17% of their body weight. But once they stop taking it, most people regain much of the weight. 

Demand for both Ozempic and Wegovy has been surging, leading to shortages and tactics to acquire the drugs outside of the United States, as well as warnings from public health officials about the dangers of knockoff versions of the drugs. The Centers for Disease Control and Prevention says 42% of people in the United States are obese.

“Obesity is a complex disease involving an excessive amount of body fat,” the Mayo Clinic explained. “Obesity isn’t just a cosmetic concern. It’s a medical problem that increases the risk of other diseases and health problems, such as heart disease, diabetes, high blood pressure, and certain cancers.”

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

Insurance companies are starting to send warning letters to doctors and health care providers suspected of off-label prescribing for the drug Ozempic. 

The warning letters, first reported by The Washington Post, include threats such as the possibility of reporting “suspected inappropriate or fraudulent activity ... to the state licensure board, federal and/or state law enforcement.”

It’s the latest chapter in the story of the popular, highly effective, and very expensive drug intended for diabetes that results in quick weight loss. Off-label prescribing means a medicine has been prescribed for a reason other than the uses approved by the Food and Drug Administration.  The practice is common and legal (the U.S. Agency for Healthcare Research and Quality says one in five prescriptions in the U.S. are off label). 

But insurance companies are pushing back because many do not cover weight loss medications, while they do cover diabetes treatments. The insurance company letters suggest that prescribers are failing to document in a person’s medical record that the person actually has diabetes. 

Ozempic, which is FDA approved for treatment of diabetes, is similar to the drug Wegovy, which is approved to be used for weight loss. Ozempic typically costs more than $900 per month. Both Wegovy and Ozempic contain semaglutide, which mimics a hormone that helps the brain regulate appetite and food intake. Clinical studies show that after taking semaglutide for more than 5 years, people lose on average 17% of their body weight. But once they stop taking it, most people regain much of the weight. 

Demand for both Ozempic and Wegovy has been surging, leading to shortages and tactics to acquire the drugs outside of the United States, as well as warnings from public health officials about the dangers of knockoff versions of the drugs. The Centers for Disease Control and Prevention says 42% of people in the United States are obese.

“Obesity is a complex disease involving an excessive amount of body fat,” the Mayo Clinic explained. “Obesity isn’t just a cosmetic concern. It’s a medical problem that increases the risk of other diseases and health problems, such as heart disease, diabetes, high blood pressure, and certain cancers.”

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

Insurance companies are starting to send warning letters to doctors and health care providers suspected of off-label prescribing for the drug Ozempic. 

The warning letters, first reported by The Washington Post, include threats such as the possibility of reporting “suspected inappropriate or fraudulent activity ... to the state licensure board, federal and/or state law enforcement.”

It’s the latest chapter in the story of the popular, highly effective, and very expensive drug intended for diabetes that results in quick weight loss. Off-label prescribing means a medicine has been prescribed for a reason other than the uses approved by the Food and Drug Administration.  The practice is common and legal (the U.S. Agency for Healthcare Research and Quality says one in five prescriptions in the U.S. are off label). 

But insurance companies are pushing back because many do not cover weight loss medications, while they do cover diabetes treatments. The insurance company letters suggest that prescribers are failing to document in a person’s medical record that the person actually has diabetes. 

Ozempic, which is FDA approved for treatment of diabetes, is similar to the drug Wegovy, which is approved to be used for weight loss. Ozempic typically costs more than $900 per month. Both Wegovy and Ozempic contain semaglutide, which mimics a hormone that helps the brain regulate appetite and food intake. Clinical studies show that after taking semaglutide for more than 5 years, people lose on average 17% of their body weight. But once they stop taking it, most people regain much of the weight. 

Demand for both Ozempic and Wegovy has been surging, leading to shortages and tactics to acquire the drugs outside of the United States, as well as warnings from public health officials about the dangers of knockoff versions of the drugs. The Centers for Disease Control and Prevention says 42% of people in the United States are obese.

“Obesity is a complex disease involving an excessive amount of body fat,” the Mayo Clinic explained. “Obesity isn’t just a cosmetic concern. It’s a medical problem that increases the risk of other diseases and health problems, such as heart disease, diabetes, high blood pressure, and certain cancers.”

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

Johnna Mendenall had never been “the skinny friend,” she said, but the demands of motherhood – along with a sedentary desk job – made weight management even more difficult. Worried that family type 2 diabetes would catch up with her, she decided to start Wegovy shots for weight loss.

She was nervous about potential side effects. It took 5 days of staring at the Wegovy pen before she worked up the nerve for her first .25-milligram shot. And sure enough, the side effects came on strong.

“The nausea kicked in,” she said. “When I increased my dose to 1 milligram, I spent the entire night from 10 p.m. to 5 a.m. vomiting. I almost quit that day.”

Ms. Mendenall is among a growing number of people sharing personal stories online about the weight loss medication Wegovy – and similar drugs – delving into their sometimes unpleasant, and potentially gut-wrenching, side effects. 

While gastrointestinal (GI) symptoms seem to be the most common, a laundry list of others has been discussed in the news, on TikTok, and across online forums. Those include “Ozempic face,” or the gaunt look some get after taking the medication, along with hair loss, anxiety, depression, and debilitating fatigue. 

Ms. Mendenall’s primary side effects have been vomiting, fatigue, and severe constipation, but she has also seen some positive changes: The “food noise,” or the urge to eat when she isn’t hungry, is gone. Since her first dose 12 weeks ago, she has gone from 236 pounds to 215. 
 

Warning label

Wegovy’s active ingredient, semaglutide, mimics the role of a natural hormone called glucagonlike peptide–1 (GLP-1), which helps you feel well fed. Semaglutide is used at a lower dose under the brand name Ozempic, which is approved for type 2 diabetes and used off-label for weight loss.  

Both Ozempic and Wegovy come with a warning label for potential side effects, the most common ones being nausea, diarrhea, stomach pain, and vomiting.

With the surging popularity of semaglutide, more people are getting prescriptions through telemedicine companies, forgoing more in-depth consultations, leading to more side effects, said Caroline Apovian, MD, professor of medicine at Harvard Medical School and codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, Boston.

Specialists say starting with low doses and gradually increasing over time helps avoid side effects, but insurance companies often require a faster timeline to continue covering the medication, Dr. Apovian said. 

“Insurance companies are practicing medicine for us by demanding the patient go up in dosage [too quickly],” she explained. 

Ms. Mendenall’s insurance has paid for her Wegovy shots, but without that coverage, she said it would cost her $1,200 per month. 

There are similar medications on the market, such as liraglutide, sold under the name Saxenda. But it is a daily, rather than a weekly, shot and also comes with side effects and has been shown to be less effective. In one clinical trial, the people being studied saw their average body weight over 68 weeks drop by 15.8% with semaglutide, and by 6.4% with liraglutide.

Tirzepatide, branded Mounjaro – a type 2 diabetes drug made by Eli Lilly that may soon gain Food and Drug Administration approval for weight loss – could have fewer side effects. In clinical trials, 44% of those taking semaglutide had nausea and 31% reported diarrhea, compared with 33% and 23% of those taking tirzepatide, although no trial has directly compared the two agents. 
 

Loss of bowel control 

For now, Wegovy and Saxenda are the only GLP-1 agonist shots authorized for weight loss, and their maker, Danish drug company Novo Nordisk, is facing its second shortage of Wegovy amid growing demand. 

Personal stories online about semaglutide range from overwhelmingly positive – just what some need to win a lifelong battle with obesity – to harsh scenarios with potentially long-term health consequences, and everything in between. 

One private community on Reddit is dedicated to a particularly unpleasant side effect: loss of bowel control while sleeping. Others have reported uncontrollable vomiting.

Kimberly Carew of Clearwater, Fla., started on .5 milligrams of Ozempic last year after her rheumatologist and endocrinologist suggested it to treat her type 2 diabetes. She was told it came with the bonus of weight loss, which she was hoping would help with her joint and back pain. 

But after she increased the dose to 1 milligram, her GI symptoms, which started out mild, became unbearable. She couldn’t keep food down, and when she vomited, the food would often come up whole, she said. 

“One night I ate ramen before bed. And the next morning, it came out just as it went down,” said Ms. Carew, 42, a registered mental health counseling intern. “I was getting severe heartburn and could not take a couple bites of food without getting nauseous.”

She also had “sulfur burps,” a side effect discussed by some Ozempic users, causing her to taste rotten egg sometimes.

She was diagnosed with gastroparesis. Some types of gastroparesis can be resolved by discontinuing GLP-1 medications, as referenced in two case reports in the Journal of Investigative Medicine. 
 

Gut hormone

GI symptoms are most common with semaglutide because the hormone it imitates, GLP-1, is secreted by cells in the stomach, small intestines, and pancreas, said Anne Peters, MD, director of the USC Clinical Diabetes Programs.

“This is the deal: The side effects are real because it’s a gut hormone. It’s increasing the level of something your body already has,” she said. 

But, like Dr. Apovian, Dr. Peters said those side effects can likely be avoided if shots are started at the lowest doses and gradually adjusted up. 

While the average starting dose is .25 milligrams, Dr. Peters said she often starts her patients on about an eighth of that – just “a whiff of a dose.” 

“It’ll take them months to get up to the starting dose, but what’s the rush?” 

Dr. Peters said she also avoids giving diabetes patients the maximum dose, which is 2 milligrams per week for Ozempic (and 2.4 milligrams for Wegovy for weight loss). 

When asked about the drugs’ side effects, Novo Nordisk responded that “GLP-1 receptor agonists are a well-established class of medicines, which have demonstrated long-term safety in clinical trials. The most common adverse reactions, as with all GLP-1 [agonists], are gastrointestinal related.”
 

Is it the drug or the weight loss?

Still, non-gastrointestinal side effects such as hair loss, mood changes, and sunken facial features are reported among semaglutide users across the Internet. While these cases are often anecdotal, they can be very heartfelt.

Celina Horvath Myers, also known as CelinaSpookyBoo, a Canadian YouTuber who took Ozempic for type 2 diabetes, said she began having intense panic attacks and depression after starting the medication. 

“Who I have been these last couple weeks, has probably been the scariest time of my life,” she said on her YouTube channel. 

While severe depression and anxiety are not established side effects of the medication, some people get anhedonia, said W. Scott Butsch, MD, MSc, director of obesity medicine in the Bariatric and Metabolic Institute at Cleveland Clinic. But that could be a natural consequence of lower appetite, he said, given that food gives most people pleasure in the moment.

Many other reported changes come from the weight loss itself, not the medication, said Dr. Butsch.

“These are drugs that change the body’s weight regulatory system,” he said. “When someone loses weight, you get the shrinking of the fat cells, as well as the atrophy of the muscles. This rapid weight loss may give the appearance of one’s face changing.”

For some people, like Ms. Mendenall, the side effects are worth it. For others, like Ms. Carew, they’re intolerable. 

Ms. Carew said she stopped the medication after about 7 months, and gradually worked up to eating solid foods again. 

“It’s the American way, we’ve all got to be thin and beautiful,” she said. “But I feel like it’s very unsafe because we just don’t know how seriously our bodies will react to these things in the long term. People see it as a quick fix, but it comes with risks.”

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

Johnna Mendenall had never been “the skinny friend,” she said, but the demands of motherhood – along with a sedentary desk job – made weight management even more difficult. Worried that family type 2 diabetes would catch up with her, she decided to start Wegovy shots for weight loss.

She was nervous about potential side effects. It took 5 days of staring at the Wegovy pen before she worked up the nerve for her first .25-milligram shot. And sure enough, the side effects came on strong.

“The nausea kicked in,” she said. “When I increased my dose to 1 milligram, I spent the entire night from 10 p.m. to 5 a.m. vomiting. I almost quit that day.”

Ms. Mendenall is among a growing number of people sharing personal stories online about the weight loss medication Wegovy – and similar drugs – delving into their sometimes unpleasant, and potentially gut-wrenching, side effects. 

While gastrointestinal (GI) symptoms seem to be the most common, a laundry list of others has been discussed in the news, on TikTok, and across online forums. Those include “Ozempic face,” or the gaunt look some get after taking the medication, along with hair loss, anxiety, depression, and debilitating fatigue. 

Ms. Mendenall’s primary side effects have been vomiting, fatigue, and severe constipation, but she has also seen some positive changes: The “food noise,” or the urge to eat when she isn’t hungry, is gone. Since her first dose 12 weeks ago, she has gone from 236 pounds to 215. 
 

Warning label

Wegovy’s active ingredient, semaglutide, mimics the role of a natural hormone called glucagonlike peptide–1 (GLP-1), which helps you feel well fed. Semaglutide is used at a lower dose under the brand name Ozempic, which is approved for type 2 diabetes and used off-label for weight loss.  

Both Ozempic and Wegovy come with a warning label for potential side effects, the most common ones being nausea, diarrhea, stomach pain, and vomiting.

With the surging popularity of semaglutide, more people are getting prescriptions through telemedicine companies, forgoing more in-depth consultations, leading to more side effects, said Caroline Apovian, MD, professor of medicine at Harvard Medical School and codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, Boston.

Specialists say starting with low doses and gradually increasing over time helps avoid side effects, but insurance companies often require a faster timeline to continue covering the medication, Dr. Apovian said. 

“Insurance companies are practicing medicine for us by demanding the patient go up in dosage [too quickly],” she explained. 

Ms. Mendenall’s insurance has paid for her Wegovy shots, but without that coverage, she said it would cost her $1,200 per month. 

There are similar medications on the market, such as liraglutide, sold under the name Saxenda. But it is a daily, rather than a weekly, shot and also comes with side effects and has been shown to be less effective. In one clinical trial, the people being studied saw their average body weight over 68 weeks drop by 15.8% with semaglutide, and by 6.4% with liraglutide.

Tirzepatide, branded Mounjaro – a type 2 diabetes drug made by Eli Lilly that may soon gain Food and Drug Administration approval for weight loss – could have fewer side effects. In clinical trials, 44% of those taking semaglutide had nausea and 31% reported diarrhea, compared with 33% and 23% of those taking tirzepatide, although no trial has directly compared the two agents. 
 

Loss of bowel control 

For now, Wegovy and Saxenda are the only GLP-1 agonist shots authorized for weight loss, and their maker, Danish drug company Novo Nordisk, is facing its second shortage of Wegovy amid growing demand. 

Personal stories online about semaglutide range from overwhelmingly positive – just what some need to win a lifelong battle with obesity – to harsh scenarios with potentially long-term health consequences, and everything in between. 

One private community on Reddit is dedicated to a particularly unpleasant side effect: loss of bowel control while sleeping. Others have reported uncontrollable vomiting.

Kimberly Carew of Clearwater, Fla., started on .5 milligrams of Ozempic last year after her rheumatologist and endocrinologist suggested it to treat her type 2 diabetes. She was told it came with the bonus of weight loss, which she was hoping would help with her joint and back pain. 

But after she increased the dose to 1 milligram, her GI symptoms, which started out mild, became unbearable. She couldn’t keep food down, and when she vomited, the food would often come up whole, she said. 

“One night I ate ramen before bed. And the next morning, it came out just as it went down,” said Ms. Carew, 42, a registered mental health counseling intern. “I was getting severe heartburn and could not take a couple bites of food without getting nauseous.”

She also had “sulfur burps,” a side effect discussed by some Ozempic users, causing her to taste rotten egg sometimes.

She was diagnosed with gastroparesis. Some types of gastroparesis can be resolved by discontinuing GLP-1 medications, as referenced in two case reports in the Journal of Investigative Medicine. 
 

Gut hormone

GI symptoms are most common with semaglutide because the hormone it imitates, GLP-1, is secreted by cells in the stomach, small intestines, and pancreas, said Anne Peters, MD, director of the USC Clinical Diabetes Programs.

“This is the deal: The side effects are real because it’s a gut hormone. It’s increasing the level of something your body already has,” she said. 

But, like Dr. Apovian, Dr. Peters said those side effects can likely be avoided if shots are started at the lowest doses and gradually adjusted up. 

While the average starting dose is .25 milligrams, Dr. Peters said she often starts her patients on about an eighth of that – just “a whiff of a dose.” 

“It’ll take them months to get up to the starting dose, but what’s the rush?” 

Dr. Peters said she also avoids giving diabetes patients the maximum dose, which is 2 milligrams per week for Ozempic (and 2.4 milligrams for Wegovy for weight loss). 

When asked about the drugs’ side effects, Novo Nordisk responded that “GLP-1 receptor agonists are a well-established class of medicines, which have demonstrated long-term safety in clinical trials. The most common adverse reactions, as with all GLP-1 [agonists], are gastrointestinal related.”
 

Is it the drug or the weight loss?

Still, non-gastrointestinal side effects such as hair loss, mood changes, and sunken facial features are reported among semaglutide users across the Internet. While these cases are often anecdotal, they can be very heartfelt.

Celina Horvath Myers, also known as CelinaSpookyBoo, a Canadian YouTuber who took Ozempic for type 2 diabetes, said she began having intense panic attacks and depression after starting the medication. 

“Who I have been these last couple weeks, has probably been the scariest time of my life,” she said on her YouTube channel. 

While severe depression and anxiety are not established side effects of the medication, some people get anhedonia, said W. Scott Butsch, MD, MSc, director of obesity medicine in the Bariatric and Metabolic Institute at Cleveland Clinic. But that could be a natural consequence of lower appetite, he said, given that food gives most people pleasure in the moment.

Many other reported changes come from the weight loss itself, not the medication, said Dr. Butsch.

“These are drugs that change the body’s weight regulatory system,” he said. “When someone loses weight, you get the shrinking of the fat cells, as well as the atrophy of the muscles. This rapid weight loss may give the appearance of one’s face changing.”

For some people, like Ms. Mendenall, the side effects are worth it. For others, like Ms. Carew, they’re intolerable. 

Ms. Carew said she stopped the medication after about 7 months, and gradually worked up to eating solid foods again. 

“It’s the American way, we’ve all got to be thin and beautiful,” she said. “But I feel like it’s very unsafe because we just don’t know how seriously our bodies will react to these things in the long term. People see it as a quick fix, but it comes with risks.”

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

Johnna Mendenall had never been “the skinny friend,” she said, but the demands of motherhood – along with a sedentary desk job – made weight management even more difficult. Worried that family type 2 diabetes would catch up with her, she decided to start Wegovy shots for weight loss.

She was nervous about potential side effects. It took 5 days of staring at the Wegovy pen before she worked up the nerve for her first .25-milligram shot. And sure enough, the side effects came on strong.

“The nausea kicked in,” she said. “When I increased my dose to 1 milligram, I spent the entire night from 10 p.m. to 5 a.m. vomiting. I almost quit that day.”

Ms. Mendenall is among a growing number of people sharing personal stories online about the weight loss medication Wegovy – and similar drugs – delving into their sometimes unpleasant, and potentially gut-wrenching, side effects. 

While gastrointestinal (GI) symptoms seem to be the most common, a laundry list of others has been discussed in the news, on TikTok, and across online forums. Those include “Ozempic face,” or the gaunt look some get after taking the medication, along with hair loss, anxiety, depression, and debilitating fatigue. 

Ms. Mendenall’s primary side effects have been vomiting, fatigue, and severe constipation, but she has also seen some positive changes: The “food noise,” or the urge to eat when she isn’t hungry, is gone. Since her first dose 12 weeks ago, she has gone from 236 pounds to 215. 
 

Warning label

Wegovy’s active ingredient, semaglutide, mimics the role of a natural hormone called glucagonlike peptide–1 (GLP-1), which helps you feel well fed. Semaglutide is used at a lower dose under the brand name Ozempic, which is approved for type 2 diabetes and used off-label for weight loss.  

Both Ozempic and Wegovy come with a warning label for potential side effects, the most common ones being nausea, diarrhea, stomach pain, and vomiting.

With the surging popularity of semaglutide, more people are getting prescriptions through telemedicine companies, forgoing more in-depth consultations, leading to more side effects, said Caroline Apovian, MD, professor of medicine at Harvard Medical School and codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, Boston.

Specialists say starting with low doses and gradually increasing over time helps avoid side effects, but insurance companies often require a faster timeline to continue covering the medication, Dr. Apovian said. 

“Insurance companies are practicing medicine for us by demanding the patient go up in dosage [too quickly],” she explained. 

Ms. Mendenall’s insurance has paid for her Wegovy shots, but without that coverage, she said it would cost her $1,200 per month. 

There are similar medications on the market, such as liraglutide, sold under the name Saxenda. But it is a daily, rather than a weekly, shot and also comes with side effects and has been shown to be less effective. In one clinical trial, the people being studied saw their average body weight over 68 weeks drop by 15.8% with semaglutide, and by 6.4% with liraglutide.

Tirzepatide, branded Mounjaro – a type 2 diabetes drug made by Eli Lilly that may soon gain Food and Drug Administration approval for weight loss – could have fewer side effects. In clinical trials, 44% of those taking semaglutide had nausea and 31% reported diarrhea, compared with 33% and 23% of those taking tirzepatide, although no trial has directly compared the two agents. 
 

Loss of bowel control 

For now, Wegovy and Saxenda are the only GLP-1 agonist shots authorized for weight loss, and their maker, Danish drug company Novo Nordisk, is facing its second shortage of Wegovy amid growing demand. 

Personal stories online about semaglutide range from overwhelmingly positive – just what some need to win a lifelong battle with obesity – to harsh scenarios with potentially long-term health consequences, and everything in between. 

One private community on Reddit is dedicated to a particularly unpleasant side effect: loss of bowel control while sleeping. Others have reported uncontrollable vomiting.

Kimberly Carew of Clearwater, Fla., started on .5 milligrams of Ozempic last year after her rheumatologist and endocrinologist suggested it to treat her type 2 diabetes. She was told it came with the bonus of weight loss, which she was hoping would help with her joint and back pain. 

But after she increased the dose to 1 milligram, her GI symptoms, which started out mild, became unbearable. She couldn’t keep food down, and when she vomited, the food would often come up whole, she said. 

“One night I ate ramen before bed. And the next morning, it came out just as it went down,” said Ms. Carew, 42, a registered mental health counseling intern. “I was getting severe heartburn and could not take a couple bites of food without getting nauseous.”

She also had “sulfur burps,” a side effect discussed by some Ozempic users, causing her to taste rotten egg sometimes.

She was diagnosed with gastroparesis. Some types of gastroparesis can be resolved by discontinuing GLP-1 medications, as referenced in two case reports in the Journal of Investigative Medicine. 
 

Gut hormone

GI symptoms are most common with semaglutide because the hormone it imitates, GLP-1, is secreted by cells in the stomach, small intestines, and pancreas, said Anne Peters, MD, director of the USC Clinical Diabetes Programs.

“This is the deal: The side effects are real because it’s a gut hormone. It’s increasing the level of something your body already has,” she said. 

But, like Dr. Apovian, Dr. Peters said those side effects can likely be avoided if shots are started at the lowest doses and gradually adjusted up. 

While the average starting dose is .25 milligrams, Dr. Peters said she often starts her patients on about an eighth of that – just “a whiff of a dose.” 

“It’ll take them months to get up to the starting dose, but what’s the rush?” 

Dr. Peters said she also avoids giving diabetes patients the maximum dose, which is 2 milligrams per week for Ozempic (and 2.4 milligrams for Wegovy for weight loss). 

When asked about the drugs’ side effects, Novo Nordisk responded that “GLP-1 receptor agonists are a well-established class of medicines, which have demonstrated long-term safety in clinical trials. The most common adverse reactions, as with all GLP-1 [agonists], are gastrointestinal related.”
 

Is it the drug or the weight loss?

Still, non-gastrointestinal side effects such as hair loss, mood changes, and sunken facial features are reported among semaglutide users across the Internet. While these cases are often anecdotal, they can be very heartfelt.

Celina Horvath Myers, also known as CelinaSpookyBoo, a Canadian YouTuber who took Ozempic for type 2 diabetes, said she began having intense panic attacks and depression after starting the medication. 

“Who I have been these last couple weeks, has probably been the scariest time of my life,” she said on her YouTube channel. 

While severe depression and anxiety are not established side effects of the medication, some people get anhedonia, said W. Scott Butsch, MD, MSc, director of obesity medicine in the Bariatric and Metabolic Institute at Cleveland Clinic. But that could be a natural consequence of lower appetite, he said, given that food gives most people pleasure in the moment.

Many other reported changes come from the weight loss itself, not the medication, said Dr. Butsch.

“These are drugs that change the body’s weight regulatory system,” he said. “When someone loses weight, you get the shrinking of the fat cells, as well as the atrophy of the muscles. This rapid weight loss may give the appearance of one’s face changing.”

For some people, like Ms. Mendenall, the side effects are worth it. For others, like Ms. Carew, they’re intolerable. 

Ms. Carew said she stopped the medication after about 7 months, and gradually worked up to eating solid foods again. 

“It’s the American way, we’ve all got to be thin and beautiful,” she said. “But I feel like it’s very unsafe because we just don’t know how seriously our bodies will react to these things in the long term. People see it as a quick fix, but it comes with risks.”

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

A simple measurement – the cardiorespiratory optimal point (COP) – could predict how long someone will live or the severity of their heart failure, according to clinicians who champion the assessment. The COP is easier to obtain than cardiorespiratory measures that require people to exercise to their limit, advocates say; rather than running full speed, someone can walk or lightly jog on a treadmill, with a COP value obtained easily. 
 

But other clinicians argue that maximal exercise tests have many prognostic benefits, and that physicians should do everything in their power to push patients to exercise as hard as possible. In particular, the VO₂ max test captures the maximum amount of oxygen someone uses when exercising at their capacity and is the preferred method for measuring cardiovascular endurance.

The COP is a measure of the minimum number of liters of air during breathing required to move one liter of oxygen through the bloodstream. The lower the COP the better, because this means that someone is working less strenuously than someone else to transport the same amount of oxygen, denoting a more efficient interaction between their heart and lungs.

The COP for a fit person might be 15, about 20-25 for a healthy person, and 35 for someone with heart failure, according to Claudio Gil Araújo, MD, PhD, director of research and education at CLINIMEX, an exercise medicine clinic in Rio de Janeiro.

“Max VO₂ is very important, that’s indisputable. But when do you use max VO₂ in your daily life? Never,” Dr. Araújo said. But almost anyone can generate a COP.
 

Emerging uses for the COP

“I can put someone on the treadmill or bike, and after 3 or 4 minutes I have the COP. It’s like a walking pace,” Dr. Araújo said. Yet the values are obtained with roughly half the effort as VO₂ max. Other clinicians argue exercising to the limits of endurance offers unique clinical insights.

“We should do everything in our power to exercise our patients to maximum. How long a patient is able to go is really important,” said Anu Lala, MD, a cardiologist who specializes in heart failure treatment at Mount Sinai Hospital in New York. A full-capacity exercise test gives useful insights into someone’s heart rate, heart rate recovery, blood pressure, and ECG response to vigorous exercise, Dr. Lala added, all of which are important clues to someone’s overall health.

In 2012 Dr. Araújo coauthored a study that first defined the COP, which is calculated by measuring expired gasses people produce while gently exercising, perhaps to the point where they begin to perspire, and then dividing their breathing capacity by their oxygen uptake every minute. The lowest value obtained during any exercise session is the COP.

Various studies show that higher COP values are associated with more severe heart lesions in patients with congenital heart disease; higher levels of mortality in seemingly healthy male adults; and with worse prognoses in patients with heart failure. These studies all appeared within the last 7 months.

The mortality study, which Dr. Araújo coauthored, compared COP in more than 3,000 U.S. men and women who completed an exercise test from 1973 to 2018 and were tracked for an average of 23 years. Although COP was introduced as an assessment in 2012, calculating the value from tests prior to that date was possible because those tests had captured the relevant breathing rate and oxygen uptake. In males aged 18-85 years, a worse COP was significantly associated with an increased risk for earlier death. This finding did not hold for females, however; Dr. Araújo noted that more research is needed to understand the discrepancy in COP’s predictive power by sex.

In the heart failure study, everyone enrolled had heart failure and completed a COP test. People with the worse COPs also had the worst symptoms of heart failure, but completing an exercise rehabilitation program improved COP values when researchers measured them again. Dr. Araújo was also part of this study, based in the Netherlands.

“I think the COP could become a novel parameter in clinical care,” for most people, said Thijs Eijsvogels, PhD, an exercise physiologist at Radboud University in Nijmegen, the Netherlands, and the senior author of the heart failure study. That said, Dr. Eijsvogels said elite athletes will always be more interested in measuring VO₂ max.

Dr. Lala agreed that tests such as the COP have some value. Her own work has shown that measuring the efficiency of someone’s breathing patterns for exhaling carbon dioxide, which can also be done without making people exercise full strength, has prognostic value for patients with advanced heart failure. Even so, she said she would like to see maximal effort tests used as much as possible.

“I worry about saying we’re going to settle for a parameter that can be achieved at 50% of peak VO₂ and then we don’t exercise our patients,” Dr. Lala said.

Dr. Araújo said he plans to continue to measure VO₂ max but he believes COP has utility – even for elite athletes. One of his patients is a frequent Ironman competitor who competes well despite having a solid but not amazing VO₂ max level. But her COP is quite low, Dr. Araújo said, which to him suggests an especially efficient interaction between her respiratory and cardiovascular systems.

“We have a new player in the game,” Dr. Araújo said.

The sources in this study report no relevant financial relationships.

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

A simple measurement – the cardiorespiratory optimal point (COP) – could predict how long someone will live or the severity of their heart failure, according to clinicians who champion the assessment. The COP is easier to obtain than cardiorespiratory measures that require people to exercise to their limit, advocates say; rather than running full speed, someone can walk or lightly jog on a treadmill, with a COP value obtained easily. 
 

But other clinicians argue that maximal exercise tests have many prognostic benefits, and that physicians should do everything in their power to push patients to exercise as hard as possible. In particular, the VO₂ max test captures the maximum amount of oxygen someone uses when exercising at their capacity and is the preferred method for measuring cardiovascular endurance.

The COP is a measure of the minimum number of liters of air during breathing required to move one liter of oxygen through the bloodstream. The lower the COP the better, because this means that someone is working less strenuously than someone else to transport the same amount of oxygen, denoting a more efficient interaction between their heart and lungs.

The COP for a fit person might be 15, about 20-25 for a healthy person, and 35 for someone with heart failure, according to Claudio Gil Araújo, MD, PhD, director of research and education at CLINIMEX, an exercise medicine clinic in Rio de Janeiro.

“Max VO₂ is very important, that’s indisputable. But when do you use max VO₂ in your daily life? Never,” Dr. Araújo said. But almost anyone can generate a COP.
 

Emerging uses for the COP

“I can put someone on the treadmill or bike, and after 3 or 4 minutes I have the COP. It’s like a walking pace,” Dr. Araújo said. Yet the values are obtained with roughly half the effort as VO₂ max. Other clinicians argue exercising to the limits of endurance offers unique clinical insights.

“We should do everything in our power to exercise our patients to maximum. How long a patient is able to go is really important,” said Anu Lala, MD, a cardiologist who specializes in heart failure treatment at Mount Sinai Hospital in New York. A full-capacity exercise test gives useful insights into someone’s heart rate, heart rate recovery, blood pressure, and ECG response to vigorous exercise, Dr. Lala added, all of which are important clues to someone’s overall health.

In 2012 Dr. Araújo coauthored a study that first defined the COP, which is calculated by measuring expired gasses people produce while gently exercising, perhaps to the point where they begin to perspire, and then dividing their breathing capacity by their oxygen uptake every minute. The lowest value obtained during any exercise session is the COP.

Various studies show that higher COP values are associated with more severe heart lesions in patients with congenital heart disease; higher levels of mortality in seemingly healthy male adults; and with worse prognoses in patients with heart failure. These studies all appeared within the last 7 months.

The mortality study, which Dr. Araújo coauthored, compared COP in more than 3,000 U.S. men and women who completed an exercise test from 1973 to 2018 and were tracked for an average of 23 years. Although COP was introduced as an assessment in 2012, calculating the value from tests prior to that date was possible because those tests had captured the relevant breathing rate and oxygen uptake. In males aged 18-85 years, a worse COP was significantly associated with an increased risk for earlier death. This finding did not hold for females, however; Dr. Araújo noted that more research is needed to understand the discrepancy in COP’s predictive power by sex.

In the heart failure study, everyone enrolled had heart failure and completed a COP test. People with the worse COPs also had the worst symptoms of heart failure, but completing an exercise rehabilitation program improved COP values when researchers measured them again. Dr. Araújo was also part of this study, based in the Netherlands.

“I think the COP could become a novel parameter in clinical care,” for most people, said Thijs Eijsvogels, PhD, an exercise physiologist at Radboud University in Nijmegen, the Netherlands, and the senior author of the heart failure study. That said, Dr. Eijsvogels said elite athletes will always be more interested in measuring VO₂ max.

Dr. Lala agreed that tests such as the COP have some value. Her own work has shown that measuring the efficiency of someone’s breathing patterns for exhaling carbon dioxide, which can also be done without making people exercise full strength, has prognostic value for patients with advanced heart failure. Even so, she said she would like to see maximal effort tests used as much as possible.

“I worry about saying we’re going to settle for a parameter that can be achieved at 50% of peak VO₂ and then we don’t exercise our patients,” Dr. Lala said.

Dr. Araújo said he plans to continue to measure VO₂ max but he believes COP has utility – even for elite athletes. One of his patients is a frequent Ironman competitor who competes well despite having a solid but not amazing VO₂ max level. But her COP is quite low, Dr. Araújo said, which to him suggests an especially efficient interaction between her respiratory and cardiovascular systems.

“We have a new player in the game,” Dr. Araújo said.

The sources in this study report no relevant financial relationships.

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

A simple measurement – the cardiorespiratory optimal point (COP) – could predict how long someone will live or the severity of their heart failure, according to clinicians who champion the assessment. The COP is easier to obtain than cardiorespiratory measures that require people to exercise to their limit, advocates say; rather than running full speed, someone can walk or lightly jog on a treadmill, with a COP value obtained easily. 
 

But other clinicians argue that maximal exercise tests have many prognostic benefits, and that physicians should do everything in their power to push patients to exercise as hard as possible. In particular, the VO₂ max test captures the maximum amount of oxygen someone uses when exercising at their capacity and is the preferred method for measuring cardiovascular endurance.

The COP is a measure of the minimum number of liters of air during breathing required to move one liter of oxygen through the bloodstream. The lower the COP the better, because this means that someone is working less strenuously than someone else to transport the same amount of oxygen, denoting a more efficient interaction between their heart and lungs.

The COP for a fit person might be 15, about 20-25 for a healthy person, and 35 for someone with heart failure, according to Claudio Gil Araújo, MD, PhD, director of research and education at CLINIMEX, an exercise medicine clinic in Rio de Janeiro.

“Max VO₂ is very important, that’s indisputable. But when do you use max VO₂ in your daily life? Never,” Dr. Araújo said. But almost anyone can generate a COP.
 

Emerging uses for the COP

“I can put someone on the treadmill or bike, and after 3 or 4 minutes I have the COP. It’s like a walking pace,” Dr. Araújo said. Yet the values are obtained with roughly half the effort as VO₂ max. Other clinicians argue exercising to the limits of endurance offers unique clinical insights.

“We should do everything in our power to exercise our patients to maximum. How long a patient is able to go is really important,” said Anu Lala, MD, a cardiologist who specializes in heart failure treatment at Mount Sinai Hospital in New York. A full-capacity exercise test gives useful insights into someone’s heart rate, heart rate recovery, blood pressure, and ECG response to vigorous exercise, Dr. Lala added, all of which are important clues to someone’s overall health.

In 2012 Dr. Araújo coauthored a study that first defined the COP, which is calculated by measuring expired gasses people produce while gently exercising, perhaps to the point where they begin to perspire, and then dividing their breathing capacity by their oxygen uptake every minute. The lowest value obtained during any exercise session is the COP.

Various studies show that higher COP values are associated with more severe heart lesions in patients with congenital heart disease; higher levels of mortality in seemingly healthy male adults; and with worse prognoses in patients with heart failure. These studies all appeared within the last 7 months.

The mortality study, which Dr. Araújo coauthored, compared COP in more than 3,000 U.S. men and women who completed an exercise test from 1973 to 2018 and were tracked for an average of 23 years. Although COP was introduced as an assessment in 2012, calculating the value from tests prior to that date was possible because those tests had captured the relevant breathing rate and oxygen uptake. In males aged 18-85 years, a worse COP was significantly associated with an increased risk for earlier death. This finding did not hold for females, however; Dr. Araújo noted that more research is needed to understand the discrepancy in COP’s predictive power by sex.

In the heart failure study, everyone enrolled had heart failure and completed a COP test. People with the worse COPs also had the worst symptoms of heart failure, but completing an exercise rehabilitation program improved COP values when researchers measured them again. Dr. Araújo was also part of this study, based in the Netherlands.

“I think the COP could become a novel parameter in clinical care,” for most people, said Thijs Eijsvogels, PhD, an exercise physiologist at Radboud University in Nijmegen, the Netherlands, and the senior author of the heart failure study. That said, Dr. Eijsvogels said elite athletes will always be more interested in measuring VO₂ max.

Dr. Lala agreed that tests such as the COP have some value. Her own work has shown that measuring the efficiency of someone’s breathing patterns for exhaling carbon dioxide, which can also be done without making people exercise full strength, has prognostic value for patients with advanced heart failure. Even so, she said she would like to see maximal effort tests used as much as possible.

“I worry about saying we’re going to settle for a parameter that can be achieved at 50% of peak VO₂ and then we don’t exercise our patients,” Dr. Lala said.

Dr. Araújo said he plans to continue to measure VO₂ max but he believes COP has utility – even for elite athletes. One of his patients is a frequent Ironman competitor who competes well despite having a solid but not amazing VO₂ max level. But her COP is quite low, Dr. Araújo said, which to him suggests an especially efficient interaction between her respiratory and cardiovascular systems.

“We have a new player in the game,” Dr. Araújo said.

The sources in this study report no relevant financial relationships.

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

MILAN – Treatment of systemic lupus erythematosus with biologics may enable steroid tapering while ensuring the achievement of remission or low disease activity in more patients with fewer flares and less organ damage, as well as leading to better responses if used early, according to the latest recommendations on the management of SLE from the European Alliance of Associations for Rheumatology (EULAR).

Dimitrios Boumpas, MD, president of the Athens Medical Society and chair of the European Task force on SLE, presented the recommendations at the annual European Congress of Rheumatology. “Although steroids save lives, it is at the expense of excessive collateral damage. They are better for short-term use as a rescue or bridging therapy but may be used in some patients at 5 mg/day of prednisone or less, rather than the previous 7.5 mg/day,” he emphasized.

The 2023 recommendations cover new treatment strategies with more ambitious goals, new data on adverse effects of chronic glucocorticoid use, and newly approved agents and combination therapies.

“Most importantly, we sourced help from experts from all over the world,” said Dr. Boumpas, describing the task force that included 35 rheumatologists, 5 nephrologists, 2 methodologists, 2 patient representatives, and 2 fellows, all brought together from across Europe, North America, Asia, and Australia.

Over 7,000 papers were reviewed, with 437 included in the systematic literature review to inform the updated recommendations.

Session moderator Robert Landewé, MD, PhD, professor of clinical immunology and rheumatology at the University of Amsterdam, said that “the underlying heterogeneity and multisystem involvement of SLE can make it difficult to demonstrate and know which drugs work in the condition. However, these latest recommendations should encourage greater confidence to taper steroids early on and perhaps consider new biologic drugs, so that more patients can achieve better results sooner to prevent flares and organ damage, improve prognosis, and enhance their quality of life.”

Dr. Boumpas provided a summary of the overarching principles that guide the recommendations. These say that SLE requires multidisciplinary individualized management; disease activity should be assessed at each visit; nonpharmacologic interventions such as sun protection, smoking cessation, and following a healthy diet are all important for improving long-term outcomes; pharmacologic interventions are to be directed by patient characteristics, type and severity of organ involvement, treatment-related harms, and patient preferences, among other factors; and early SLE diagnosis is essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.

Referring to each recommendation statement in turn, Dr. Boumpas provided a detailed description of each, and highlighted any changes since the 2019 recommendations.
 

Hydroxychloroquine, glucocorticoids as bridging therapy, and biologics

Referring to statement 1, Dr. Boumpas reported that hydroxychloroquine should be a first-line therapy at a dose of 5 mg/kg, but this dose should be individualized based on risk of flare and retinal toxicity. “There was some discussion about monitoring blood levels, but this was to ensure adherence only,” said Dr. Boumpas.

Continuing to statement 2, he added, “here is one change. With chronic use of glucocorticoids, the maintenance dose is 5 mg/day or less or prednisone equivalent. This pertains to both new onset and relapsing disease.” Previous recommendations advised a maintenance dose of 7.5 mg/day or less.

But he pointed out that “we are discussing using glucocorticoids in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of glucocorticoids and only use them for 3 months, and to do this we need to use glucocorticoid-sparing strategies.”

This led to statement 3, which refers to glucocorticoid-sparing strategies. Dr. Boumpas explained that, in patients who are not responding to hydroxychloroquine or unable to reduce glucocorticoids further during chronic use, add immunosuppressive agents, such as methotrexate and/or biologics (for example, belimumab [Benlysta] or anifrolumab [Saphnelo]).

“To allow flexibility for patients and clinicians, it isn’t necessary to use DMARDs [disease-modifying antirheumatic drugs] first if you prefer biologics,” he continued. “We are becoming more liberal with the use of biologics because there are new data that confirm the efficacy of belimumab in extrarenal SLE, plus good data with 3-year extension with anifrolumab.”

Statement 4 says that for patients with organ- or life-threatening disease, intravenous cyclophosphamide, “our old friend,” should be considered, while in refractory cases, rituximab may be considered, Dr. Boumpas said. “It’s okay to use cyclophosphamide. It isn’t a sin.”

Statement 5 refers to skin disease, and Dr. Boumpas explained that good data suggested that biologics help, including both belimumab and anifrolumab.

Nothing has changed with statement 6 concerning neuropsychiatric lupus, said Dr. Boumpas. “Glucocorticoids, immunosuppressive, and antithrombotic therapies should be considered.”

Regarding hematologic disease (statement 7), he said, “the new kid on the block is MMF [mycophenolate mofetil]. For acute treatment, still use the same drugs, including rituximab, but for maintenance you may use rituximab, azathioprine, MMF, or cyclosporine.”
 

Lupus nephritis

Turning to what Dr. Boumpas described as the “reason you had all come here, and what you had been waiting for ... what’s changing with lupus nephritis?” he said.

Statement 8 describes initial therapy in active lupus nephritis. Dr. Boumpas said that low-dose, intravenous cyclophosphamide or mycophenolate should be considered, but also that belimumab or a calcineurin inhibitor (CNI) should be considered at the start. The changes were based on two successful phase 3 trials of belimumab and voclosporin, with belimumab being associated with a reduced flare rate and estimated glomerular filtration rate (eGFR).

“Changes from 2019 include that there is no distinction between classes III/IV and V, which is heretical,” he stressed. Belimumab and CNIs/voclosporin should be considered in all patents as an add-on therapy from the start. “Lupus nephritis has high morbidity, and it’s difficult to predict outcomes at the beginning, but there are clear benefits of add-on therapies. CNIs, although they can be used for all patients, might be more appropriate for membranous or nephrotic-range proteinuria.”

He went on to announce that the “million-dollar question” was whether to use belimumab or voclosporin (or other CNIs), and that this was “a question of gentle, compared with forceful, power and collateral damage.

“For me, voclosporin works very fast, but you worry about side effects, while belimumab is gentle and the response is sustained, preventing flares and organ damage,” he said, adding that “our expert panel discussions showed that nephrologists were more eager to support steroid-free regimens.”

Moving on to statement 9, Dr. Boumpas explained that after initial therapy and renal response, subsequent therapy should continue for at least 3 years. If treated with MMF alone or in combination with belimumab, then these drugs should continue. However, MMF should replace cyclophosphamide if the latter is used initially.

Regarding treat-to-target in lupus nephritis, he said that EULAR now advises to aim for a 25% drop in urine protein/creatinine ratio by 3 months, a 50% drop by 6 months, and a UPCR of less than 0.5-0.7, plus normal eGFR, by 12 months, Dr. Boumpas said.

Statement 10 advises considering high-dose intravenous cyclophosphamide in combination with pulse intravenous methylprednisolone for patients at high risk of renal failure.
 

Tapering drugs in sustained remission, managing antiphospholipid syndrome, giving immunizations

Statement 11 suggests to consider tapering immunosuppressive agents and glucocorticoids in patients achieving sustained remission, starting with glucocorticoids first.

There was no change to statement 12, which recommends that thrombotic antiphospholipid syndrome associated with SLE be treated with long-term vitamin K antagonists.

Statement 13 addresses immunizations and adjunct therapies. In addition to conventional immunizations, Dr. Boumpas said that renoprotection should receive attention in case of proteinuria and/or hypertension.

“With [sodium-glucose cotransporter 2] inhibitors, it’s a bit early. They’re promising, and you may consider them, although there are no data for patients with eGFR below 60 mL/min per 1.73 m²,” he remarked, completing his detailed discussion of the updated recommendations.

Dr. Boumpas reported no relevant financial relationships. Dr. Landewé served as past chair of EULAR’s Quality of Care Committee, which develops recommendations.

MILAN – Treatment of systemic lupus erythematosus with biologics may enable steroid tapering while ensuring the achievement of remission or low disease activity in more patients with fewer flares and less organ damage, as well as leading to better responses if used early, according to the latest recommendations on the management of SLE from the European Alliance of Associations for Rheumatology (EULAR).

Dimitrios Boumpas, MD, president of the Athens Medical Society and chair of the European Task force on SLE, presented the recommendations at the annual European Congress of Rheumatology. “Although steroids save lives, it is at the expense of excessive collateral damage. They are better for short-term use as a rescue or bridging therapy but may be used in some patients at 5 mg/day of prednisone or less, rather than the previous 7.5 mg/day,” he emphasized.

The 2023 recommendations cover new treatment strategies with more ambitious goals, new data on adverse effects of chronic glucocorticoid use, and newly approved agents and combination therapies.

“Most importantly, we sourced help from experts from all over the world,” said Dr. Boumpas, describing the task force that included 35 rheumatologists, 5 nephrologists, 2 methodologists, 2 patient representatives, and 2 fellows, all brought together from across Europe, North America, Asia, and Australia.

Over 7,000 papers were reviewed, with 437 included in the systematic literature review to inform the updated recommendations.

Session moderator Robert Landewé, MD, PhD, professor of clinical immunology and rheumatology at the University of Amsterdam, said that “the underlying heterogeneity and multisystem involvement of SLE can make it difficult to demonstrate and know which drugs work in the condition. However, these latest recommendations should encourage greater confidence to taper steroids early on and perhaps consider new biologic drugs, so that more patients can achieve better results sooner to prevent flares and organ damage, improve prognosis, and enhance their quality of life.”

Dr. Boumpas provided a summary of the overarching principles that guide the recommendations. These say that SLE requires multidisciplinary individualized management; disease activity should be assessed at each visit; nonpharmacologic interventions such as sun protection, smoking cessation, and following a healthy diet are all important for improving long-term outcomes; pharmacologic interventions are to be directed by patient characteristics, type and severity of organ involvement, treatment-related harms, and patient preferences, among other factors; and early SLE diagnosis is essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.

Referring to each recommendation statement in turn, Dr. Boumpas provided a detailed description of each, and highlighted any changes since the 2019 recommendations.
 

Hydroxychloroquine, glucocorticoids as bridging therapy, and biologics

Referring to statement 1, Dr. Boumpas reported that hydroxychloroquine should be a first-line therapy at a dose of 5 mg/kg, but this dose should be individualized based on risk of flare and retinal toxicity. “There was some discussion about monitoring blood levels, but this was to ensure adherence only,” said Dr. Boumpas.

Continuing to statement 2, he added, “here is one change. With chronic use of glucocorticoids, the maintenance dose is 5 mg/day or less or prednisone equivalent. This pertains to both new onset and relapsing disease.” Previous recommendations advised a maintenance dose of 7.5 mg/day or less.

But he pointed out that “we are discussing using glucocorticoids in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of glucocorticoids and only use them for 3 months, and to do this we need to use glucocorticoid-sparing strategies.”

This led to statement 3, which refers to glucocorticoid-sparing strategies. Dr. Boumpas explained that, in patients who are not responding to hydroxychloroquine or unable to reduce glucocorticoids further during chronic use, add immunosuppressive agents, such as methotrexate and/or biologics (for example, belimumab [Benlysta] or anifrolumab [Saphnelo]).

“To allow flexibility for patients and clinicians, it isn’t necessary to use DMARDs [disease-modifying antirheumatic drugs] first if you prefer biologics,” he continued. “We are becoming more liberal with the use of biologics because there are new data that confirm the efficacy of belimumab in extrarenal SLE, plus good data with 3-year extension with anifrolumab.”

Statement 4 says that for patients with organ- or life-threatening disease, intravenous cyclophosphamide, “our old friend,” should be considered, while in refractory cases, rituximab may be considered, Dr. Boumpas said. “It’s okay to use cyclophosphamide. It isn’t a sin.”

Statement 5 refers to skin disease, and Dr. Boumpas explained that good data suggested that biologics help, including both belimumab and anifrolumab.

Nothing has changed with statement 6 concerning neuropsychiatric lupus, said Dr. Boumpas. “Glucocorticoids, immunosuppressive, and antithrombotic therapies should be considered.”

Regarding hematologic disease (statement 7), he said, “the new kid on the block is MMF [mycophenolate mofetil]. For acute treatment, still use the same drugs, including rituximab, but for maintenance you may use rituximab, azathioprine, MMF, or cyclosporine.”
 

Lupus nephritis

Turning to what Dr. Boumpas described as the “reason you had all come here, and what you had been waiting for ... what’s changing with lupus nephritis?” he said.

Statement 8 describes initial therapy in active lupus nephritis. Dr. Boumpas said that low-dose, intravenous cyclophosphamide or mycophenolate should be considered, but also that belimumab or a calcineurin inhibitor (CNI) should be considered at the start. The changes were based on two successful phase 3 trials of belimumab and voclosporin, with belimumab being associated with a reduced flare rate and estimated glomerular filtration rate (eGFR).

“Changes from 2019 include that there is no distinction between classes III/IV and V, which is heretical,” he stressed. Belimumab and CNIs/voclosporin should be considered in all patents as an add-on therapy from the start. “Lupus nephritis has high morbidity, and it’s difficult to predict outcomes at the beginning, but there are clear benefits of add-on therapies. CNIs, although they can be used for all patients, might be more appropriate for membranous or nephrotic-range proteinuria.”

He went on to announce that the “million-dollar question” was whether to use belimumab or voclosporin (or other CNIs), and that this was “a question of gentle, compared with forceful, power and collateral damage.

“For me, voclosporin works very fast, but you worry about side effects, while belimumab is gentle and the response is sustained, preventing flares and organ damage,” he said, adding that “our expert panel discussions showed that nephrologists were more eager to support steroid-free regimens.”

Moving on to statement 9, Dr. Boumpas explained that after initial therapy and renal response, subsequent therapy should continue for at least 3 years. If treated with MMF alone or in combination with belimumab, then these drugs should continue. However, MMF should replace cyclophosphamide if the latter is used initially.

Regarding treat-to-target in lupus nephritis, he said that EULAR now advises to aim for a 25% drop in urine protein/creatinine ratio by 3 months, a 50% drop by 6 months, and a UPCR of less than 0.5-0.7, plus normal eGFR, by 12 months, Dr. Boumpas said.

Statement 10 advises considering high-dose intravenous cyclophosphamide in combination with pulse intravenous methylprednisolone for patients at high risk of renal failure.
 

Tapering drugs in sustained remission, managing antiphospholipid syndrome, giving immunizations

Statement 11 suggests to consider tapering immunosuppressive agents and glucocorticoids in patients achieving sustained remission, starting with glucocorticoids first.

There was no change to statement 12, which recommends that thrombotic antiphospholipid syndrome associated with SLE be treated with long-term vitamin K antagonists.

Statement 13 addresses immunizations and adjunct therapies. In addition to conventional immunizations, Dr. Boumpas said that renoprotection should receive attention in case of proteinuria and/or hypertension.

“With [sodium-glucose cotransporter 2] inhibitors, it’s a bit early. They’re promising, and you may consider them, although there are no data for patients with eGFR below 60 mL/min per 1.73 m²,” he remarked, completing his detailed discussion of the updated recommendations.

Dr. Boumpas reported no relevant financial relationships. Dr. Landewé served as past chair of EULAR’s Quality of Care Committee, which develops recommendations.

MILAN – Treatment of systemic lupus erythematosus with biologics may enable steroid tapering while ensuring the achievement of remission or low disease activity in more patients with fewer flares and less organ damage, as well as leading to better responses if used early, according to the latest recommendations on the management of SLE from the European Alliance of Associations for Rheumatology (EULAR).

Dimitrios Boumpas, MD, president of the Athens Medical Society and chair of the European Task force on SLE, presented the recommendations at the annual European Congress of Rheumatology. “Although steroids save lives, it is at the expense of excessive collateral damage. They are better for short-term use as a rescue or bridging therapy but may be used in some patients at 5 mg/day of prednisone or less, rather than the previous 7.5 mg/day,” he emphasized.

The 2023 recommendations cover new treatment strategies with more ambitious goals, new data on adverse effects of chronic glucocorticoid use, and newly approved agents and combination therapies.

“Most importantly, we sourced help from experts from all over the world,” said Dr. Boumpas, describing the task force that included 35 rheumatologists, 5 nephrologists, 2 methodologists, 2 patient representatives, and 2 fellows, all brought together from across Europe, North America, Asia, and Australia.

Over 7,000 papers were reviewed, with 437 included in the systematic literature review to inform the updated recommendations.

Session moderator Robert Landewé, MD, PhD, professor of clinical immunology and rheumatology at the University of Amsterdam, said that “the underlying heterogeneity and multisystem involvement of SLE can make it difficult to demonstrate and know which drugs work in the condition. However, these latest recommendations should encourage greater confidence to taper steroids early on and perhaps consider new biologic drugs, so that more patients can achieve better results sooner to prevent flares and organ damage, improve prognosis, and enhance their quality of life.”

Dr. Boumpas provided a summary of the overarching principles that guide the recommendations. These say that SLE requires multidisciplinary individualized management; disease activity should be assessed at each visit; nonpharmacologic interventions such as sun protection, smoking cessation, and following a healthy diet are all important for improving long-term outcomes; pharmacologic interventions are to be directed by patient characteristics, type and severity of organ involvement, treatment-related harms, and patient preferences, among other factors; and early SLE diagnosis is essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.

Referring to each recommendation statement in turn, Dr. Boumpas provided a detailed description of each, and highlighted any changes since the 2019 recommendations.
 

Hydroxychloroquine, glucocorticoids as bridging therapy, and biologics

Referring to statement 1, Dr. Boumpas reported that hydroxychloroquine should be a first-line therapy at a dose of 5 mg/kg, but this dose should be individualized based on risk of flare and retinal toxicity. “There was some discussion about monitoring blood levels, but this was to ensure adherence only,” said Dr. Boumpas.

Continuing to statement 2, he added, “here is one change. With chronic use of glucocorticoids, the maintenance dose is 5 mg/day or less or prednisone equivalent. This pertains to both new onset and relapsing disease.” Previous recommendations advised a maintenance dose of 7.5 mg/day or less.

But he pointed out that “we are discussing using glucocorticoids in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of glucocorticoids and only use them for 3 months, and to do this we need to use glucocorticoid-sparing strategies.”

This led to statement 3, which refers to glucocorticoid-sparing strategies. Dr. Boumpas explained that, in patients who are not responding to hydroxychloroquine or unable to reduce glucocorticoids further during chronic use, add immunosuppressive agents, such as methotrexate and/or biologics (for example, belimumab [Benlysta] or anifrolumab [Saphnelo]).

“To allow flexibility for patients and clinicians, it isn’t necessary to use DMARDs [disease-modifying antirheumatic drugs] first if you prefer biologics,” he continued. “We are becoming more liberal with the use of biologics because there are new data that confirm the efficacy of belimumab in extrarenal SLE, plus good data with 3-year extension with anifrolumab.”

Statement 4 says that for patients with organ- or life-threatening disease, intravenous cyclophosphamide, “our old friend,” should be considered, while in refractory cases, rituximab may be considered, Dr. Boumpas said. “It’s okay to use cyclophosphamide. It isn’t a sin.”

Statement 5 refers to skin disease, and Dr. Boumpas explained that good data suggested that biologics help, including both belimumab and anifrolumab.

Nothing has changed with statement 6 concerning neuropsychiatric lupus, said Dr. Boumpas. “Glucocorticoids, immunosuppressive, and antithrombotic therapies should be considered.”

Regarding hematologic disease (statement 7), he said, “the new kid on the block is MMF [mycophenolate mofetil]. For acute treatment, still use the same drugs, including rituximab, but for maintenance you may use rituximab, azathioprine, MMF, or cyclosporine.”
 

Lupus nephritis

Turning to what Dr. Boumpas described as the “reason you had all come here, and what you had been waiting for ... what’s changing with lupus nephritis?” he said.

Statement 8 describes initial therapy in active lupus nephritis. Dr. Boumpas said that low-dose, intravenous cyclophosphamide or mycophenolate should be considered, but also that belimumab or a calcineurin inhibitor (CNI) should be considered at the start. The changes were based on two successful phase 3 trials of belimumab and voclosporin, with belimumab being associated with a reduced flare rate and estimated glomerular filtration rate (eGFR).

“Changes from 2019 include that there is no distinction between classes III/IV and V, which is heretical,” he stressed. Belimumab and CNIs/voclosporin should be considered in all patents as an add-on therapy from the start. “Lupus nephritis has high morbidity, and it’s difficult to predict outcomes at the beginning, but there are clear benefits of add-on therapies. CNIs, although they can be used for all patients, might be more appropriate for membranous or nephrotic-range proteinuria.”

He went on to announce that the “million-dollar question” was whether to use belimumab or voclosporin (or other CNIs), and that this was “a question of gentle, compared with forceful, power and collateral damage.

“For me, voclosporin works very fast, but you worry about side effects, while belimumab is gentle and the response is sustained, preventing flares and organ damage,” he said, adding that “our expert panel discussions showed that nephrologists were more eager to support steroid-free regimens.”

Moving on to statement 9, Dr. Boumpas explained that after initial therapy and renal response, subsequent therapy should continue for at least 3 years. If treated with MMF alone or in combination with belimumab, then these drugs should continue. However, MMF should replace cyclophosphamide if the latter is used initially.

Regarding treat-to-target in lupus nephritis, he said that EULAR now advises to aim for a 25% drop in urine protein/creatinine ratio by 3 months, a 50% drop by 6 months, and a UPCR of less than 0.5-0.7, plus normal eGFR, by 12 months, Dr. Boumpas said.

Statement 10 advises considering high-dose intravenous cyclophosphamide in combination with pulse intravenous methylprednisolone for patients at high risk of renal failure.
 

Tapering drugs in sustained remission, managing antiphospholipid syndrome, giving immunizations

Statement 11 suggests to consider tapering immunosuppressive agents and glucocorticoids in patients achieving sustained remission, starting with glucocorticoids first.

There was no change to statement 12, which recommends that thrombotic antiphospholipid syndrome associated with SLE be treated with long-term vitamin K antagonists.

Statement 13 addresses immunizations and adjunct therapies. In addition to conventional immunizations, Dr. Boumpas said that renoprotection should receive attention in case of proteinuria and/or hypertension.

“With [sodium-glucose cotransporter 2] inhibitors, it’s a bit early. They’re promising, and you may consider them, although there are no data for patients with eGFR below 60 mL/min per 1.73 m²,” he remarked, completing his detailed discussion of the updated recommendations.

Dr. Boumpas reported no relevant financial relationships. Dr. Landewé served as past chair of EULAR’s Quality of Care Committee, which develops recommendations.

A new study suggests that prescriptions for low-dose oral minoxidil soared in the wake of a 2022 New York Times article that highlighted its utility for hair loss.

©herkisi/iStockphoto.com

The weekly rate of first-time low-dose oral minoxidil (LDOM) prescriptions per 10,000 outpatient encounters was “significantly higher 8 weeks after vs. 8 weeks before article publication,” at 0.9 prescriptions, compared with 0.5 per 10,000, wrote the authors of the research letter, published in JAMA Network Open. There was no similar bump for first-time finasteride or hypertension prescriptions, wrote the authors, from Harvard Medical School and Massachusetts General Hospital, Boston, and Truveta, a company that provides EHR data from U.S. health care systems.

The New York Times article noted that LDOM was relatively unknown to patients and doctors – and not approved by the Food and Drug Administration for treating hair loss – but that it was inexpensive, safe, and very effective for many individuals. “The article did not report new research findings or large-scale randomized evidence,” wrote the authors of the JAMA study.

In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said that he was not surprised to see an uptick in prescriptions after the Times article.

He and his colleagues were curious as to whether the article might have prompted newfound interest in LDOM. They experienced an uptick at George Washington, which Dr. Friedman thought could have been because he was quoted in the Times story. He and colleagues conducted a national survey of dermatologists asking if more patients had called, emailed, or come in to the office asking about LDOM after the article’s publication. “Over 85% said yes,” Dr. Friedman said in the interview. He and his coauthors also found a huge increase in Google searches for terms such as hair loss, alopecia, and minoxidil in the weeks after the article, he said.

The results are expected to published soon in the Journal of Drugs in Dermatology.

“I think a lot of people know about [LDOM] and it’s certainly has gained a lot more attention and acceptance in recent years,” said Dr. Friedman, but he added that “there’s no question” that the Times article increased interest.

That is not necessarily a bad thing, he said. “With one article, education on a common disease was disseminated worldwide in a way that no one doctor can do,” he said. The article was truthful, evidence-based, and included expert dermatologists, he noted.

“It probably got people who never thought twice about their hair thinning to actually think that there’s hope,” he said, adding that it also likely prompted them to seek care, and, more importantly, “to seek care from the person who should be taking care of this, which is the dermatologist.”

However, the article might also inspire some people to think LDOM can help when it can’t, or they might insist on a prescription when another medication is more appropriate, said Dr. Friedman.

Both he and Dr. Sinclair expect demand for LDOM to continue increasing.

“Word of mouth will drive the next wave of prescriptions,” said Dr. Sinclair. “We are continuing to do work to improve safety, to understand its mechanism of action, and identify ways to improve equity of access to treatment for men and women who are concerned about their hair loss and motivated to treat it,” he said.

Dr. Sinclair and Dr. Friedman report no relevant financial relationships.

A new study suggests that prescriptions for low-dose oral minoxidil soared in the wake of a 2022 New York Times article that highlighted its utility for hair loss.

©herkisi/iStockphoto.com

The weekly rate of first-time low-dose oral minoxidil (LDOM) prescriptions per 10,000 outpatient encounters was “significantly higher 8 weeks after vs. 8 weeks before article publication,” at 0.9 prescriptions, compared with 0.5 per 10,000, wrote the authors of the research letter, published in JAMA Network Open. There was no similar bump for first-time finasteride or hypertension prescriptions, wrote the authors, from Harvard Medical School and Massachusetts General Hospital, Boston, and Truveta, a company that provides EHR data from U.S. health care systems.

The New York Times article noted that LDOM was relatively unknown to patients and doctors – and not approved by the Food and Drug Administration for treating hair loss – but that it was inexpensive, safe, and very effective for many individuals. “The article did not report new research findings or large-scale randomized evidence,” wrote the authors of the JAMA study.

In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said that he was not surprised to see an uptick in prescriptions after the Times article.

He and his colleagues were curious as to whether the article might have prompted newfound interest in LDOM. They experienced an uptick at George Washington, which Dr. Friedman thought could have been because he was quoted in the Times story. He and colleagues conducted a national survey of dermatologists asking if more patients had called, emailed, or come in to the office asking about LDOM after the article’s publication. “Over 85% said yes,” Dr. Friedman said in the interview. He and his coauthors also found a huge increase in Google searches for terms such as hair loss, alopecia, and minoxidil in the weeks after the article, he said.

The results are expected to published soon in the Journal of Drugs in Dermatology.

“I think a lot of people know about [LDOM] and it’s certainly has gained a lot more attention and acceptance in recent years,” said Dr. Friedman, but he added that “there’s no question” that the Times article increased interest.

That is not necessarily a bad thing, he said. “With one article, education on a common disease was disseminated worldwide in a way that no one doctor can do,” he said. The article was truthful, evidence-based, and included expert dermatologists, he noted.

“It probably got people who never thought twice about their hair thinning to actually think that there’s hope,” he said, adding that it also likely prompted them to seek care, and, more importantly, “to seek care from the person who should be taking care of this, which is the dermatologist.”

However, the article might also inspire some people to think LDOM can help when it can’t, or they might insist on a prescription when another medication is more appropriate, said Dr. Friedman.

Both he and Dr. Sinclair expect demand for LDOM to continue increasing.

“Word of mouth will drive the next wave of prescriptions,” said Dr. Sinclair. “We are continuing to do work to improve safety, to understand its mechanism of action, and identify ways to improve equity of access to treatment for men and women who are concerned about their hair loss and motivated to treat it,” he said.

Dr. Sinclair and Dr. Friedman report no relevant financial relationships.

A new study suggests that prescriptions for low-dose oral minoxidil soared in the wake of a 2022 New York Times article that highlighted its utility for hair loss.

©herkisi/iStockphoto.com

The weekly rate of first-time low-dose oral minoxidil (LDOM) prescriptions per 10,000 outpatient encounters was “significantly higher 8 weeks after vs. 8 weeks before article publication,” at 0.9 prescriptions, compared with 0.5 per 10,000, wrote the authors of the research letter, published in JAMA Network Open. There was no similar bump for first-time finasteride or hypertension prescriptions, wrote the authors, from Harvard Medical School and Massachusetts General Hospital, Boston, and Truveta, a company that provides EHR data from U.S. health care systems.

The New York Times article noted that LDOM was relatively unknown to patients and doctors – and not approved by the Food and Drug Administration for treating hair loss – but that it was inexpensive, safe, and very effective for many individuals. “The article did not report new research findings or large-scale randomized evidence,” wrote the authors of the JAMA study.

In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said that he was not surprised to see an uptick in prescriptions after the Times article.

He and his colleagues were curious as to whether the article might have prompted newfound interest in LDOM. They experienced an uptick at George Washington, which Dr. Friedman thought could have been because he was quoted in the Times story. He and colleagues conducted a national survey of dermatologists asking if more patients had called, emailed, or come in to the office asking about LDOM after the article’s publication. “Over 85% said yes,” Dr. Friedman said in the interview. He and his coauthors also found a huge increase in Google searches for terms such as hair loss, alopecia, and minoxidil in the weeks after the article, he said.

The results are expected to published soon in the Journal of Drugs in Dermatology.

“I think a lot of people know about [LDOM] and it’s certainly has gained a lot more attention and acceptance in recent years,” said Dr. Friedman, but he added that “there’s no question” that the Times article increased interest.

That is not necessarily a bad thing, he said. “With one article, education on a common disease was disseminated worldwide in a way that no one doctor can do,” he said. The article was truthful, evidence-based, and included expert dermatologists, he noted.

“It probably got people who never thought twice about their hair thinning to actually think that there’s hope,” he said, adding that it also likely prompted them to seek care, and, more importantly, “to seek care from the person who should be taking care of this, which is the dermatologist.”

However, the article might also inspire some people to think LDOM can help when it can’t, or they might insist on a prescription when another medication is more appropriate, said Dr. Friedman.

Both he and Dr. Sinclair expect demand for LDOM to continue increasing.

“Word of mouth will drive the next wave of prescriptions,” said Dr. Sinclair. “We are continuing to do work to improve safety, to understand its mechanism of action, and identify ways to improve equity of access to treatment for men and women who are concerned about their hair loss and motivated to treat it,” he said.

Dr. Sinclair and Dr. Friedman report no relevant financial relationships.

SEOUL, SOUTH KOREA – A major challenge for clinical trials in systemic lupus erythematosus (SLE) is how to get the placebo response rate down low enough that the effectiveness of a drug can actually be seen. Better patient selection may be the key.

Speaking at an international congress on SLE, Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, presented on how the heterogeneity of lupus is contributing to the ongoing failure of so many potential therapies in clinical trials.

“It’s a miracle that any drug has been successful in clinical trials,” she told the conference, comparing the few drugs approved for the treatment of lupus with the much larger numbers of approved, targeted biologics that are available for rheumatoid arthritis.

Bianca Nogrady/MDedge News

The problem is that placebo response rates in clinical trials for lupus are high – well over 40% – Dr. Merrill said, and trials aren’t showing a big difference in response rates between the treatment and placebo arms. “If the placebo response is 40%, wouldn’t an effective drug help 80%?” she said. “If it also affects only 40%, does that mean it’s a failed drug?”

Dr. Merrill suggested that better patient selection could be key to achieving lower placebo response rates, which could in turn reveal if and in whom a drug might be effective. “If we could get the placebo response rate down, at least we’d be able to see a little bit better whether the drug is effective, even if it only could work in 50% of the patients,” she said.

Data from research done by the Oklahoma Medical Research Foundation suggested that patients with SLE could be loosely categorized into seven different clusters based on patterns of gene expression in areas such as interferon expression and inflammation pathways.

For example, two of those clusters represented patients with high levels of expression for both interferons and inflammation. “Maybe those are the patients who’d want to be put in a trial for interferon inhibition,” Dr. Merrill said.

This was demonstrated in a trial of type 1 interferon inhibitor anifrolumab (Saphnelo), where patients were sorted into groups according to their level of interferon expression – either high or low – based on expression of certain interferon genes. This revealed that patients in the interferon-high group had a much higher treatment effect than patients in the interferon-low group. But the difference lay in the placebo response.

“The efficacy rate was not that different between the interferon-high and the interferon-low patients,” Dr. Merrill said. “The difference was in the placebo response rate – what they had managed to find was a great marker for sicker patients.”

This phenomenon is not limited to interferon-targeted therapies. Dr. Merrill cited another literature review which looked at subset studies within clinical trials that had delivered disappointing results. This showed consistently that patients who were considered more unwell, by virtue of higher SLE Disease Activity Index (SLEDAI) scores, for example, were more likely to show an effect of treatment.

“You begin to see bigger differences between treatment and placebo because the treatment rate might go up, but mostly because the placebo rate goes down,” she said.

Another issue that could be affecting both placebo and treatment response rates is background medication. “Subset analysis of people on less background drugs was showing lower placebo response rates and better differences between treatments and placebo,” Dr. Merrill said. For example, a recent phase 2 study of anifrolumab took the strategy of actively pursuing tapering of glucocorticoids in patients where that could be done safely. That achieved a lowering of the placebo response rate to the point where a greater difference could be seen between the placebo response and the treatment response rates.

The challenge for clinical trials is therefore to identify which patients to include. “If we could figure out which patients would be the most appropriate [to enroll to fit a particular drug’s mechanism of action], then we could really get ahead of the game,” she said.

The unique problem for lupus clinic trials is the heterogeneity of lupus as a disease, Dr. Merrill said in an interview. “We’re going to have to find combinations of treatments that fit right for each patient, and they won’t necessarily be one size fits all,” she said.

Dr. Merrill said that subset analyses at the phase 2 stage could help identify the patients who responded better to the treatment and could therefore be targeted in phase 3 trials. “Once you take that hypothesis, and if you can establish and validate it in phase 3, now you’ve got yourself a biomarker,” she said.

Richard A. Furie, MD, chief of the division of rheumatology at Northwell Health in New York, agreed that the high placebo response rate was a particular nemesis for researchers involved in lupus clinical trials.

Sara Freeman/MDedge News

Dr. Furie said it could be that selecting sicker patients is a solution to this, as had been suggested in the subset analysis of the anifrolumab studies – which he was involved in – that identified differences in the response rates between interferon-high and interferon-low patients.

But if that was the case, the challenge would be recruiting enough of any particular subset of patients. For example, relatively few patients in the anifrolumab trial were classified as interferon low.

If the interferon expression levels are a marker for patients who are sicker, that could serve as a way to better select patients for clinical trials, he said. But it would also make it harder to achieve recruitment targets.

“I think the major problem in SLE trials is that patients have inflated activity scores, so you can gain SLEDAI scores with a little alopecia and an oral ulcer,” he said. “You can start eliminating those parameters from counting towards entry, but then as soon as you do that, you’re going to have trouble recruiting.”

Dr. Merrill reported consulting for and receiving research support from a range of pharmaceutical companies including Genentech/Roche, GlaxoSmithKline, Pfizer, Janssen, Bristol-Myers Squibb, AbbVie, and anifrolumab manufacturer AstraZeneca. Dr. Furie reported financial relationships with Genentech/Roche, GlaxoSmithKline, Kezar Life Sciences, Kyverna Therapeutics, and Takeda.

SEOUL, SOUTH KOREA – A major challenge for clinical trials in systemic lupus erythematosus (SLE) is how to get the placebo response rate down low enough that the effectiveness of a drug can actually be seen. Better patient selection may be the key.

Speaking at an international congress on SLE, Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, presented on how the heterogeneity of lupus is contributing to the ongoing failure of so many potential therapies in clinical trials.

“It’s a miracle that any drug has been successful in clinical trials,” she told the conference, comparing the few drugs approved for the treatment of lupus with the much larger numbers of approved, targeted biologics that are available for rheumatoid arthritis.

Bianca Nogrady/MDedge News

The problem is that placebo response rates in clinical trials for lupus are high – well over 40% – Dr. Merrill said, and trials aren’t showing a big difference in response rates between the treatment and placebo arms. “If the placebo response is 40%, wouldn’t an effective drug help 80%?” she said. “If it also affects only 40%, does that mean it’s a failed drug?”

Dr. Merrill suggested that better patient selection could be key to achieving lower placebo response rates, which could in turn reveal if and in whom a drug might be effective. “If we could get the placebo response rate down, at least we’d be able to see a little bit better whether the drug is effective, even if it only could work in 50% of the patients,” she said.

Data from research done by the Oklahoma Medical Research Foundation suggested that patients with SLE could be loosely categorized into seven different clusters based on patterns of gene expression in areas such as interferon expression and inflammation pathways.

For example, two of those clusters represented patients with high levels of expression for both interferons and inflammation. “Maybe those are the patients who’d want to be put in a trial for interferon inhibition,” Dr. Merrill said.

This was demonstrated in a trial of type 1 interferon inhibitor anifrolumab (Saphnelo), where patients were sorted into groups according to their level of interferon expression – either high or low – based on expression of certain interferon genes. This revealed that patients in the interferon-high group had a much higher treatment effect than patients in the interferon-low group. But the difference lay in the placebo response.

“The efficacy rate was not that different between the interferon-high and the interferon-low patients,” Dr. Merrill said. “The difference was in the placebo response rate – what they had managed to find was a great marker for sicker patients.”

This phenomenon is not limited to interferon-targeted therapies. Dr. Merrill cited another literature review which looked at subset studies within clinical trials that had delivered disappointing results. This showed consistently that patients who were considered more unwell, by virtue of higher SLE Disease Activity Index (SLEDAI) scores, for example, were more likely to show an effect of treatment.

“You begin to see bigger differences between treatment and placebo because the treatment rate might go up, but mostly because the placebo rate goes down,” she said.

Another issue that could be affecting both placebo and treatment response rates is background medication. “Subset analysis of people on less background drugs was showing lower placebo response rates and better differences between treatments and placebo,” Dr. Merrill said. For example, a recent phase 2 study of anifrolumab took the strategy of actively pursuing tapering of glucocorticoids in patients where that could be done safely. That achieved a lowering of the placebo response rate to the point where a greater difference could be seen between the placebo response and the treatment response rates.

The challenge for clinical trials is therefore to identify which patients to include. “If we could figure out which patients would be the most appropriate [to enroll to fit a particular drug’s mechanism of action], then we could really get ahead of the game,” she said.

The unique problem for lupus clinic trials is the heterogeneity of lupus as a disease, Dr. Merrill said in an interview. “We’re going to have to find combinations of treatments that fit right for each patient, and they won’t necessarily be one size fits all,” she said.

Dr. Merrill said that subset analyses at the phase 2 stage could help identify the patients who responded better to the treatment and could therefore be targeted in phase 3 trials. “Once you take that hypothesis, and if you can establish and validate it in phase 3, now you’ve got yourself a biomarker,” she said.

Richard A. Furie, MD, chief of the division of rheumatology at Northwell Health in New York, agreed that the high placebo response rate was a particular nemesis for researchers involved in lupus clinical trials.

Sara Freeman/MDedge News

Dr. Furie said it could be that selecting sicker patients is a solution to this, as had been suggested in the subset analysis of the anifrolumab studies – which he was involved in – that identified differences in the response rates between interferon-high and interferon-low patients.

But if that was the case, the challenge would be recruiting enough of any particular subset of patients. For example, relatively few patients in the anifrolumab trial were classified as interferon low.

If the interferon expression levels are a marker for patients who are sicker, that could serve as a way to better select patients for clinical trials, he said. But it would also make it harder to achieve recruitment targets.

“I think the major problem in SLE trials is that patients have inflated activity scores, so you can gain SLEDAI scores with a little alopecia and an oral ulcer,” he said. “You can start eliminating those parameters from counting towards entry, but then as soon as you do that, you’re going to have trouble recruiting.”

Dr. Merrill reported consulting for and receiving research support from a range of pharmaceutical companies including Genentech/Roche, GlaxoSmithKline, Pfizer, Janssen, Bristol-Myers Squibb, AbbVie, and anifrolumab manufacturer AstraZeneca. Dr. Furie reported financial relationships with Genentech/Roche, GlaxoSmithKline, Kezar Life Sciences, Kyverna Therapeutics, and Takeda.

SEOUL, SOUTH KOREA – A major challenge for clinical trials in systemic lupus erythematosus (SLE) is how to get the placebo response rate down low enough that the effectiveness of a drug can actually be seen. Better patient selection may be the key.

Speaking at an international congress on SLE, Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, presented on how the heterogeneity of lupus is contributing to the ongoing failure of so many potential therapies in clinical trials.

“It’s a miracle that any drug has been successful in clinical trials,” she told the conference, comparing the few drugs approved for the treatment of lupus with the much larger numbers of approved, targeted biologics that are available for rheumatoid arthritis.

Bianca Nogrady/MDedge News

The problem is that placebo response rates in clinical trials for lupus are high – well over 40% – Dr. Merrill said, and trials aren’t showing a big difference in response rates between the treatment and placebo arms. “If the placebo response is 40%, wouldn’t an effective drug help 80%?” she said. “If it also affects only 40%, does that mean it’s a failed drug?”

Dr. Merrill suggested that better patient selection could be key to achieving lower placebo response rates, which could in turn reveal if and in whom a drug might be effective. “If we could get the placebo response rate down, at least we’d be able to see a little bit better whether the drug is effective, even if it only could work in 50% of the patients,” she said.

Data from research done by the Oklahoma Medical Research Foundation suggested that patients with SLE could be loosely categorized into seven different clusters based on patterns of gene expression in areas such as interferon expression and inflammation pathways.

For example, two of those clusters represented patients with high levels of expression for both interferons and inflammation. “Maybe those are the patients who’d want to be put in a trial for interferon inhibition,” Dr. Merrill said.

This was demonstrated in a trial of type 1 interferon inhibitor anifrolumab (Saphnelo), where patients were sorted into groups according to their level of interferon expression – either high or low – based on expression of certain interferon genes. This revealed that patients in the interferon-high group had a much higher treatment effect than patients in the interferon-low group. But the difference lay in the placebo response.

“The efficacy rate was not that different between the interferon-high and the interferon-low patients,” Dr. Merrill said. “The difference was in the placebo response rate – what they had managed to find was a great marker for sicker patients.”

This phenomenon is not limited to interferon-targeted therapies. Dr. Merrill cited another literature review which looked at subset studies within clinical trials that had delivered disappointing results. This showed consistently that patients who were considered more unwell, by virtue of higher SLE Disease Activity Index (SLEDAI) scores, for example, were more likely to show an effect of treatment.

“You begin to see bigger differences between treatment and placebo because the treatment rate might go up, but mostly because the placebo rate goes down,” she said.

Another issue that could be affecting both placebo and treatment response rates is background medication. “Subset analysis of people on less background drugs was showing lower placebo response rates and better differences between treatments and placebo,” Dr. Merrill said. For example, a recent phase 2 study of anifrolumab took the strategy of actively pursuing tapering of glucocorticoids in patients where that could be done safely. That achieved a lowering of the placebo response rate to the point where a greater difference could be seen between the placebo response and the treatment response rates.

The challenge for clinical trials is therefore to identify which patients to include. “If we could figure out which patients would be the most appropriate [to enroll to fit a particular drug’s mechanism of action], then we could really get ahead of the game,” she said.

The unique problem for lupus clinic trials is the heterogeneity of lupus as a disease, Dr. Merrill said in an interview. “We’re going to have to find combinations of treatments that fit right for each patient, and they won’t necessarily be one size fits all,” she said.

Dr. Merrill said that subset analyses at the phase 2 stage could help identify the patients who responded better to the treatment and could therefore be targeted in phase 3 trials. “Once you take that hypothesis, and if you can establish and validate it in phase 3, now you’ve got yourself a biomarker,” she said.

Richard A. Furie, MD, chief of the division of rheumatology at Northwell Health in New York, agreed that the high placebo response rate was a particular nemesis for researchers involved in lupus clinical trials.

Sara Freeman/MDedge News

Dr. Furie said it could be that selecting sicker patients is a solution to this, as had been suggested in the subset analysis of the anifrolumab studies – which he was involved in – that identified differences in the response rates between interferon-high and interferon-low patients.

But if that was the case, the challenge would be recruiting enough of any particular subset of patients. For example, relatively few patients in the anifrolumab trial were classified as interferon low.

If the interferon expression levels are a marker for patients who are sicker, that could serve as a way to better select patients for clinical trials, he said. But it would also make it harder to achieve recruitment targets.

“I think the major problem in SLE trials is that patients have inflated activity scores, so you can gain SLEDAI scores with a little alopecia and an oral ulcer,” he said. “You can start eliminating those parameters from counting towards entry, but then as soon as you do that, you’re going to have trouble recruiting.”

Dr. Merrill reported consulting for and receiving research support from a range of pharmaceutical companies including Genentech/Roche, GlaxoSmithKline, Pfizer, Janssen, Bristol-Myers Squibb, AbbVie, and anifrolumab manufacturer AstraZeneca. Dr. Furie reported financial relationships with Genentech/Roche, GlaxoSmithKline, Kezar Life Sciences, Kyverna Therapeutics, and Takeda.

A topical gel that may work faster than erectile dysfunction pills has been approved for over-the-counter use in the United States. The gel, which can help users get an erection within 10 minutes, is already available without a prescription in Europe.

The Food and Drug Administration has approved the drug, called Eroxon, noting that it is a first-of-its-kind treatment. Eroxon is made by the British pharmaceutical company Futura Medical, which specializes in drugs that are given through the skin.

According to the product’s leaflet, Eroxon “stimulates blood flow in the penis through a unique physical cooling then warming effect, helping you get and keep an erection hard enough for sex.” The company said on the product’s website that 65% of people who used the drug were able to have sex. 

A company spokesperson told CNN that the price of the product has not been set in the United States, but it costs the equivalent of about $31 in the United Kingdom. Futura Medical has not announced when it will be available in the United States.

Harvard Health reports that 30 million people in the United States have erectile dysfunction, which means a person cannot get an erection at all or one firm enough to have sex. The disorder is often linked to other physical or mental health problems, such as heart problems or clogged arteries.

Erectile dysfunction affects 1% of men in their 40s, 17% of men in their 60s, and nearly 50% of men who are age 75 or older, according to Harvard Health.

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

A topical gel that may work faster than erectile dysfunction pills has been approved for over-the-counter use in the United States. The gel, which can help users get an erection within 10 minutes, is already available without a prescription in Europe.

The Food and Drug Administration has approved the drug, called Eroxon, noting that it is a first-of-its-kind treatment. Eroxon is made by the British pharmaceutical company Futura Medical, which specializes in drugs that are given through the skin.

According to the product’s leaflet, Eroxon “stimulates blood flow in the penis through a unique physical cooling then warming effect, helping you get and keep an erection hard enough for sex.” The company said on the product’s website that 65% of people who used the drug were able to have sex. 

A company spokesperson told CNN that the price of the product has not been set in the United States, but it costs the equivalent of about $31 in the United Kingdom. Futura Medical has not announced when it will be available in the United States.

Harvard Health reports that 30 million people in the United States have erectile dysfunction, which means a person cannot get an erection at all or one firm enough to have sex. The disorder is often linked to other physical or mental health problems, such as heart problems or clogged arteries.

Erectile dysfunction affects 1% of men in their 40s, 17% of men in their 60s, and nearly 50% of men who are age 75 or older, according to Harvard Health.

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

A topical gel that may work faster than erectile dysfunction pills has been approved for over-the-counter use in the United States. The gel, which can help users get an erection within 10 minutes, is already available without a prescription in Europe.

The Food and Drug Administration has approved the drug, called Eroxon, noting that it is a first-of-its-kind treatment. Eroxon is made by the British pharmaceutical company Futura Medical, which specializes in drugs that are given through the skin.

According to the product’s leaflet, Eroxon “stimulates blood flow in the penis through a unique physical cooling then warming effect, helping you get and keep an erection hard enough for sex.” The company said on the product’s website that 65% of people who used the drug were able to have sex. 

A company spokesperson told CNN that the price of the product has not been set in the United States, but it costs the equivalent of about $31 in the United Kingdom. Futura Medical has not announced when it will be available in the United States.

Harvard Health reports that 30 million people in the United States have erectile dysfunction, which means a person cannot get an erection at all or one firm enough to have sex. The disorder is often linked to other physical or mental health problems, such as heart problems or clogged arteries.

Erectile dysfunction affects 1% of men in their 40s, 17% of men in their 60s, and nearly 50% of men who are age 75 or older, according to Harvard Health.

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

Infections were the most common adverse events associated with the use of microwave energy devices for hyperhidrosis over a 9-year period, an analysis of reports submitted to the FDA Manufacturer and User Facility Device Experience (MAUDE) database showed.

While microwave energy devices (MEDs) are used to treat hyperhidrosis, the largest MED clinical trial included only 101 patients, Samantha Jo Albucker and Shari Lipner, MD, PhD, wrote in a research letter reporting the results.

For the study, published online in the Journal of the American Academy of Dermatology, Ms. Albucker, a student at Tulane University, New Orleans, and Dr. Lipner, associate professor of clinical dermatology at Weill Cornell Medicine, New York, searched the MAUDE database between Feb. 28, 2013, and Dec. 29, 2022, for adverse events (AEs) involving MEDs for hyperhidrosis treatment. Of the 502 medical device reports identified over the study period, the axilla was the most frequent injury site in 50.4% of cases. The three most common complications were infections (45.4%); neurological symptoms including neuropathy, nerve damage, and numbness (21.7%); and burns/ulcerations/erosions (19.1%).

In other findings, 2.4% of patients required hospitalization, most often because of infection (83.3%), followed by burn and coma (8.3% each). The average symptom onset was 2 months postprocedure, and the most common treatment was antibiotics in 62.2% of cases, followed by incision and drainage/aspiration in 21.7% of cases.

A codiagnosis of hidradenitis suppurativa (HS) was reported in 5.4% of all medical device reports. The researchers noted that in a published randomized clinical trial of eight HS patients undergoing MED treatment to assess the effect on HS symptoms, the treatment showed no clinical advantage. In addition, they referred to two case reports describing new-onset HS after MED treatment for hyperhidrosis.

“Therefore, we recommend questioning patients about HS history and examining for HS clinical findings before performing MED for hyperhidrosis,” they wrote, adding that the data, “taken together, suggests that avoidance of MED treatment of hyperhidrosis in HS patients is prudent and alternative treatments may be prescribed.”

The researchers acknowledged certain limitations of their analysis, including uncompleted medical device reports, patient reporting, and unverified causes of adverse events. “Large multicenter studies are needed to corroborate our results,” they concluded.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, said that primary idiopathic hyperhidrosis is a common medical condition that is often overlooked as a legitimate concern, and causes a quality-of-life burden. “Even with the striking numbers in the millions, there are limited treatment options available for axillary let alone other forms of primary hyperhidrosis,” said Dr. Friedman, who was not involved with the study.

“Therefore, for the short treatment list we have, it is important to have some predictive power with respect to clinical impact to provide realistic expectations as well as potential adverse events to ensure best practices and meaningful patient guidance. In this research letter, our colleagues highlight complications that can ensue from microwave therapy for hyperhidrosis and the frequency of said adverse events. Knowing these data is half the battle, and I for one would not have assumed infection was number one on the list of adverse events.”

Ms. Albucker had no relevant conflicts of interest to disclose. Dr. Lipner disclosed that she has served as a consultant for Ortho Dermatologics, Hoth Therapeutics, BelleTorus Corporation, and Moberg Pharmaceuticals.

Dr. Friedman disclosed that he is a consultant and/or advisory board member for Medscape/SanovaWorks, Oakstone Institute, L’Oréal, La Roche Posay, Galderma, Aveeno, Ortho Dermatologic, Microcures, Pfizer, Novartis, Lilly, Hoth Therapeutics, Zylo Therapeutics, BMS, Vial, Janssen, Novocure, Dermavant, Regeneron/Sanofi, and Incyte. He has also received grants from Pfizer, the Dermatology Foundation, Lilly, Janssen, Incyte, and Galderma.

Infections were the most common adverse events associated with the use of microwave energy devices for hyperhidrosis over a 9-year period, an analysis of reports submitted to the FDA Manufacturer and User Facility Device Experience (MAUDE) database showed.

While microwave energy devices (MEDs) are used to treat hyperhidrosis, the largest MED clinical trial included only 101 patients, Samantha Jo Albucker and Shari Lipner, MD, PhD, wrote in a research letter reporting the results.

For the study, published online in the Journal of the American Academy of Dermatology, Ms. Albucker, a student at Tulane University, New Orleans, and Dr. Lipner, associate professor of clinical dermatology at Weill Cornell Medicine, New York, searched the MAUDE database between Feb. 28, 2013, and Dec. 29, 2022, for adverse events (AEs) involving MEDs for hyperhidrosis treatment. Of the 502 medical device reports identified over the study period, the axilla was the most frequent injury site in 50.4% of cases. The three most common complications were infections (45.4%); neurological symptoms including neuropathy, nerve damage, and numbness (21.7%); and burns/ulcerations/erosions (19.1%).

In other findings, 2.4% of patients required hospitalization, most often because of infection (83.3%), followed by burn and coma (8.3% each). The average symptom onset was 2 months postprocedure, and the most common treatment was antibiotics in 62.2% of cases, followed by incision and drainage/aspiration in 21.7% of cases.

A codiagnosis of hidradenitis suppurativa (HS) was reported in 5.4% of all medical device reports. The researchers noted that in a published randomized clinical trial of eight HS patients undergoing MED treatment to assess the effect on HS symptoms, the treatment showed no clinical advantage. In addition, they referred to two case reports describing new-onset HS after MED treatment for hyperhidrosis.

“Therefore, we recommend questioning patients about HS history and examining for HS clinical findings before performing MED for hyperhidrosis,” they wrote, adding that the data, “taken together, suggests that avoidance of MED treatment of hyperhidrosis in HS patients is prudent and alternative treatments may be prescribed.”

The researchers acknowledged certain limitations of their analysis, including uncompleted medical device reports, patient reporting, and unverified causes of adverse events. “Large multicenter studies are needed to corroborate our results,” they concluded.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, said that primary idiopathic hyperhidrosis is a common medical condition that is often overlooked as a legitimate concern, and causes a quality-of-life burden. “Even with the striking numbers in the millions, there are limited treatment options available for axillary let alone other forms of primary hyperhidrosis,” said Dr. Friedman, who was not involved with the study.

“Therefore, for the short treatment list we have, it is important to have some predictive power with respect to clinical impact to provide realistic expectations as well as potential adverse events to ensure best practices and meaningful patient guidance. In this research letter, our colleagues highlight complications that can ensue from microwave therapy for hyperhidrosis and the frequency of said adverse events. Knowing these data is half the battle, and I for one would not have assumed infection was number one on the list of adverse events.”

Ms. Albucker had no relevant conflicts of interest to disclose. Dr. Lipner disclosed that she has served as a consultant for Ortho Dermatologics, Hoth Therapeutics, BelleTorus Corporation, and Moberg Pharmaceuticals.

Dr. Friedman disclosed that he is a consultant and/or advisory board member for Medscape/SanovaWorks, Oakstone Institute, L’Oréal, La Roche Posay, Galderma, Aveeno, Ortho Dermatologic, Microcures, Pfizer, Novartis, Lilly, Hoth Therapeutics, Zylo Therapeutics, BMS, Vial, Janssen, Novocure, Dermavant, Regeneron/Sanofi, and Incyte. He has also received grants from Pfizer, the Dermatology Foundation, Lilly, Janssen, Incyte, and Galderma.

Infections were the most common adverse events associated with the use of microwave energy devices for hyperhidrosis over a 9-year period, an analysis of reports submitted to the FDA Manufacturer and User Facility Device Experience (MAUDE) database showed.

While microwave energy devices (MEDs) are used to treat hyperhidrosis, the largest MED clinical trial included only 101 patients, Samantha Jo Albucker and Shari Lipner, MD, PhD, wrote in a research letter reporting the results.

For the study, published online in the Journal of the American Academy of Dermatology, Ms. Albucker, a student at Tulane University, New Orleans, and Dr. Lipner, associate professor of clinical dermatology at Weill Cornell Medicine, New York, searched the MAUDE database between Feb. 28, 2013, and Dec. 29, 2022, for adverse events (AEs) involving MEDs for hyperhidrosis treatment. Of the 502 medical device reports identified over the study period, the axilla was the most frequent injury site in 50.4% of cases. The three most common complications were infections (45.4%); neurological symptoms including neuropathy, nerve damage, and numbness (21.7%); and burns/ulcerations/erosions (19.1%).

In other findings, 2.4% of patients required hospitalization, most often because of infection (83.3%), followed by burn and coma (8.3% each). The average symptom onset was 2 months postprocedure, and the most common treatment was antibiotics in 62.2% of cases, followed by incision and drainage/aspiration in 21.7% of cases.

A codiagnosis of hidradenitis suppurativa (HS) was reported in 5.4% of all medical device reports. The researchers noted that in a published randomized clinical trial of eight HS patients undergoing MED treatment to assess the effect on HS symptoms, the treatment showed no clinical advantage. In addition, they referred to two case reports describing new-onset HS after MED treatment for hyperhidrosis.

“Therefore, we recommend questioning patients about HS history and examining for HS clinical findings before performing MED for hyperhidrosis,” they wrote, adding that the data, “taken together, suggests that avoidance of MED treatment of hyperhidrosis in HS patients is prudent and alternative treatments may be prescribed.”

The researchers acknowledged certain limitations of their analysis, including uncompleted medical device reports, patient reporting, and unverified causes of adverse events. “Large multicenter studies are needed to corroborate our results,” they concluded.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, said that primary idiopathic hyperhidrosis is a common medical condition that is often overlooked as a legitimate concern, and causes a quality-of-life burden. “Even with the striking numbers in the millions, there are limited treatment options available for axillary let alone other forms of primary hyperhidrosis,” said Dr. Friedman, who was not involved with the study.

“Therefore, for the short treatment list we have, it is important to have some predictive power with respect to clinical impact to provide realistic expectations as well as potential adverse events to ensure best practices and meaningful patient guidance. In this research letter, our colleagues highlight complications that can ensue from microwave therapy for hyperhidrosis and the frequency of said adverse events. Knowing these data is half the battle, and I for one would not have assumed infection was number one on the list of adverse events.”

Ms. Albucker had no relevant conflicts of interest to disclose. Dr. Lipner disclosed that she has served as a consultant for Ortho Dermatologics, Hoth Therapeutics, BelleTorus Corporation, and Moberg Pharmaceuticals.

Dr. Friedman disclosed that he is a consultant and/or advisory board member for Medscape/SanovaWorks, Oakstone Institute, L’Oréal, La Roche Posay, Galderma, Aveeno, Ortho Dermatologic, Microcures, Pfizer, Novartis, Lilly, Hoth Therapeutics, Zylo Therapeutics, BMS, Vial, Janssen, Novocure, Dermavant, Regeneron/Sanofi, and Incyte. He has also received grants from Pfizer, the Dermatology Foundation, Lilly, Janssen, Incyte, and Galderma.

Medscape’s Editor-in-Chief Eric Topol, MD, referred to continual noninvasive, cuffless, accurate blood pressure devices as “a holy grail in sensor technology.”

He personally tested a cuff-calibrated, over-the-counter device available in Europe that claims to monitor daily blood pressure changes and produce data that can help physicians titrate medications.

Dr. Topol does not believe that it is ready for prime time. Yes, cuffless devices are easy to use, and generate lots of data. But are those data accurate?

Many experts say not yet, even as the market continues to grow and more devices are introduced and highlighted at high-profile consumer events.
 

Burned before

Limitations of cuffed devices are well known, including errors related to cuff size, patient positioning, patient habits or behaviors (for example, caffeine/nicotine use, acute meal digestion, full bladder, very recent physical activity) and clinicians’ failure to take accurate measurements.

But are the currently available cuffless devices acceptable substitutes?

Like many clinicians, Timothy B. Plante, MD, MHS, assistant professor at the University of Vermont Medical Center thrombosis & hemostasis program in Burlington, is very excited about cuffless technology. However, “we’ve been burned by it before,” he said in an interview.

Dr. Plante’s 2016 validation study of an instant blood pressure smartphone app found that its measurements were “highly inaccurate,” with such low sensitivity that more than three-quarters of individuals with hypertensive blood levels would be falsely reassured that their blood pressure was in the normal range.

His team’s 2023 review of the current landscape, which includes more sophisticated devices, concluded that accuracy remains an issue: “Unfortunately, the pace of regulation of these devices has failed to match the speed of innovation and direct availability to patient consumers. There is an urgent need to develop a consensus on standards by which cuffless BP devices can be tested for accuracy.”
 

Devices, indications differ

Cuffless devices estimate blood pressure indirectly. Most operate based on pulse wave analysis and pulse arrival time (PWA-PAT), explained Ramakrishna Mukkamala, PhD, in a commentary. Dr. Mukkamala is a professor in the departments of bioengineering and anesthesiology and perioperative medicine at the University of Pittsburgh.

PWA involves measuring a peripheral arterial waveform using an optical sensor such as the green lights on the back of a wrist-worn device, or a ‘force sensor’ such as a finger cuff or pressing on a smartphone. Certain features are extracted from the waveform using machine learning and calibrated to blood pressure values.

PAT techniques work together with PWA; they record the ECG and extract features from that signal as well as the arterial waveform for calibration to blood pressure values.

The algorithm used to generate the BP numbers comprises a proprietary baseline model that may include demographics and other patient characteristics. A cuff measurement is often part of the baseline model because most cuffless devices require periodic (typically weekly or monthly) calibration using a cuffed device.

Cuffless devices that require cuff calibration compare the estimate they get to the cuff-calibrated number. In this scenario, the cuffless device may come up with the same blood pressure numbers simply because the baseline model – which is made up of thousands of data points relevant to the patient – has not changed.

This has led some experts to question whether PWA-PAT cuffless device readings actually add anything to the baseline model.

They don’t, according to Microsoft Research in what Dr. Mukkamala and coauthors referred to (in a review published in Hypertension) as “a complex article describing perhaps the most important and highest resource project to date (Aurora Project) on assessing the accuracy of PWA and PWA devices.”

The Microsoft article was written for bioengineers. The review in Hypertension explains the project for clinicians, and concludes that, “Cuffless BP devices based on PWA and PWA-PAT, which are similar to some regulatory-cleared devices, were of no additional value in measuring auscultatory or 24-hour ambulatory cuff BP when compared with a baseline model in which BP was predicted without an actual measurement.”
 

IEEE and FDA validation

Despite these concerns, several cuffless devices using PWA and PAT have been cleared by the Food and Drug Administration.

Validating cuffless devices is no simple matter. The Institute of Electrical and Electronics Engineers published a validation protocol for cuffless blood pressure devices in 2014 that was amended in 2019 to include a requirement to evaluate performance in different positions and in the presence of motion with varying degrees of noise artifact.

However, Daichi Shimbo, MD, codirector of the Columbia Hypertension Center in New York and vice chair of the American Heart Association Statement on blood pressure monitoring, and colleagues point out limitations, even in the updated standard. These include not requiring evaluation for drift over time; lack of specific dynamic testing protocols for stressors such as exercise or environmental temperatures; and an unsuitable reference standard (oscillometric cuff-based devices) during movement.

Dr. Shimbo said in an interview that, although he is excited about them, “these cuffless devices are not aligned with regulatory bodies. If a device gives someone a wrong blood pressure, they might be diagnosed with hypertension when they don’t have it or might miss the fact that they’re hypertensive because they get a normal blood pressure reading. If there’s no yardstick by which you say these devices are good, what are we really doing – helping, or causing a problem?”

“The specifics of how a device estimates blood pressure can determine what testing is needed to ensure that it is providing accurate performance in the intended conditions of use,” Jeremy Kahn, an FDA press officer, said in an interview. “For example, for cuffless devices that are calibrated initially with a cuff-based blood pressure device, the cuffless device needs to specify the period over which it can provide accurate readings and have testing to demonstrate that it provides accurate results over that period of use.”

The FDA said its testing is different from what the Microsoft Aurora Project used in their study.

“The intent of that testing, as the agency understands it, is to evaluate whether the device is providing useful input based on the current physiology of the patient rather than relying on predetermined values based on calibration or patient attributes. We evaluate this clinically in two separate tests: an induced change in blood pressure test and tracking of natural blood pressure changes with longer term device use,” Mr. Kahn explained.

Analyzing a device’s performance on individuals who have had natural changes in blood pressure as compared to a calibration value or initial reading “can also help discern if the device is using physiological data from the patient to determine their blood pressure accurately,” he said.

Experts interviewed for this article who remain skeptical about cuffless BP monitoring question whether the numbers that appear during the induced blood pressure change, and with the natural blood pressure changes that may occur over time, accurately reflect a patient’s blood pressure.

“The FDA doesn’t approve these devices; they clear them,” Dr. Shimbo pointed out. “Clearing them means they can be sold to the general public in the U.S. It’s not a strong statement that they’re accurate.”
 

Moving toward validation, standards

Ultimately, cuffless BP monitors may require more than one validation protocol and standard, depending on their technology, how and where they will be used, and by whom.

And as Dr. Plante and colleagues write, “Importantly, validation should be performed in diverse and special populations, including pregnant women and individuals across a range of heart rates, skin tones, wrist sizes, common arrhythmias, and beta-blocker use.”

Organizations that might be expected to help move validation and standards forward have mostly remained silent. The American Medical Association’s US Blood Pressure Validated Device Listing website includes only cuffed devices, as does the website of the international scientific nonprofit STRIDE BP.

The European Society of Hypertension 2022 consensus statement on cuffless devices concluded that, until there is an internationally accepted accuracy standard and the devices have been tested in healthy people and those with suspected or diagnosed hypertension, “cuffless BP devices should not be used for the evaluation or management of hypertension in clinical practice.”

This month, ESH published recommendations for “specific, clinically meaningful, and pragmatic validation procedures for different types of intermittent cuffless devices” that will be presented at their upcoming annual meeting June 26.

Updated protocols from IEEE “are coming out soon,” according to Dr. Shimbo. The FDA says currently cleared devices won’t need to revalidate according to new standards unless the sponsor makes significant modifications in software algorithms, device hardware, or targeted patient populations.
 

Device makers take the initiative

In the face of conflicting reports on accuracy and lack of a robust standard, some device makers are publishing their own tests or encouraging validation by potential customers.

For example, institutions that are considering using the Biobeat cuffless blood pressure monitor watch “usually start with small pilots with our devices to do internal validation,” Lior Ben Shettrit, the company’s vice president of business development, said in an interview. “Only after they complete the internal validation are they willing to move forward to full implementation.”

Cardiologist Dean Nachman, MD, is leading validation studies of the Biobeat device at the Hadassah Ein Kerem Medical Center in Jerusalem. For the first validation, the team recruited 1,057 volunteers who did a single blood pressure measurement with the cuffless device and with a cuffed device.

“We found 96.3% agreement in identifying hypertension and an interclass correlation coefficient of 0.99 and 0.97 for systolic and diastolic measurements, respectively,” he said. “Then we took it to the next level and compared the device to ambulatory 24-hour blood pressure monitoring and found comparable measurements.”

The investigators are not done yet. “We need data from thousands of patients, with subgroups, to not have any concerns,” he says. “Right now, we are using the device as a general monitor – as an EKG plus heart rate plus oxygen saturation level monitor – and as a blood pressure monitor for 24-hour blood pressure monitoring.”

The developers of the Aktiia device, which is the one Dr. Topol tested, take a different perspective. “When somebody introduces a new technology that is disrupting something that has been in place for over 100 years, there will always be some grumblings, ruffling of feathers, people saying it’s not ready, it’s not ready, it’s not ready,” Aktiia’s chief medical officer Jay Shah, MD, noted.

“But a lot of those comments are coming from the isolation of an ivory tower,” he said.

Aktiia cofounder and chief technology officer Josep Solà said that “no device is probably as accurate as if you have an invasive catheter,” adding that “we engage patients to look at their blood pressure day by day. … If each individual measurement of each of those patient is slightly less accurate than a cuff, who cares? We have 40 measurements per day on each patient. The accuracy and precision of each of those is good.”

Researchers from the George Institute for Global Health recently compared the Aktiia device to conventional ambulatory monitoring in 41 patients and found that “it did not accurately track night-time BP decline and results suggested it was unable to track medication-induced BP changes.”

“In the context of 24/7 monitoring of hypertensive patients,” Mr. Solà said, “whatever you do, if it’s better than a sham device or a baseline model and you track the blood pressure changes, it’s a hundred times much better than doing nothing.”

Dr. Nachman and Dr. Plante reported no relevant financial relationships. Dr. Shimbo reported that he received funding from NIH and has consulted for Abbott Vascular, Edward Lifesciences, Medtronic, and Tryton Medical.

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

Medscape’s Editor-in-Chief Eric Topol, MD, referred to continual noninvasive, cuffless, accurate blood pressure devices as “a holy grail in sensor technology.”

He personally tested a cuff-calibrated, over-the-counter device available in Europe that claims to monitor daily blood pressure changes and produce data that can help physicians titrate medications.

Dr. Topol does not believe that it is ready for prime time. Yes, cuffless devices are easy to use, and generate lots of data. But are those data accurate?

Many experts say not yet, even as the market continues to grow and more devices are introduced and highlighted at high-profile consumer events.
 

Burned before

Limitations of cuffed devices are well known, including errors related to cuff size, patient positioning, patient habits or behaviors (for example, caffeine/nicotine use, acute meal digestion, full bladder, very recent physical activity) and clinicians’ failure to take accurate measurements.

But are the currently available cuffless devices acceptable substitutes?

Like many clinicians, Timothy B. Plante, MD, MHS, assistant professor at the University of Vermont Medical Center thrombosis & hemostasis program in Burlington, is very excited about cuffless technology. However, “we’ve been burned by it before,” he said in an interview.

Dr. Plante’s 2016 validation study of an instant blood pressure smartphone app found that its measurements were “highly inaccurate,” with such low sensitivity that more than three-quarters of individuals with hypertensive blood levels would be falsely reassured that their blood pressure was in the normal range.

His team’s 2023 review of the current landscape, which includes more sophisticated devices, concluded that accuracy remains an issue: “Unfortunately, the pace of regulation of these devices has failed to match the speed of innovation and direct availability to patient consumers. There is an urgent need to develop a consensus on standards by which cuffless BP devices can be tested for accuracy.”
 

Devices, indications differ

Cuffless devices estimate blood pressure indirectly. Most operate based on pulse wave analysis and pulse arrival time (PWA-PAT), explained Ramakrishna Mukkamala, PhD, in a commentary. Dr. Mukkamala is a professor in the departments of bioengineering and anesthesiology and perioperative medicine at the University of Pittsburgh.

PWA involves measuring a peripheral arterial waveform using an optical sensor such as the green lights on the back of a wrist-worn device, or a ‘force sensor’ such as a finger cuff or pressing on a smartphone. Certain features are extracted from the waveform using machine learning and calibrated to blood pressure values.

PAT techniques work together with PWA; they record the ECG and extract features from that signal as well as the arterial waveform for calibration to blood pressure values.

The algorithm used to generate the BP numbers comprises a proprietary baseline model that may include demographics and other patient characteristics. A cuff measurement is often part of the baseline model because most cuffless devices require periodic (typically weekly or monthly) calibration using a cuffed device.

Cuffless devices that require cuff calibration compare the estimate they get to the cuff-calibrated number. In this scenario, the cuffless device may come up with the same blood pressure numbers simply because the baseline model – which is made up of thousands of data points relevant to the patient – has not changed.

This has led some experts to question whether PWA-PAT cuffless device readings actually add anything to the baseline model.

They don’t, according to Microsoft Research in what Dr. Mukkamala and coauthors referred to (in a review published in Hypertension) as “a complex article describing perhaps the most important and highest resource project to date (Aurora Project) on assessing the accuracy of PWA and PWA devices.”

The Microsoft article was written for bioengineers. The review in Hypertension explains the project for clinicians, and concludes that, “Cuffless BP devices based on PWA and PWA-PAT, which are similar to some regulatory-cleared devices, were of no additional value in measuring auscultatory or 24-hour ambulatory cuff BP when compared with a baseline model in which BP was predicted without an actual measurement.”
 

IEEE and FDA validation

Despite these concerns, several cuffless devices using PWA and PAT have been cleared by the Food and Drug Administration.

Validating cuffless devices is no simple matter. The Institute of Electrical and Electronics Engineers published a validation protocol for cuffless blood pressure devices in 2014 that was amended in 2019 to include a requirement to evaluate performance in different positions and in the presence of motion with varying degrees of noise artifact.

However, Daichi Shimbo, MD, codirector of the Columbia Hypertension Center in New York and vice chair of the American Heart Association Statement on blood pressure monitoring, and colleagues point out limitations, even in the updated standard. These include not requiring evaluation for drift over time; lack of specific dynamic testing protocols for stressors such as exercise or environmental temperatures; and an unsuitable reference standard (oscillometric cuff-based devices) during movement.

Dr. Shimbo said in an interview that, although he is excited about them, “these cuffless devices are not aligned with regulatory bodies. If a device gives someone a wrong blood pressure, they might be diagnosed with hypertension when they don’t have it or might miss the fact that they’re hypertensive because they get a normal blood pressure reading. If there’s no yardstick by which you say these devices are good, what are we really doing – helping, or causing a problem?”

“The specifics of how a device estimates blood pressure can determine what testing is needed to ensure that it is providing accurate performance in the intended conditions of use,” Jeremy Kahn, an FDA press officer, said in an interview. “For example, for cuffless devices that are calibrated initially with a cuff-based blood pressure device, the cuffless device needs to specify the period over which it can provide accurate readings and have testing to demonstrate that it provides accurate results over that period of use.”

The FDA said its testing is different from what the Microsoft Aurora Project used in their study.

“The intent of that testing, as the agency understands it, is to evaluate whether the device is providing useful input based on the current physiology of the patient rather than relying on predetermined values based on calibration or patient attributes. We evaluate this clinically in two separate tests: an induced change in blood pressure test and tracking of natural blood pressure changes with longer term device use,” Mr. Kahn explained.

Analyzing a device’s performance on individuals who have had natural changes in blood pressure as compared to a calibration value or initial reading “can also help discern if the device is using physiological data from the patient to determine their blood pressure accurately,” he said.

Experts interviewed for this article who remain skeptical about cuffless BP monitoring question whether the numbers that appear during the induced blood pressure change, and with the natural blood pressure changes that may occur over time, accurately reflect a patient’s blood pressure.

“The FDA doesn’t approve these devices; they clear them,” Dr. Shimbo pointed out. “Clearing them means they can be sold to the general public in the U.S. It’s not a strong statement that they’re accurate.”
 

Moving toward validation, standards

Ultimately, cuffless BP monitors may require more than one validation protocol and standard, depending on their technology, how and where they will be used, and by whom.

And as Dr. Plante and colleagues write, “Importantly, validation should be performed in diverse and special populations, including pregnant women and individuals across a range of heart rates, skin tones, wrist sizes, common arrhythmias, and beta-blocker use.”

Organizations that might be expected to help move validation and standards forward have mostly remained silent. The American Medical Association’s US Blood Pressure Validated Device Listing website includes only cuffed devices, as does the website of the international scientific nonprofit STRIDE BP.

The European Society of Hypertension 2022 consensus statement on cuffless devices concluded that, until there is an internationally accepted accuracy standard and the devices have been tested in healthy people and those with suspected or diagnosed hypertension, “cuffless BP devices should not be used for the evaluation or management of hypertension in clinical practice.”

This month, ESH published recommendations for “specific, clinically meaningful, and pragmatic validation procedures for different types of intermittent cuffless devices” that will be presented at their upcoming annual meeting June 26.

Updated protocols from IEEE “are coming out soon,” according to Dr. Shimbo. The FDA says currently cleared devices won’t need to revalidate according to new standards unless the sponsor makes significant modifications in software algorithms, device hardware, or targeted patient populations.
 

Device makers take the initiative

In the face of conflicting reports on accuracy and lack of a robust standard, some device makers are publishing their own tests or encouraging validation by potential customers.

For example, institutions that are considering using the Biobeat cuffless blood pressure monitor watch “usually start with small pilots with our devices to do internal validation,” Lior Ben Shettrit, the company’s vice president of business development, said in an interview. “Only after they complete the internal validation are they willing to move forward to full implementation.”

Cardiologist Dean Nachman, MD, is leading validation studies of the Biobeat device at the Hadassah Ein Kerem Medical Center in Jerusalem. For the first validation, the team recruited 1,057 volunteers who did a single blood pressure measurement with the cuffless device and with a cuffed device.

“We found 96.3% agreement in identifying hypertension and an interclass correlation coefficient of 0.99 and 0.97 for systolic and diastolic measurements, respectively,” he said. “Then we took it to the next level and compared the device to ambulatory 24-hour blood pressure monitoring and found comparable measurements.”

The investigators are not done yet. “We need data from thousands of patients, with subgroups, to not have any concerns,” he says. “Right now, we are using the device as a general monitor – as an EKG plus heart rate plus oxygen saturation level monitor – and as a blood pressure monitor for 24-hour blood pressure monitoring.”

The developers of the Aktiia device, which is the one Dr. Topol tested, take a different perspective. “When somebody introduces a new technology that is disrupting something that has been in place for over 100 years, there will always be some grumblings, ruffling of feathers, people saying it’s not ready, it’s not ready, it’s not ready,” Aktiia’s chief medical officer Jay Shah, MD, noted.

“But a lot of those comments are coming from the isolation of an ivory tower,” he said.

Aktiia cofounder and chief technology officer Josep Solà said that “no device is probably as accurate as if you have an invasive catheter,” adding that “we engage patients to look at their blood pressure day by day. … If each individual measurement of each of those patient is slightly less accurate than a cuff, who cares? We have 40 measurements per day on each patient. The accuracy and precision of each of those is good.”

Researchers from the George Institute for Global Health recently compared the Aktiia device to conventional ambulatory monitoring in 41 patients and found that “it did not accurately track night-time BP decline and results suggested it was unable to track medication-induced BP changes.”

“In the context of 24/7 monitoring of hypertensive patients,” Mr. Solà said, “whatever you do, if it’s better than a sham device or a baseline model and you track the blood pressure changes, it’s a hundred times much better than doing nothing.”

Dr. Nachman and Dr. Plante reported no relevant financial relationships. Dr. Shimbo reported that he received funding from NIH and has consulted for Abbott Vascular, Edward Lifesciences, Medtronic, and Tryton Medical.

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

Medscape’s Editor-in-Chief Eric Topol, MD, referred to continual noninvasive, cuffless, accurate blood pressure devices as “a holy grail in sensor technology.”

He personally tested a cuff-calibrated, over-the-counter device available in Europe that claims to monitor daily blood pressure changes and produce data that can help physicians titrate medications.

Dr. Topol does not believe that it is ready for prime time. Yes, cuffless devices are easy to use, and generate lots of data. But are those data accurate?

Many experts say not yet, even as the market continues to grow and more devices are introduced and highlighted at high-profile consumer events.
 

Burned before

Limitations of cuffed devices are well known, including errors related to cuff size, patient positioning, patient habits or behaviors (for example, caffeine/nicotine use, acute meal digestion, full bladder, very recent physical activity) and clinicians’ failure to take accurate measurements.

But are the currently available cuffless devices acceptable substitutes?

Like many clinicians, Timothy B. Plante, MD, MHS, assistant professor at the University of Vermont Medical Center thrombosis & hemostasis program in Burlington, is very excited about cuffless technology. However, “we’ve been burned by it before,” he said in an interview.

Dr. Plante’s 2016 validation study of an instant blood pressure smartphone app found that its measurements were “highly inaccurate,” with such low sensitivity that more than three-quarters of individuals with hypertensive blood levels would be falsely reassured that their blood pressure was in the normal range.

His team’s 2023 review of the current landscape, which includes more sophisticated devices, concluded that accuracy remains an issue: “Unfortunately, the pace of regulation of these devices has failed to match the speed of innovation and direct availability to patient consumers. There is an urgent need to develop a consensus on standards by which cuffless BP devices can be tested for accuracy.”
 

Devices, indications differ

Cuffless devices estimate blood pressure indirectly. Most operate based on pulse wave analysis and pulse arrival time (PWA-PAT), explained Ramakrishna Mukkamala, PhD, in a commentary. Dr. Mukkamala is a professor in the departments of bioengineering and anesthesiology and perioperative medicine at the University of Pittsburgh.

PWA involves measuring a peripheral arterial waveform using an optical sensor such as the green lights on the back of a wrist-worn device, or a ‘force sensor’ such as a finger cuff or pressing on a smartphone. Certain features are extracted from the waveform using machine learning and calibrated to blood pressure values.

PAT techniques work together with PWA; they record the ECG and extract features from that signal as well as the arterial waveform for calibration to blood pressure values.

The algorithm used to generate the BP numbers comprises a proprietary baseline model that may include demographics and other patient characteristics. A cuff measurement is often part of the baseline model because most cuffless devices require periodic (typically weekly or monthly) calibration using a cuffed device.

Cuffless devices that require cuff calibration compare the estimate they get to the cuff-calibrated number. In this scenario, the cuffless device may come up with the same blood pressure numbers simply because the baseline model – which is made up of thousands of data points relevant to the patient – has not changed.

This has led some experts to question whether PWA-PAT cuffless device readings actually add anything to the baseline model.

They don’t, according to Microsoft Research in what Dr. Mukkamala and coauthors referred to (in a review published in Hypertension) as “a complex article describing perhaps the most important and highest resource project to date (Aurora Project) on assessing the accuracy of PWA and PWA devices.”

The Microsoft article was written for bioengineers. The review in Hypertension explains the project for clinicians, and concludes that, “Cuffless BP devices based on PWA and PWA-PAT, which are similar to some regulatory-cleared devices, were of no additional value in measuring auscultatory or 24-hour ambulatory cuff BP when compared with a baseline model in which BP was predicted without an actual measurement.”
 

IEEE and FDA validation

Despite these concerns, several cuffless devices using PWA and PAT have been cleared by the Food and Drug Administration.

Validating cuffless devices is no simple matter. The Institute of Electrical and Electronics Engineers published a validation protocol for cuffless blood pressure devices in 2014 that was amended in 2019 to include a requirement to evaluate performance in different positions and in the presence of motion with varying degrees of noise artifact.

However, Daichi Shimbo, MD, codirector of the Columbia Hypertension Center in New York and vice chair of the American Heart Association Statement on blood pressure monitoring, and colleagues point out limitations, even in the updated standard. These include not requiring evaluation for drift over time; lack of specific dynamic testing protocols for stressors such as exercise or environmental temperatures; and an unsuitable reference standard (oscillometric cuff-based devices) during movement.

Dr. Shimbo said in an interview that, although he is excited about them, “these cuffless devices are not aligned with regulatory bodies. If a device gives someone a wrong blood pressure, they might be diagnosed with hypertension when they don’t have it or might miss the fact that they’re hypertensive because they get a normal blood pressure reading. If there’s no yardstick by which you say these devices are good, what are we really doing – helping, or causing a problem?”

“The specifics of how a device estimates blood pressure can determine what testing is needed to ensure that it is providing accurate performance in the intended conditions of use,” Jeremy Kahn, an FDA press officer, said in an interview. “For example, for cuffless devices that are calibrated initially with a cuff-based blood pressure device, the cuffless device needs to specify the period over which it can provide accurate readings and have testing to demonstrate that it provides accurate results over that period of use.”

The FDA said its testing is different from what the Microsoft Aurora Project used in their study.

“The intent of that testing, as the agency understands it, is to evaluate whether the device is providing useful input based on the current physiology of the patient rather than relying on predetermined values based on calibration or patient attributes. We evaluate this clinically in two separate tests: an induced change in blood pressure test and tracking of natural blood pressure changes with longer term device use,” Mr. Kahn explained.

Analyzing a device’s performance on individuals who have had natural changes in blood pressure as compared to a calibration value or initial reading “can also help discern if the device is using physiological data from the patient to determine their blood pressure accurately,” he said.

Experts interviewed for this article who remain skeptical about cuffless BP monitoring question whether the numbers that appear during the induced blood pressure change, and with the natural blood pressure changes that may occur over time, accurately reflect a patient’s blood pressure.

“The FDA doesn’t approve these devices; they clear them,” Dr. Shimbo pointed out. “Clearing them means they can be sold to the general public in the U.S. It’s not a strong statement that they’re accurate.”
 

Moving toward validation, standards

Ultimately, cuffless BP monitors may require more than one validation protocol and standard, depending on their technology, how and where they will be used, and by whom.

And as Dr. Plante and colleagues write, “Importantly, validation should be performed in diverse and special populations, including pregnant women and individuals across a range of heart rates, skin tones, wrist sizes, common arrhythmias, and beta-blocker use.”

Organizations that might be expected to help move validation and standards forward have mostly remained silent. The American Medical Association’s US Blood Pressure Validated Device Listing website includes only cuffed devices, as does the website of the international scientific nonprofit STRIDE BP.

The European Society of Hypertension 2022 consensus statement on cuffless devices concluded that, until there is an internationally accepted accuracy standard and the devices have been tested in healthy people and those with suspected or diagnosed hypertension, “cuffless BP devices should not be used for the evaluation or management of hypertension in clinical practice.”

This month, ESH published recommendations for “specific, clinically meaningful, and pragmatic validation procedures for different types of intermittent cuffless devices” that will be presented at their upcoming annual meeting June 26.

Updated protocols from IEEE “are coming out soon,” according to Dr. Shimbo. The FDA says currently cleared devices won’t need to revalidate according to new standards unless the sponsor makes significant modifications in software algorithms, device hardware, or targeted patient populations.
 

Device makers take the initiative

In the face of conflicting reports on accuracy and lack of a robust standard, some device makers are publishing their own tests or encouraging validation by potential customers.

For example, institutions that are considering using the Biobeat cuffless blood pressure monitor watch “usually start with small pilots with our devices to do internal validation,” Lior Ben Shettrit, the company’s vice president of business development, said in an interview. “Only after they complete the internal validation are they willing to move forward to full implementation.”

Cardiologist Dean Nachman, MD, is leading validation studies of the Biobeat device at the Hadassah Ein Kerem Medical Center in Jerusalem. For the first validation, the team recruited 1,057 volunteers who did a single blood pressure measurement with the cuffless device and with a cuffed device.

“We found 96.3% agreement in identifying hypertension and an interclass correlation coefficient of 0.99 and 0.97 for systolic and diastolic measurements, respectively,” he said. “Then we took it to the next level and compared the device to ambulatory 24-hour blood pressure monitoring and found comparable measurements.”

The investigators are not done yet. “We need data from thousands of patients, with subgroups, to not have any concerns,” he says. “Right now, we are using the device as a general monitor – as an EKG plus heart rate plus oxygen saturation level monitor – and as a blood pressure monitor for 24-hour blood pressure monitoring.”

The developers of the Aktiia device, which is the one Dr. Topol tested, take a different perspective. “When somebody introduces a new technology that is disrupting something that has been in place for over 100 years, there will always be some grumblings, ruffling of feathers, people saying it’s not ready, it’s not ready, it’s not ready,” Aktiia’s chief medical officer Jay Shah, MD, noted.

“But a lot of those comments are coming from the isolation of an ivory tower,” he said.

Aktiia cofounder and chief technology officer Josep Solà said that “no device is probably as accurate as if you have an invasive catheter,” adding that “we engage patients to look at their blood pressure day by day. … If each individual measurement of each of those patient is slightly less accurate than a cuff, who cares? We have 40 measurements per day on each patient. The accuracy and precision of each of those is good.”

Researchers from the George Institute for Global Health recently compared the Aktiia device to conventional ambulatory monitoring in 41 patients and found that “it did not accurately track night-time BP decline and results suggested it was unable to track medication-induced BP changes.”

“In the context of 24/7 monitoring of hypertensive patients,” Mr. Solà said, “whatever you do, if it’s better than a sham device or a baseline model and you track the blood pressure changes, it’s a hundred times much better than doing nothing.”

Dr. Nachman and Dr. Plante reported no relevant financial relationships. Dr. Shimbo reported that he received funding from NIH and has consulted for Abbott Vascular, Edward Lifesciences, Medtronic, and Tryton Medical.