Conference Coverage

As a physician in the heart of the opioid epidemic, Pavirthra R. Ellison, MD, has watched for years as her patients have lost parents to overdoses. More than 1,400 adults in West Virginia, where she practices, died of opioid abuse in 2021 alone, government statistics show.

The grim toll made Ellison wonder: What was happening to children in the state? The answer, according to a new study, is not reassuring.

Ellison and her colleagues have found a troubling link between a surge in critical head and neck injuries among youth in West Virginia and a spike in positive tests for opioids and benzodiazepines among children who arrive at emergency departments in the state. They don’t think the pattern is a coincidence.

“What we found was really kind of scary,” said Dr. Ellison, a professor of anesthesiology and pediatrics at West Virginia University, Morgantown. “Children in this region often get exposure to these drugs early on.”
 

A region in crisis

According to a 2020 report from the Department of Health & Human Services, about 9.9 million Americans abused prescription opioids in 2018. That same year, almost 47,000 died following an overdose of the painkillers. In 2017, Appalachian counties experienced a death rate from opioid overdoses that was 72% higher than that of the rest of the country.

Dr. Ellison and associates who presented their findings recently at the 2022 annual meeting of the American Society of Anesthesiologists, examined rates of pediatric trauma injuries, injury severity, and results of drug screenings throughout West Virginia between 2009 and 2019.

The study included 4,538 children and adolescents younger than 18 years who had been treated for head and neck trauma. The youth were divided into two groups: 3,356 who were treated from 2009 to 2016, and 1,182 who were treated between 2017 and 2019.

The incidence of critical head injuries increased from 3.7% in the period 2009-2016 to 7.2% in the period 2017-2019 (P = .007). The incidence of serious neck injuries increased from 12.2% to 27.1% (P = .007) during that period, according to the researchers. The number of days that these patients spent on ventilators more than doubled, from 3.1 to 6.3 (P < .001), they reported.

At the same time, the rate of positive urine drug tests rose sharply, from 0.8% to 1.8% (P < .001) for benzodiazepines and from 1% to 4.9% for opioids (P < .001).

Drug testing of children hospitalized for trauma rose more than threefold, from 6.9% to 23.2% (P < .001). Dr. Ellison’s group was unable to match positive drug screens with patients who came in with injuries.

Dr. Ellison said her research “warrants further evaluation of current policies and protocols targeting substance use in children and adolescents.” To that end, her team is planning to conduct a prospective study in mid 2023 to further illuminate the trends.

“I hope early next year we can put together a group of physicians, pediatric general surgeons, neurosurgeons, and anesthesiologists,” she said. “I want to look at what we can do to reduce the severity of injury.”

She also wants to reach the population that these findings directly affect.

“The next step that we are currently working on is community awareness of the issue,” Dr. Ellison said. “Our trauma institute is partnering with middle school and high school kids to create material to raise awareness.”

Rural Appalachia faces several other endemic problems that affect the health and well-being of children and families, including limited access to health care, poverty, and minimal community support, according to Dr. Ellison. Children and teens in the region who live with parents who abuse opioids are more likely to experience family conflict, mental health challenges, legal troubles, and negative health effects, including physical trauma.
 

A call to action

Toufic Jildeh, MD, assistant professor of orthopedics, Michigan State University Health Care, East Lansing, who has studied ways to reduce opioid use among surgery patients, called the new findings “alarming.”

After reviewing the study, Dr. Jildeh said that in his opinion, the results support standardized drug testing of children, particularly in the context of severe trauma.

Bruce Bassi, MD, an addiction psychiatrist and owner of TelepsychHealth, a private, online psychiatric practice, agreed. “The main take-home message is that drug screening should be the standard of care for pediatric patients in this region, because it changes the management of those individuals,” Dr. Bassi said.

But identifying these patients is just the first step. “We should continue to educate and raise awareness, not only in the health care system,” Dr. Bassi said. “We also need to let parents know that the possibility of children obtaining access to medications is high.”

The study was independently supported. Dr. Ellison and Dr. Jildeh reported no relevant financial relationships. Dr. Bassi owns a private psychiatry practice called Telepsychhealth but has no other relevant financial relationships.

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

As a physician in the heart of the opioid epidemic, Pavirthra R. Ellison, MD, has watched for years as her patients have lost parents to overdoses. More than 1,400 adults in West Virginia, where she practices, died of opioid abuse in 2021 alone, government statistics show.

The grim toll made Ellison wonder: What was happening to children in the state? The answer, according to a new study, is not reassuring.

Ellison and her colleagues have found a troubling link between a surge in critical head and neck injuries among youth in West Virginia and a spike in positive tests for opioids and benzodiazepines among children who arrive at emergency departments in the state. They don’t think the pattern is a coincidence.

“What we found was really kind of scary,” said Dr. Ellison, a professor of anesthesiology and pediatrics at West Virginia University, Morgantown. “Children in this region often get exposure to these drugs early on.”
 

A region in crisis

According to a 2020 report from the Department of Health & Human Services, about 9.9 million Americans abused prescription opioids in 2018. That same year, almost 47,000 died following an overdose of the painkillers. In 2017, Appalachian counties experienced a death rate from opioid overdoses that was 72% higher than that of the rest of the country.

Dr. Ellison and associates who presented their findings recently at the 2022 annual meeting of the American Society of Anesthesiologists, examined rates of pediatric trauma injuries, injury severity, and results of drug screenings throughout West Virginia between 2009 and 2019.

The study included 4,538 children and adolescents younger than 18 years who had been treated for head and neck trauma. The youth were divided into two groups: 3,356 who were treated from 2009 to 2016, and 1,182 who were treated between 2017 and 2019.

The incidence of critical head injuries increased from 3.7% in the period 2009-2016 to 7.2% in the period 2017-2019 (P = .007). The incidence of serious neck injuries increased from 12.2% to 27.1% (P = .007) during that period, according to the researchers. The number of days that these patients spent on ventilators more than doubled, from 3.1 to 6.3 (P < .001), they reported.

At the same time, the rate of positive urine drug tests rose sharply, from 0.8% to 1.8% (P < .001) for benzodiazepines and from 1% to 4.9% for opioids (P < .001).

Drug testing of children hospitalized for trauma rose more than threefold, from 6.9% to 23.2% (P < .001). Dr. Ellison’s group was unable to match positive drug screens with patients who came in with injuries.

Dr. Ellison said her research “warrants further evaluation of current policies and protocols targeting substance use in children and adolescents.” To that end, her team is planning to conduct a prospective study in mid 2023 to further illuminate the trends.

“I hope early next year we can put together a group of physicians, pediatric general surgeons, neurosurgeons, and anesthesiologists,” she said. “I want to look at what we can do to reduce the severity of injury.”

She also wants to reach the population that these findings directly affect.

“The next step that we are currently working on is community awareness of the issue,” Dr. Ellison said. “Our trauma institute is partnering with middle school and high school kids to create material to raise awareness.”

Rural Appalachia faces several other endemic problems that affect the health and well-being of children and families, including limited access to health care, poverty, and minimal community support, according to Dr. Ellison. Children and teens in the region who live with parents who abuse opioids are more likely to experience family conflict, mental health challenges, legal troubles, and negative health effects, including physical trauma.
 

A call to action

Toufic Jildeh, MD, assistant professor of orthopedics, Michigan State University Health Care, East Lansing, who has studied ways to reduce opioid use among surgery patients, called the new findings “alarming.”

After reviewing the study, Dr. Jildeh said that in his opinion, the results support standardized drug testing of children, particularly in the context of severe trauma.

Bruce Bassi, MD, an addiction psychiatrist and owner of TelepsychHealth, a private, online psychiatric practice, agreed. “The main take-home message is that drug screening should be the standard of care for pediatric patients in this region, because it changes the management of those individuals,” Dr. Bassi said.

But identifying these patients is just the first step. “We should continue to educate and raise awareness, not only in the health care system,” Dr. Bassi said. “We also need to let parents know that the possibility of children obtaining access to medications is high.”

The study was independently supported. Dr. Ellison and Dr. Jildeh reported no relevant financial relationships. Dr. Bassi owns a private psychiatry practice called Telepsychhealth but has no other relevant financial relationships.

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

As a physician in the heart of the opioid epidemic, Pavirthra R. Ellison, MD, has watched for years as her patients have lost parents to overdoses. More than 1,400 adults in West Virginia, where she practices, died of opioid abuse in 2021 alone, government statistics show.

The grim toll made Ellison wonder: What was happening to children in the state? The answer, according to a new study, is not reassuring.

Ellison and her colleagues have found a troubling link between a surge in critical head and neck injuries among youth in West Virginia and a spike in positive tests for opioids and benzodiazepines among children who arrive at emergency departments in the state. They don’t think the pattern is a coincidence.

“What we found was really kind of scary,” said Dr. Ellison, a professor of anesthesiology and pediatrics at West Virginia University, Morgantown. “Children in this region often get exposure to these drugs early on.”
 

A region in crisis

According to a 2020 report from the Department of Health & Human Services, about 9.9 million Americans abused prescription opioids in 2018. That same year, almost 47,000 died following an overdose of the painkillers. In 2017, Appalachian counties experienced a death rate from opioid overdoses that was 72% higher than that of the rest of the country.

Dr. Ellison and associates who presented their findings recently at the 2022 annual meeting of the American Society of Anesthesiologists, examined rates of pediatric trauma injuries, injury severity, and results of drug screenings throughout West Virginia between 2009 and 2019.

The study included 4,538 children and adolescents younger than 18 years who had been treated for head and neck trauma. The youth were divided into two groups: 3,356 who were treated from 2009 to 2016, and 1,182 who were treated between 2017 and 2019.

The incidence of critical head injuries increased from 3.7% in the period 2009-2016 to 7.2% in the period 2017-2019 (P = .007). The incidence of serious neck injuries increased from 12.2% to 27.1% (P = .007) during that period, according to the researchers. The number of days that these patients spent on ventilators more than doubled, from 3.1 to 6.3 (P < .001), they reported.

At the same time, the rate of positive urine drug tests rose sharply, from 0.8% to 1.8% (P < .001) for benzodiazepines and from 1% to 4.9% for opioids (P < .001).

Drug testing of children hospitalized for trauma rose more than threefold, from 6.9% to 23.2% (P < .001). Dr. Ellison’s group was unable to match positive drug screens with patients who came in with injuries.

Dr. Ellison said her research “warrants further evaluation of current policies and protocols targeting substance use in children and adolescents.” To that end, her team is planning to conduct a prospective study in mid 2023 to further illuminate the trends.

“I hope early next year we can put together a group of physicians, pediatric general surgeons, neurosurgeons, and anesthesiologists,” she said. “I want to look at what we can do to reduce the severity of injury.”

She also wants to reach the population that these findings directly affect.

“The next step that we are currently working on is community awareness of the issue,” Dr. Ellison said. “Our trauma institute is partnering with middle school and high school kids to create material to raise awareness.”

Rural Appalachia faces several other endemic problems that affect the health and well-being of children and families, including limited access to health care, poverty, and minimal community support, according to Dr. Ellison. Children and teens in the region who live with parents who abuse opioids are more likely to experience family conflict, mental health challenges, legal troubles, and negative health effects, including physical trauma.
 

A call to action

Toufic Jildeh, MD, assistant professor of orthopedics, Michigan State University Health Care, East Lansing, who has studied ways to reduce opioid use among surgery patients, called the new findings “alarming.”

After reviewing the study, Dr. Jildeh said that in his opinion, the results support standardized drug testing of children, particularly in the context of severe trauma.

Bruce Bassi, MD, an addiction psychiatrist and owner of TelepsychHealth, a private, online psychiatric practice, agreed. “The main take-home message is that drug screening should be the standard of care for pediatric patients in this region, because it changes the management of those individuals,” Dr. Bassi said.

But identifying these patients is just the first step. “We should continue to educate and raise awareness, not only in the health care system,” Dr. Bassi said. “We also need to let parents know that the possibility of children obtaining access to medications is high.”

The study was independently supported. Dr. Ellison and Dr. Jildeh reported no relevant financial relationships. Dr. Bassi owns a private psychiatry practice called Telepsychhealth but has no other relevant financial relationships.

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

Use of a combination antihypertensive product containing quarter doses of four different drugs could be an effective strategy to get patients to target blood pressures in one step, a new study suggests. 

The study, QUARTET-USA, showed a reduction in BP of almost 5 mm Hg more than the comparator of one antihypertensive agent at standard dose over the 12-week follow-up period in patients with mild to moderate hypertension.

The QUARTET-USA study was presented at the American Heart Association scientific sessions by Mark Huffman, MD, professor of medicine at Washington University in St. Louis. 

It builds on a previous trial, QUARTET, conducted in Australia, which first showed benefits with this approach.

In the new U.S. study, which was considerably smaller than the Australian trial, the four-drug combination, including candesartan, amlodipine, indapamide, and bisoprolol, led to a –4.8/–4.9 mm Hg greater reduction in BP from baseline to 12 weeks, compared with standard-dose candesartan monotherapy.

Differences in systolic BP were not statistically significant, which is likely because of limited power related to the sample size, Dr. Huffman noted.

Adverse events were more common in the four-drug intervention group, but the rate of discontinuation was higher in the comparator group. No severe adverse events were deemed related to the study drug.

“The direction and magnitude of [the] blood pressure–lowering effect were similar between the previous Australian study and this American study, despite different populations with lower baseline blood pressure in the current study, thus strengthening the case for this new approach,” Dr. Huffman concluded.

“The two studies together show that the approach of using four drugs in quarter doses is more effective in lowering blood pressure than a single standard dose antihypertensive agent and has an acceptable safely profile,” he said in an interview.

He said the four-drug combination could be an effective way of getting patients to target without multiple appointments.

“If you think about how many visits to the doctor’s office it takes to get patients to goal blood pressures, this combination gets patients down to new guideline target levels in one step, whereas in the SPRINT trial it took three or more visits to get down to these levels. And in practice we lose people – they don’t come back,” he said.

Dr. Huffman explained that the rationale for the study was the persistently low hypertension control rate, which demonstrates the need for a new approach.

The previous Australian QUARTET study suggested that ultra–low-dose combination therapy has a favorable balance between blood pressure–lowering effect, tolerability, and adherence.

That study, conducted in 591 patients and reported in 2021, demonstrated a greater BP-lowering effect with a four-drug combination at quarter doses (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) at 12 weeks, compared with irbesartan 150 mg daily. Systolic BP was reduced by more than 6.9 mm Hg and diastolic BP by 5.8 mm Hg than full-dose irbesartan alone, both significant differences.

The current study, QUARTET-USA, aimed to see if a similar strategy could produce comparable results in a U.S. population.

The U.S. study included 62 patients from the Access Community Health Network, Chicago, who were either treatment naive with BPs above 140/90 mm Hg, or already taking antihypertensive monotherapy with BPs above 130/85 mm Hg.

The mean systolic BP at baseline was 138 mm Hg and the mean diastolic pressure was 84 mm Hg.

Study participants were mainly from ethnic minorities (90% Hispanic or Black) and over half were from low-income households (annual household income less than $25,000).

They were randomly assigned to daily administration of a four-drug combination at quarter doses (candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) or a full dose of candesartan 8 mg (the comparator arm).

Amlodipine 5 mg daily could be added on to treatment if BP remained above 130/80 mm Hg at 6 weeks. This occurred in 18% of the study group versus 53% of the comparator group.

Results showed that at 12 weeks the adjusted mean change in systolic BP weeks was –4.8 mm Hg (95% CI,–10.7 to 1.2), and the adjusted mean change in diastolic BP was –4.9 mm Hg (95% CI, –8.6 to –1.1) in the four-drug combination group, compared with the comparator arm.

Average BPs at the end of 12-week study period were 121 mm Hg systolic and 73 mm Hg diastolic in the four-drug intervention group, compared with 124 mm Hg systolic and 77 mm Hg diastolic in the comparator group.

Any adverse events that were possibly related to drug therapy occurred in 25% of the intervention group versus 10% of the comparator group. But adverse events leading to discontinuation occurred in 6.3% of the study group versus 26.7% of patients in the comparator arm.

“New approaches are needed to achieve lower blood pressure targets, especially for patients and communities with a high burden of hypertension and hypertension-related diseases. QUARTET-USA was the first trial of a four-drug, ultra–low-dose, blood pressure–lowering combination therapy in the U.S.,” Dr. Huffman said.

“We showed reductions in blood pressure similar in magnitude to those in the Australian study. It is useful to know that the direction of the effect is similar across varied populations. Now that we have that signal of efficacy and tolerability, we can move to actually getting it into the hands of patients and providers,” he added.

Noting that further studies will be required to attain marketing authorization, Dr. Huffman suggested that a pharmaceutical company would need to complete that process.

“These are promising results for companies who may be interested in partnering,” he said.

‘A more efficient approach’ 

LaPrincess C. Brewer, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minn., and discussant of the study, said the QUARTET-USA study suggests the four-drug, low-dose combination shows promise in lowering BP, compared with the standard dose, and while the reduction in systolic BP was not quite significant, it was clinically meaningful.

“Most U.S. adults with hypertension do not have it under control. This is due to unfavorable social and structural determinants of health which limit adherence to antihypertensive medication,” Dr. Brewer noted.  

From a patient point of view, the multiple visits needed to attain goals are a burden and there is also the issue of clinical inertia and lack of medication intensification by clinicians, she commented. 

“Of patients with uncontrolled hypertension, 40% are taking just one antihypertensive medication, so up-front, low-dose combination therapy is likely a more efficient approach,” she said.

“This study builds the evidence base for the need for tailored interventions that address the social determinants of health and the intentional prioritization of diverse population in clinical trials,” Dr. Brewer concluded.

QUARTET was an investigator-initiated study, Dr. Huffman reported a pending patent for a heart failure polypill. The George Institute for Global Health, Sydney, Australia, where Huffman has a secondary appointment, has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy. Dr. Brewer reported research support from the National Institutes of Health, Centers for Disease Control and Prevention, American Heart Association, and Bristol-Meyers Squibb Foundation.

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

Use of a combination antihypertensive product containing quarter doses of four different drugs could be an effective strategy to get patients to target blood pressures in one step, a new study suggests. 

The study, QUARTET-USA, showed a reduction in BP of almost 5 mm Hg more than the comparator of one antihypertensive agent at standard dose over the 12-week follow-up period in patients with mild to moderate hypertension.

The QUARTET-USA study was presented at the American Heart Association scientific sessions by Mark Huffman, MD, professor of medicine at Washington University in St. Louis. 

It builds on a previous trial, QUARTET, conducted in Australia, which first showed benefits with this approach.

In the new U.S. study, which was considerably smaller than the Australian trial, the four-drug combination, including candesartan, amlodipine, indapamide, and bisoprolol, led to a –4.8/–4.9 mm Hg greater reduction in BP from baseline to 12 weeks, compared with standard-dose candesartan monotherapy.

Differences in systolic BP were not statistically significant, which is likely because of limited power related to the sample size, Dr. Huffman noted.

Adverse events were more common in the four-drug intervention group, but the rate of discontinuation was higher in the comparator group. No severe adverse events were deemed related to the study drug.

“The direction and magnitude of [the] blood pressure–lowering effect were similar between the previous Australian study and this American study, despite different populations with lower baseline blood pressure in the current study, thus strengthening the case for this new approach,” Dr. Huffman concluded.

“The two studies together show that the approach of using four drugs in quarter doses is more effective in lowering blood pressure than a single standard dose antihypertensive agent and has an acceptable safely profile,” he said in an interview.

He said the four-drug combination could be an effective way of getting patients to target without multiple appointments.

“If you think about how many visits to the doctor’s office it takes to get patients to goal blood pressures, this combination gets patients down to new guideline target levels in one step, whereas in the SPRINT trial it took three or more visits to get down to these levels. And in practice we lose people – they don’t come back,” he said.

Dr. Huffman explained that the rationale for the study was the persistently low hypertension control rate, which demonstrates the need for a new approach.

The previous Australian QUARTET study suggested that ultra–low-dose combination therapy has a favorable balance between blood pressure–lowering effect, tolerability, and adherence.

That study, conducted in 591 patients and reported in 2021, demonstrated a greater BP-lowering effect with a four-drug combination at quarter doses (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) at 12 weeks, compared with irbesartan 150 mg daily. Systolic BP was reduced by more than 6.9 mm Hg and diastolic BP by 5.8 mm Hg than full-dose irbesartan alone, both significant differences.

The current study, QUARTET-USA, aimed to see if a similar strategy could produce comparable results in a U.S. population.

The U.S. study included 62 patients from the Access Community Health Network, Chicago, who were either treatment naive with BPs above 140/90 mm Hg, or already taking antihypertensive monotherapy with BPs above 130/85 mm Hg.

The mean systolic BP at baseline was 138 mm Hg and the mean diastolic pressure was 84 mm Hg.

Study participants were mainly from ethnic minorities (90% Hispanic or Black) and over half were from low-income households (annual household income less than $25,000).

They were randomly assigned to daily administration of a four-drug combination at quarter doses (candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) or a full dose of candesartan 8 mg (the comparator arm).

Amlodipine 5 mg daily could be added on to treatment if BP remained above 130/80 mm Hg at 6 weeks. This occurred in 18% of the study group versus 53% of the comparator group.

Results showed that at 12 weeks the adjusted mean change in systolic BP weeks was –4.8 mm Hg (95% CI,–10.7 to 1.2), and the adjusted mean change in diastolic BP was –4.9 mm Hg (95% CI, –8.6 to –1.1) in the four-drug combination group, compared with the comparator arm.

Average BPs at the end of 12-week study period were 121 mm Hg systolic and 73 mm Hg diastolic in the four-drug intervention group, compared with 124 mm Hg systolic and 77 mm Hg diastolic in the comparator group.

Any adverse events that were possibly related to drug therapy occurred in 25% of the intervention group versus 10% of the comparator group. But adverse events leading to discontinuation occurred in 6.3% of the study group versus 26.7% of patients in the comparator arm.

“New approaches are needed to achieve lower blood pressure targets, especially for patients and communities with a high burden of hypertension and hypertension-related diseases. QUARTET-USA was the first trial of a four-drug, ultra–low-dose, blood pressure–lowering combination therapy in the U.S.,” Dr. Huffman said.

“We showed reductions in blood pressure similar in magnitude to those in the Australian study. It is useful to know that the direction of the effect is similar across varied populations. Now that we have that signal of efficacy and tolerability, we can move to actually getting it into the hands of patients and providers,” he added.

Noting that further studies will be required to attain marketing authorization, Dr. Huffman suggested that a pharmaceutical company would need to complete that process.

“These are promising results for companies who may be interested in partnering,” he said.

‘A more efficient approach’ 

LaPrincess C. Brewer, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minn., and discussant of the study, said the QUARTET-USA study suggests the four-drug, low-dose combination shows promise in lowering BP, compared with the standard dose, and while the reduction in systolic BP was not quite significant, it was clinically meaningful.

“Most U.S. adults with hypertension do not have it under control. This is due to unfavorable social and structural determinants of health which limit adherence to antihypertensive medication,” Dr. Brewer noted.  

From a patient point of view, the multiple visits needed to attain goals are a burden and there is also the issue of clinical inertia and lack of medication intensification by clinicians, she commented. 

“Of patients with uncontrolled hypertension, 40% are taking just one antihypertensive medication, so up-front, low-dose combination therapy is likely a more efficient approach,” she said.

“This study builds the evidence base for the need for tailored interventions that address the social determinants of health and the intentional prioritization of diverse population in clinical trials,” Dr. Brewer concluded.

QUARTET was an investigator-initiated study, Dr. Huffman reported a pending patent for a heart failure polypill. The George Institute for Global Health, Sydney, Australia, where Huffman has a secondary appointment, has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy. Dr. Brewer reported research support from the National Institutes of Health, Centers for Disease Control and Prevention, American Heart Association, and Bristol-Meyers Squibb Foundation.

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

Use of a combination antihypertensive product containing quarter doses of four different drugs could be an effective strategy to get patients to target blood pressures in one step, a new study suggests. 

The study, QUARTET-USA, showed a reduction in BP of almost 5 mm Hg more than the comparator of one antihypertensive agent at standard dose over the 12-week follow-up period in patients with mild to moderate hypertension.

The QUARTET-USA study was presented at the American Heart Association scientific sessions by Mark Huffman, MD, professor of medicine at Washington University in St. Louis. 

It builds on a previous trial, QUARTET, conducted in Australia, which first showed benefits with this approach.

In the new U.S. study, which was considerably smaller than the Australian trial, the four-drug combination, including candesartan, amlodipine, indapamide, and bisoprolol, led to a –4.8/–4.9 mm Hg greater reduction in BP from baseline to 12 weeks, compared with standard-dose candesartan monotherapy.

Differences in systolic BP were not statistically significant, which is likely because of limited power related to the sample size, Dr. Huffman noted.

Adverse events were more common in the four-drug intervention group, but the rate of discontinuation was higher in the comparator group. No severe adverse events were deemed related to the study drug.

“The direction and magnitude of [the] blood pressure–lowering effect were similar between the previous Australian study and this American study, despite different populations with lower baseline blood pressure in the current study, thus strengthening the case for this new approach,” Dr. Huffman concluded.

“The two studies together show that the approach of using four drugs in quarter doses is more effective in lowering blood pressure than a single standard dose antihypertensive agent and has an acceptable safely profile,” he said in an interview.

He said the four-drug combination could be an effective way of getting patients to target without multiple appointments.

“If you think about how many visits to the doctor’s office it takes to get patients to goal blood pressures, this combination gets patients down to new guideline target levels in one step, whereas in the SPRINT trial it took three or more visits to get down to these levels. And in practice we lose people – they don’t come back,” he said.

Dr. Huffman explained that the rationale for the study was the persistently low hypertension control rate, which demonstrates the need for a new approach.

The previous Australian QUARTET study suggested that ultra–low-dose combination therapy has a favorable balance between blood pressure–lowering effect, tolerability, and adherence.

That study, conducted in 591 patients and reported in 2021, demonstrated a greater BP-lowering effect with a four-drug combination at quarter doses (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) at 12 weeks, compared with irbesartan 150 mg daily. Systolic BP was reduced by more than 6.9 mm Hg and diastolic BP by 5.8 mm Hg than full-dose irbesartan alone, both significant differences.

The current study, QUARTET-USA, aimed to see if a similar strategy could produce comparable results in a U.S. population.

The U.S. study included 62 patients from the Access Community Health Network, Chicago, who were either treatment naive with BPs above 140/90 mm Hg, or already taking antihypertensive monotherapy with BPs above 130/85 mm Hg.

The mean systolic BP at baseline was 138 mm Hg and the mean diastolic pressure was 84 mm Hg.

Study participants were mainly from ethnic minorities (90% Hispanic or Black) and over half were from low-income households (annual household income less than $25,000).

They were randomly assigned to daily administration of a four-drug combination at quarter doses (candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) or a full dose of candesartan 8 mg (the comparator arm).

Amlodipine 5 mg daily could be added on to treatment if BP remained above 130/80 mm Hg at 6 weeks. This occurred in 18% of the study group versus 53% of the comparator group.

Results showed that at 12 weeks the adjusted mean change in systolic BP weeks was –4.8 mm Hg (95% CI,–10.7 to 1.2), and the adjusted mean change in diastolic BP was –4.9 mm Hg (95% CI, –8.6 to –1.1) in the four-drug combination group, compared with the comparator arm.

Average BPs at the end of 12-week study period were 121 mm Hg systolic and 73 mm Hg diastolic in the four-drug intervention group, compared with 124 mm Hg systolic and 77 mm Hg diastolic in the comparator group.

Any adverse events that were possibly related to drug therapy occurred in 25% of the intervention group versus 10% of the comparator group. But adverse events leading to discontinuation occurred in 6.3% of the study group versus 26.7% of patients in the comparator arm.

“New approaches are needed to achieve lower blood pressure targets, especially for patients and communities with a high burden of hypertension and hypertension-related diseases. QUARTET-USA was the first trial of a four-drug, ultra–low-dose, blood pressure–lowering combination therapy in the U.S.,” Dr. Huffman said.

“We showed reductions in blood pressure similar in magnitude to those in the Australian study. It is useful to know that the direction of the effect is similar across varied populations. Now that we have that signal of efficacy and tolerability, we can move to actually getting it into the hands of patients and providers,” he added.

Noting that further studies will be required to attain marketing authorization, Dr. Huffman suggested that a pharmaceutical company would need to complete that process.

“These are promising results for companies who may be interested in partnering,” he said.

‘A more efficient approach’ 

LaPrincess C. Brewer, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minn., and discussant of the study, said the QUARTET-USA study suggests the four-drug, low-dose combination shows promise in lowering BP, compared with the standard dose, and while the reduction in systolic BP was not quite significant, it was clinically meaningful.

“Most U.S. adults with hypertension do not have it under control. This is due to unfavorable social and structural determinants of health which limit adherence to antihypertensive medication,” Dr. Brewer noted.  

From a patient point of view, the multiple visits needed to attain goals are a burden and there is also the issue of clinical inertia and lack of medication intensification by clinicians, she commented. 

“Of patients with uncontrolled hypertension, 40% are taking just one antihypertensive medication, so up-front, low-dose combination therapy is likely a more efficient approach,” she said.

“This study builds the evidence base for the need for tailored interventions that address the social determinants of health and the intentional prioritization of diverse population in clinical trials,” Dr. Brewer concluded.

QUARTET was an investigator-initiated study, Dr. Huffman reported a pending patent for a heart failure polypill. The George Institute for Global Health, Sydney, Australia, where Huffman has a secondary appointment, has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy. Dr. Brewer reported research support from the National Institutes of Health, Centers for Disease Control and Prevention, American Heart Association, and Bristol-Meyers Squibb Foundation.

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

Nondisabling relapses that occur early in the course of relapsing-remitting multiple sclerosis (RRMS) signal faster accumulation of disability relative to no early relapses, new research suggests. However, in the large registry study, this association was not found in patients treated with high-efficacy, disease-modifying therapies (DMTs) early on.

The results suggest that nondisabling relapses “should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” said lead author Cyrus Daruwalla, MD, department of clinical neurosciences at the University of Cambridge, and Addenbrooke’s Hospital, Cambridge, England.

Dr. Daruwalla presented the findings at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

Questioning EMA restrictions 

“We designed this project because regulators, including EMA [European Medicines Agency], restrict the use of certain DMTs to only those with disabling relapses. In particular, natalizumab [Tysabri] and fingolimod [Gilenya] can only be used as the first-line therapy for people with rapidly evolving, severe MS – which includes having two disabling relapses in a year,” Dr. Daruwalla noted.

“In clinic, when we see somebody who has a nondisabling relapse, we’re left with the question of what is the prognostic significance of that relapse, and how should it influence treatment decisions,” he added.

Using prospectively collected data from the MSBase international registry, the researchers examined data on individuals with RRMS and complete early relapse severity information. 

They compared patients with exclusively nondisabling relapses in the 2 years after definitive RRMS diagnosis with peers with no relapses within this time frame.

To mitigate the confounding effect of DMT use, the investigators performed analyses in participants untreated during follow-up, and then in those who received only older or “platform” therapies (interferon-beta, glatiramer acetate, dimethyl fumarate, or teriflunomide) during follow-up.

In the untreated cohort, 285 patients had nondisabling relapses and 4,717 had no relapses during the 2 years after diagnosis. Those with early nondisabling relapses had a significantly increased risk for disability accumulation (adjusted hazard ratio [aHR], 1.29; 95% confidence interval [CI], 1.00-1.68).

In the treated cohort, 1,074 patients had nondisabling early relapses and 7,262 did not. 

In this cohort, those treated with “platform” DMTs who had nondisabling relapses showed a significantly increased risk for disability accumulation compared with treated peers who had no relapses (aHR, 1.33; 95% CI, 1.15-1.54).

Notably, said Dr. Daruwalla, in patients treated at any point during follow-up with high-efficacy DMTs, including monoclonal antibodies, sphingosphine-1 phosphate modulators, and hematopoietic stem cell transplantation, there was no difference in disability accumulation between patients who did and did not experience nondisabling relapses (aHR, 0.90; 95% CI, 0.71-1.13).

The data clearly show that early nondisabling relapses are associated with a higher risk of disability accumulation than no early relapses in people with relapsing remitting MS,” Dr. Daruwalla said.

However, he noted, treatment with high-efficacy DMTs offers protection against disability accumulations.

“Therefore, contrary to EMA guidance, nondisabling relapses should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” he added.
 

Valuable, confirmatory data

Patricia Coyle, MD, professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University, called the study “valuable.”

“It confirms prior data that having relapses is bad in MS even if they are mild, and provides additional modest data in support of high-efficacy versus moderate-efficacy DMT,” said Dr. Coyle, who was not involved with the research.

“Although certainly not definitive, it adds to data supporting high-efficacy as preferred treatment [and] addresses a completely arbitrary governmental limitation to DMT use in Europe,” she added.

The study had no commercial funding. Dr. Daruwalla has reported no relevant financial relationships. Dr. Coyle reports having received consulting fees from Accordant, Biogen, Bristol-Myers Squibb, Celgene, Genentech/Roche, GlaxoSmithKline, Horizon, Janssen, Novartis, Sanofi Genzyme, and Viela Bio; and grant funding from Actelion, Alkermes, Bristol-Myers Squibb, CorEvitas, Genentech/Roche, Sanofi Genzyme, MedDay, and Novartis.

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

Nondisabling relapses that occur early in the course of relapsing-remitting multiple sclerosis (RRMS) signal faster accumulation of disability relative to no early relapses, new research suggests. However, in the large registry study, this association was not found in patients treated with high-efficacy, disease-modifying therapies (DMTs) early on.

The results suggest that nondisabling relapses “should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” said lead author Cyrus Daruwalla, MD, department of clinical neurosciences at the University of Cambridge, and Addenbrooke’s Hospital, Cambridge, England.

Dr. Daruwalla presented the findings at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

Questioning EMA restrictions 

“We designed this project because regulators, including EMA [European Medicines Agency], restrict the use of certain DMTs to only those with disabling relapses. In particular, natalizumab [Tysabri] and fingolimod [Gilenya] can only be used as the first-line therapy for people with rapidly evolving, severe MS – which includes having two disabling relapses in a year,” Dr. Daruwalla noted.

“In clinic, when we see somebody who has a nondisabling relapse, we’re left with the question of what is the prognostic significance of that relapse, and how should it influence treatment decisions,” he added.

Using prospectively collected data from the MSBase international registry, the researchers examined data on individuals with RRMS and complete early relapse severity information. 

They compared patients with exclusively nondisabling relapses in the 2 years after definitive RRMS diagnosis with peers with no relapses within this time frame.

To mitigate the confounding effect of DMT use, the investigators performed analyses in participants untreated during follow-up, and then in those who received only older or “platform” therapies (interferon-beta, glatiramer acetate, dimethyl fumarate, or teriflunomide) during follow-up.

In the untreated cohort, 285 patients had nondisabling relapses and 4,717 had no relapses during the 2 years after diagnosis. Those with early nondisabling relapses had a significantly increased risk for disability accumulation (adjusted hazard ratio [aHR], 1.29; 95% confidence interval [CI], 1.00-1.68).

In the treated cohort, 1,074 patients had nondisabling early relapses and 7,262 did not. 

In this cohort, those treated with “platform” DMTs who had nondisabling relapses showed a significantly increased risk for disability accumulation compared with treated peers who had no relapses (aHR, 1.33; 95% CI, 1.15-1.54).

Notably, said Dr. Daruwalla, in patients treated at any point during follow-up with high-efficacy DMTs, including monoclonal antibodies, sphingosphine-1 phosphate modulators, and hematopoietic stem cell transplantation, there was no difference in disability accumulation between patients who did and did not experience nondisabling relapses (aHR, 0.90; 95% CI, 0.71-1.13).

The data clearly show that early nondisabling relapses are associated with a higher risk of disability accumulation than no early relapses in people with relapsing remitting MS,” Dr. Daruwalla said.

However, he noted, treatment with high-efficacy DMTs offers protection against disability accumulations.

“Therefore, contrary to EMA guidance, nondisabling relapses should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” he added.
 

Valuable, confirmatory data

Patricia Coyle, MD, professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University, called the study “valuable.”

“It confirms prior data that having relapses is bad in MS even if they are mild, and provides additional modest data in support of high-efficacy versus moderate-efficacy DMT,” said Dr. Coyle, who was not involved with the research.

“Although certainly not definitive, it adds to data supporting high-efficacy as preferred treatment [and] addresses a completely arbitrary governmental limitation to DMT use in Europe,” she added.

The study had no commercial funding. Dr. Daruwalla has reported no relevant financial relationships. Dr. Coyle reports having received consulting fees from Accordant, Biogen, Bristol-Myers Squibb, Celgene, Genentech/Roche, GlaxoSmithKline, Horizon, Janssen, Novartis, Sanofi Genzyme, and Viela Bio; and grant funding from Actelion, Alkermes, Bristol-Myers Squibb, CorEvitas, Genentech/Roche, Sanofi Genzyme, MedDay, and Novartis.

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

Nondisabling relapses that occur early in the course of relapsing-remitting multiple sclerosis (RRMS) signal faster accumulation of disability relative to no early relapses, new research suggests. However, in the large registry study, this association was not found in patients treated with high-efficacy, disease-modifying therapies (DMTs) early on.

The results suggest that nondisabling relapses “should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” said lead author Cyrus Daruwalla, MD, department of clinical neurosciences at the University of Cambridge, and Addenbrooke’s Hospital, Cambridge, England.

Dr. Daruwalla presented the findings at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

Questioning EMA restrictions 

“We designed this project because regulators, including EMA [European Medicines Agency], restrict the use of certain DMTs to only those with disabling relapses. In particular, natalizumab [Tysabri] and fingolimod [Gilenya] can only be used as the first-line therapy for people with rapidly evolving, severe MS – which includes having two disabling relapses in a year,” Dr. Daruwalla noted.

“In clinic, when we see somebody who has a nondisabling relapse, we’re left with the question of what is the prognostic significance of that relapse, and how should it influence treatment decisions,” he added.

Using prospectively collected data from the MSBase international registry, the researchers examined data on individuals with RRMS and complete early relapse severity information. 

They compared patients with exclusively nondisabling relapses in the 2 years after definitive RRMS diagnosis with peers with no relapses within this time frame.

To mitigate the confounding effect of DMT use, the investigators performed analyses in participants untreated during follow-up, and then in those who received only older or “platform” therapies (interferon-beta, glatiramer acetate, dimethyl fumarate, or teriflunomide) during follow-up.

In the untreated cohort, 285 patients had nondisabling relapses and 4,717 had no relapses during the 2 years after diagnosis. Those with early nondisabling relapses had a significantly increased risk for disability accumulation (adjusted hazard ratio [aHR], 1.29; 95% confidence interval [CI], 1.00-1.68).

In the treated cohort, 1,074 patients had nondisabling early relapses and 7,262 did not. 

In this cohort, those treated with “platform” DMTs who had nondisabling relapses showed a significantly increased risk for disability accumulation compared with treated peers who had no relapses (aHR, 1.33; 95% CI, 1.15-1.54).

Notably, said Dr. Daruwalla, in patients treated at any point during follow-up with high-efficacy DMTs, including monoclonal antibodies, sphingosphine-1 phosphate modulators, and hematopoietic stem cell transplantation, there was no difference in disability accumulation between patients who did and did not experience nondisabling relapses (aHR, 0.90; 95% CI, 0.71-1.13).

The data clearly show that early nondisabling relapses are associated with a higher risk of disability accumulation than no early relapses in people with relapsing remitting MS,” Dr. Daruwalla said.

However, he noted, treatment with high-efficacy DMTs offers protection against disability accumulations.

“Therefore, contrary to EMA guidance, nondisabling relapses should be considered in decisions to initiate or escalate treatment, including with high-efficacy therapies,” he added.
 

Valuable, confirmatory data

Patricia Coyle, MD, professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University, called the study “valuable.”

“It confirms prior data that having relapses is bad in MS even if they are mild, and provides additional modest data in support of high-efficacy versus moderate-efficacy DMT,” said Dr. Coyle, who was not involved with the research.

“Although certainly not definitive, it adds to data supporting high-efficacy as preferred treatment [and] addresses a completely arbitrary governmental limitation to DMT use in Europe,” she added.

The study had no commercial funding. Dr. Daruwalla has reported no relevant financial relationships. Dr. Coyle reports having received consulting fees from Accordant, Biogen, Bristol-Myers Squibb, Celgene, Genentech/Roche, GlaxoSmithKline, Horizon, Janssen, Novartis, Sanofi Genzyme, and Viela Bio; and grant funding from Actelion, Alkermes, Bristol-Myers Squibb, CorEvitas, Genentech/Roche, Sanofi Genzyme, MedDay, and Novartis.

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

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

LAS VEGAS – With the right regimen, a majority of patients with psoriasis can achieve at least a Psoriasis Area and Severity Index (PASI) 75 score, Jennifer Soung, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

The array of treatment options includes mainstay topicals, new nonsteroidals, traditional oral systemics, new oral systemics, biologics, and light therapy, said Dr. Soung, director of clinical research at Harbor-UCLA Medical Center, Santa Ana, Calif. However, some areas of the body require unique considerations for successful psoriasis treatment, notably the scalp, face, intertriginous areas, palms and soles, and nails, she said.

For these areas, make sure the diagnosis of psoriasis is correct, to avoid wasting time on the wrong course of treatment, Dr. Soung emphasized.

Scalp strategies

The scalp is often the first area of the body affected by psoriasis, and patients with severe scalp psoriasis may have minimal plaques on the body, Dr. Soung said. However, a differential diagnosis should include seborrheic dermatitis, she noted.

For most cases of scalp psoriasis, “start with localized topical treatment,” such as vitamin D and corticosteroid combination therapy, or excimer laser, Dr. Soung advised.

Systemic treatments with demonstrated effectiveness on scalp psoriasis in post hoc analyses of patients with moderate to severe plaque psoriasis include adalimumab, etanercept, ixekizumab, and secukinumab. Studies specifically focused on treatment of scalp psoriasis have shown success with secukinumab and apremilast, she noted.

Roflumilast foam, 0.3%, is in development and is an emerging option for scalp psoriasis. (A cream formulation of roflumilast, a topical phosphodiesterase 4 inhibitor, was approved for treatment of plaque psoriasis in July 2022.) A phase 2b study of roflumilast foam showed that approximately one-third of patients with scalp psoriasis achieved a status of clear based on scalp-investigator global assessment, compared with approximately 3% of those on vehicle, and similar results were seen in a recently completed phase 3 trial for scalp and body psoriasis, she added.
 

Facial psoriasis

Patients with facial psoriasis tend to be younger, and they may have more severe disease overall, Dr. Soung said. Given the sensitivity of facial skin, “it is nice to have a nonsteroidal option,” she noted. Current novel nonsteroidal therapies include a cream formulation of tapinarof, an aryl hydrocarbon receptor agonist, which was approved earlier this year for plaque psoriasis in adults, and roflumilast cream. Vitamin D and topical calcineurin inhibitors are options as well, she said.

Intertriginous tricks

Intertriginous (inverse) psoriasis is distinct from other areas in that the plaques are usually smooth and well-demarcated, with little or no scaling, Dr. Soung said. Erosions or signs of maceration may be present. The prevalence of inverse psoriasis is approximately 30%, but the prevalence on external genitalia is 80%, she noted. For inverse psoriasis, topical corticosteroids can result in adverse events such as poor wound healing and skin fragility, and some patients resist the idea of a steroid and don’t adhere to the medication, she added. Dr. Soung recommended topical corticosteroids for the short term, and topical calcineurin inhibitors or calcipotriol for the long term.

New topical options for inverse psoriasis include tapinarof and roflumilast, Dr. Soung said. For tapinarof, the phase 3 PSOARING program included assessment of tolerability in sensitive skin areas and found little to no irritation. Similarly, treatment with roflumilast cream was effective and well tolerated by patients with intertriginous plaque psoriasis in the DERMIS-1 and DERMIS-2 studies, she said.
 

Genital psoriasis

Ask patients with psoriasis about genital psoriasis, because they often are too embarrassed to provide that information on their own, said Dr. Soung. In fact, 63% of patients with psoriasis report ever experiencing genital psoriasis, but it often goes undiagnosed and undertreated, which has a significant impact on patient quality of life and sexual health.

A differential diagnosis of genital psoriasis should include dermatitis, tinea or candidiasis, and even squamous cell carcinoma, she noted. Other considerations include fixed drug eruption, lichen nitidus, lichen sclerosus, and scabies.

Dr. Soung’s first line of treatment for genital psoriasis is low-potency topical corticosteroids for 2-4 weeks. If long-term topical therapy is needed, alternatives include calcineurin inhibitors and vitamin D analogs, she said. The new topicals roflumilast and tapinarof are options as well, she said.

For those patients with severe and extensive genital psoriasis, consider systemic therapy, possibly with ixekizumab or secukinumab, she added. Patients with moderate to severe genital psoriasis treated with apremilast have shown improvement at week 16, in an ongoing clinical trial, she noted.

Palmoplantar involvement

For patients with palmar plantar psoriasis, “don’t underestimate the impact on quality of life,” said Dr. Soung. Approximately 12%-16% of patients with psoriasis report palmoplantar involvement, she noted.

Palmoplantar psoriasis can be stubborn, and many patients will need combination therapy with topicals and systemics, she said. “I am very curious about how well our new topical nonsteroidals will work in these areas,” she added.

Dr. Soung starts patients with palmoplantar psoriasis with a “potent to super-potent” twice daily topical corticosteroid, with or without occlusion. Her first-line systemic therapy is acitretin, 10-50 mg daily. However, keep in mind that acitretin is contraindicated in pregnancy, and also may cause side effects including cheilitis, alopecia, and peeling skin, she cautioned.

During the question and answer session, Dr. Soung was asked whether she routinely biopsies patients with palmoplantar psoriasis. “Not always,” was her answer. Instead, she looks for clues elsewhere on the body to confirm the diagnosis.
 

Nail know-how

Approximately 23%-27% of patients with psoriasis experience nail involvement, said Dr. Soung. Nail psoriasis can appear on the nail plate as pitting, onycholysis, or subungual hyperkeratosis, or in the nail bed as splinter hemorrhages or oil spots, she said.

For patients with psoriasis of the nails only, Dr. Soung described the use of high-potency topical corticosteroids, with or without calcipotriol. In her experience, she said that intralesional steroids for nail psoriasis are torturous to patients. For patients who have failed topical therapy or have psoriasis in other areas, with or without psoriatic arthritis, she advised the use of either IL-17 antagonists (secukinumab, ixekizumab, brodalumab) or IL-23 antagonists (risankizumab, guselkumab).

Dr. Soung disclosed serving as a consultant or advisor for Arcutis, Bristol Myers Squibb Company, Dermavant, and Novartis. She also disclosed serving as a speaker or member of the speakers’ bureau for AbbVie, Amgen, Arcutis, Bristol Myers Squibb Company, Celgene, Leo Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and Sanofi, as well as research funding from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, KoBio, Kyowa Kirin, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

LAS VEGAS – With the right regimen, a majority of patients with psoriasis can achieve at least a Psoriasis Area and Severity Index (PASI) 75 score, Jennifer Soung, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

The array of treatment options includes mainstay topicals, new nonsteroidals, traditional oral systemics, new oral systemics, biologics, and light therapy, said Dr. Soung, director of clinical research at Harbor-UCLA Medical Center, Santa Ana, Calif. However, some areas of the body require unique considerations for successful psoriasis treatment, notably the scalp, face, intertriginous areas, palms and soles, and nails, she said.

For these areas, make sure the diagnosis of psoriasis is correct, to avoid wasting time on the wrong course of treatment, Dr. Soung emphasized.

Scalp strategies

The scalp is often the first area of the body affected by psoriasis, and patients with severe scalp psoriasis may have minimal plaques on the body, Dr. Soung said. However, a differential diagnosis should include seborrheic dermatitis, she noted.

For most cases of scalp psoriasis, “start with localized topical treatment,” such as vitamin D and corticosteroid combination therapy, or excimer laser, Dr. Soung advised.

Systemic treatments with demonstrated effectiveness on scalp psoriasis in post hoc analyses of patients with moderate to severe plaque psoriasis include adalimumab, etanercept, ixekizumab, and secukinumab. Studies specifically focused on treatment of scalp psoriasis have shown success with secukinumab and apremilast, she noted.

Roflumilast foam, 0.3%, is in development and is an emerging option for scalp psoriasis. (A cream formulation of roflumilast, a topical phosphodiesterase 4 inhibitor, was approved for treatment of plaque psoriasis in July 2022.) A phase 2b study of roflumilast foam showed that approximately one-third of patients with scalp psoriasis achieved a status of clear based on scalp-investigator global assessment, compared with approximately 3% of those on vehicle, and similar results were seen in a recently completed phase 3 trial for scalp and body psoriasis, she added.
 

Facial psoriasis

Patients with facial psoriasis tend to be younger, and they may have more severe disease overall, Dr. Soung said. Given the sensitivity of facial skin, “it is nice to have a nonsteroidal option,” she noted. Current novel nonsteroidal therapies include a cream formulation of tapinarof, an aryl hydrocarbon receptor agonist, which was approved earlier this year for plaque psoriasis in adults, and roflumilast cream. Vitamin D and topical calcineurin inhibitors are options as well, she said.

Intertriginous tricks

Intertriginous (inverse) psoriasis is distinct from other areas in that the plaques are usually smooth and well-demarcated, with little or no scaling, Dr. Soung said. Erosions or signs of maceration may be present. The prevalence of inverse psoriasis is approximately 30%, but the prevalence on external genitalia is 80%, she noted. For inverse psoriasis, topical corticosteroids can result in adverse events such as poor wound healing and skin fragility, and some patients resist the idea of a steroid and don’t adhere to the medication, she added. Dr. Soung recommended topical corticosteroids for the short term, and topical calcineurin inhibitors or calcipotriol for the long term.

New topical options for inverse psoriasis include tapinarof and roflumilast, Dr. Soung said. For tapinarof, the phase 3 PSOARING program included assessment of tolerability in sensitive skin areas and found little to no irritation. Similarly, treatment with roflumilast cream was effective and well tolerated by patients with intertriginous plaque psoriasis in the DERMIS-1 and DERMIS-2 studies, she said.
 

Genital psoriasis

Ask patients with psoriasis about genital psoriasis, because they often are too embarrassed to provide that information on their own, said Dr. Soung. In fact, 63% of patients with psoriasis report ever experiencing genital psoriasis, but it often goes undiagnosed and undertreated, which has a significant impact on patient quality of life and sexual health.

A differential diagnosis of genital psoriasis should include dermatitis, tinea or candidiasis, and even squamous cell carcinoma, she noted. Other considerations include fixed drug eruption, lichen nitidus, lichen sclerosus, and scabies.

Dr. Soung’s first line of treatment for genital psoriasis is low-potency topical corticosteroids for 2-4 weeks. If long-term topical therapy is needed, alternatives include calcineurin inhibitors and vitamin D analogs, she said. The new topicals roflumilast and tapinarof are options as well, she said.

For those patients with severe and extensive genital psoriasis, consider systemic therapy, possibly with ixekizumab or secukinumab, she added. Patients with moderate to severe genital psoriasis treated with apremilast have shown improvement at week 16, in an ongoing clinical trial, she noted.

Palmoplantar involvement

For patients with palmar plantar psoriasis, “don’t underestimate the impact on quality of life,” said Dr. Soung. Approximately 12%-16% of patients with psoriasis report palmoplantar involvement, she noted.

Palmoplantar psoriasis can be stubborn, and many patients will need combination therapy with topicals and systemics, she said. “I am very curious about how well our new topical nonsteroidals will work in these areas,” she added.

Dr. Soung starts patients with palmoplantar psoriasis with a “potent to super-potent” twice daily topical corticosteroid, with or without occlusion. Her first-line systemic therapy is acitretin, 10-50 mg daily. However, keep in mind that acitretin is contraindicated in pregnancy, and also may cause side effects including cheilitis, alopecia, and peeling skin, she cautioned.

During the question and answer session, Dr. Soung was asked whether she routinely biopsies patients with palmoplantar psoriasis. “Not always,” was her answer. Instead, she looks for clues elsewhere on the body to confirm the diagnosis.
 

Nail know-how

Approximately 23%-27% of patients with psoriasis experience nail involvement, said Dr. Soung. Nail psoriasis can appear on the nail plate as pitting, onycholysis, or subungual hyperkeratosis, or in the nail bed as splinter hemorrhages or oil spots, she said.

For patients with psoriasis of the nails only, Dr. Soung described the use of high-potency topical corticosteroids, with or without calcipotriol. In her experience, she said that intralesional steroids for nail psoriasis are torturous to patients. For patients who have failed topical therapy or have psoriasis in other areas, with or without psoriatic arthritis, she advised the use of either IL-17 antagonists (secukinumab, ixekizumab, brodalumab) or IL-23 antagonists (risankizumab, guselkumab).

Dr. Soung disclosed serving as a consultant or advisor for Arcutis, Bristol Myers Squibb Company, Dermavant, and Novartis. She also disclosed serving as a speaker or member of the speakers’ bureau for AbbVie, Amgen, Arcutis, Bristol Myers Squibb Company, Celgene, Leo Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and Sanofi, as well as research funding from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, KoBio, Kyowa Kirin, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

LAS VEGAS – With the right regimen, a majority of patients with psoriasis can achieve at least a Psoriasis Area and Severity Index (PASI) 75 score, Jennifer Soung, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

The array of treatment options includes mainstay topicals, new nonsteroidals, traditional oral systemics, new oral systemics, biologics, and light therapy, said Dr. Soung, director of clinical research at Harbor-UCLA Medical Center, Santa Ana, Calif. However, some areas of the body require unique considerations for successful psoriasis treatment, notably the scalp, face, intertriginous areas, palms and soles, and nails, she said.

For these areas, make sure the diagnosis of psoriasis is correct, to avoid wasting time on the wrong course of treatment, Dr. Soung emphasized.

Scalp strategies

The scalp is often the first area of the body affected by psoriasis, and patients with severe scalp psoriasis may have minimal plaques on the body, Dr. Soung said. However, a differential diagnosis should include seborrheic dermatitis, she noted.

For most cases of scalp psoriasis, “start with localized topical treatment,” such as vitamin D and corticosteroid combination therapy, or excimer laser, Dr. Soung advised.

Systemic treatments with demonstrated effectiveness on scalp psoriasis in post hoc analyses of patients with moderate to severe plaque psoriasis include adalimumab, etanercept, ixekizumab, and secukinumab. Studies specifically focused on treatment of scalp psoriasis have shown success with secukinumab and apremilast, she noted.

Roflumilast foam, 0.3%, is in development and is an emerging option for scalp psoriasis. (A cream formulation of roflumilast, a topical phosphodiesterase 4 inhibitor, was approved for treatment of plaque psoriasis in July 2022.) A phase 2b study of roflumilast foam showed that approximately one-third of patients with scalp psoriasis achieved a status of clear based on scalp-investigator global assessment, compared with approximately 3% of those on vehicle, and similar results were seen in a recently completed phase 3 trial for scalp and body psoriasis, she added.
 

Facial psoriasis

Patients with facial psoriasis tend to be younger, and they may have more severe disease overall, Dr. Soung said. Given the sensitivity of facial skin, “it is nice to have a nonsteroidal option,” she noted. Current novel nonsteroidal therapies include a cream formulation of tapinarof, an aryl hydrocarbon receptor agonist, which was approved earlier this year for plaque psoriasis in adults, and roflumilast cream. Vitamin D and topical calcineurin inhibitors are options as well, she said.

Intertriginous tricks

Intertriginous (inverse) psoriasis is distinct from other areas in that the plaques are usually smooth and well-demarcated, with little or no scaling, Dr. Soung said. Erosions or signs of maceration may be present. The prevalence of inverse psoriasis is approximately 30%, but the prevalence on external genitalia is 80%, she noted. For inverse psoriasis, topical corticosteroids can result in adverse events such as poor wound healing and skin fragility, and some patients resist the idea of a steroid and don’t adhere to the medication, she added. Dr. Soung recommended topical corticosteroids for the short term, and topical calcineurin inhibitors or calcipotriol for the long term.

New topical options for inverse psoriasis include tapinarof and roflumilast, Dr. Soung said. For tapinarof, the phase 3 PSOARING program included assessment of tolerability in sensitive skin areas and found little to no irritation. Similarly, treatment with roflumilast cream was effective and well tolerated by patients with intertriginous plaque psoriasis in the DERMIS-1 and DERMIS-2 studies, she said.
 

Genital psoriasis

Ask patients with psoriasis about genital psoriasis, because they often are too embarrassed to provide that information on their own, said Dr. Soung. In fact, 63% of patients with psoriasis report ever experiencing genital psoriasis, but it often goes undiagnosed and undertreated, which has a significant impact on patient quality of life and sexual health.

A differential diagnosis of genital psoriasis should include dermatitis, tinea or candidiasis, and even squamous cell carcinoma, she noted. Other considerations include fixed drug eruption, lichen nitidus, lichen sclerosus, and scabies.

Dr. Soung’s first line of treatment for genital psoriasis is low-potency topical corticosteroids for 2-4 weeks. If long-term topical therapy is needed, alternatives include calcineurin inhibitors and vitamin D analogs, she said. The new topicals roflumilast and tapinarof are options as well, she said.

For those patients with severe and extensive genital psoriasis, consider systemic therapy, possibly with ixekizumab or secukinumab, she added. Patients with moderate to severe genital psoriasis treated with apremilast have shown improvement at week 16, in an ongoing clinical trial, she noted.

Palmoplantar involvement

For patients with palmar plantar psoriasis, “don’t underestimate the impact on quality of life,” said Dr. Soung. Approximately 12%-16% of patients with psoriasis report palmoplantar involvement, she noted.

Palmoplantar psoriasis can be stubborn, and many patients will need combination therapy with topicals and systemics, she said. “I am very curious about how well our new topical nonsteroidals will work in these areas,” she added.

Dr. Soung starts patients with palmoplantar psoriasis with a “potent to super-potent” twice daily topical corticosteroid, with or without occlusion. Her first-line systemic therapy is acitretin, 10-50 mg daily. However, keep in mind that acitretin is contraindicated in pregnancy, and also may cause side effects including cheilitis, alopecia, and peeling skin, she cautioned.

During the question and answer session, Dr. Soung was asked whether she routinely biopsies patients with palmoplantar psoriasis. “Not always,” was her answer. Instead, she looks for clues elsewhere on the body to confirm the diagnosis.
 

Nail know-how

Approximately 23%-27% of patients with psoriasis experience nail involvement, said Dr. Soung. Nail psoriasis can appear on the nail plate as pitting, onycholysis, or subungual hyperkeratosis, or in the nail bed as splinter hemorrhages or oil spots, she said.

For patients with psoriasis of the nails only, Dr. Soung described the use of high-potency topical corticosteroids, with or without calcipotriol. In her experience, she said that intralesional steroids for nail psoriasis are torturous to patients. For patients who have failed topical therapy or have psoriasis in other areas, with or without psoriatic arthritis, she advised the use of either IL-17 antagonists (secukinumab, ixekizumab, brodalumab) or IL-23 antagonists (risankizumab, guselkumab).

Dr. Soung disclosed serving as a consultant or advisor for Arcutis, Bristol Myers Squibb Company, Dermavant, and Novartis. She also disclosed serving as a speaker or member of the speakers’ bureau for AbbVie, Amgen, Arcutis, Bristol Myers Squibb Company, Celgene, Leo Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and Sanofi, as well as research funding from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, KoBio, Kyowa Kirin, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

While nearly a quarter of patients with schizophrenia are reported to have primary treatment resistance, clozapine, known as the most effective antipsychotic for treatment-resistant schizophrenia – but burdened by concerns of side effects – remains significantly underprescribed, and when it is used, the drug is often delayed by several crucial years, reducing chances of efficacy.

“Despite being the only pharmacological therapy approved for treatment-resistant schizophrenia, clozapine is underutilized globally, even in developed countries, where only about 30% of patients who would benefit from the drug receive it,” said John M. Kane, MD, of the department of psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., in a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists in Cincinnati, Ohio.

Clozapine, a tricyclic dibenzodiazepine available in branded and various generic versions, is approved by the U.S. Food and Drug Administration as a third-line therapy for severe, treatment-resistant schizophrenia, with studies showing benefits exceeding those of any other antipsychotics for the indication.

But while recommendations suggest use after a trial of two or more antipsychotics, with at least one being an atypical antipsychotic, one recent review finds delays in clozapine commencement ranging from 19.3 weeks to 5.5 years, and the duration of illness prior to clozapine use ranging from 1.1 to 9.7 years.
 

Blood monitoring, side effects

The key deterrents preventing many clinicians and patients from trying clozapine sooner are the drug’s safety and tolerability profiles, and notably the requirement of regular blood testing due to an increased risk of agranulocytosis.

Specifically, the blood testing is required every week for 6 months, then every other week for the next 6 months, and then once a month after that; however, “many of us think that that’s excessive at this point in time,” Dr. Kane noted.

Various other potential side effects are also of concern, including myocarditis, seizures, constipation, arrhythmia, hypersalivation, pneumonia, and metabolic symptoms including diabetes.

In terms of the common strategies that clinicians turn to when patients fail to respond to their current antipsychotic, including increasing doses, combining agents, or treatment switching, “none of the strategies likely rival clozapine in terms of efficacy,” Dr. Kane said.

Regarding higher dosing: “There is very little data suggesting that higher doses of antipsychotic drugs will work when the moderate or recommended dose has not worked,” he said.

Combination therapy strategies may provide benefits, but “they’re not a substitute for clozapine,” Dr. Kane added, noting that the combinations that do appear to be the most effective involve clozapine.

And regarding drug switching, studies suggest the likelihood of response in switching from one drug to another is “actually very low,” Dr. Kane added.

Clozapine also doesn’t work for all – the response rate runs between about 30% and 60%, Dr. Kane said, but when it is effective, the benefits can be profound.

“There are some patients who have a very pronounced response to clozapine – some patients describe it as life-changing,” he said.
 

Treatment delays reduce efficacy

Importantly, the delays before receiving clozapine are not inconsequential – data show that each outpatient antipsychotic trial prior to clozapine reduces the likelihood of response by 8%-11%, and each hospital admission further reduces the likelihood of response by 4%-8%, underscoring the need to identify treatment resistance as early as possible, Dr. Kane said.

“It’s critically important to try to identify treatment resistance earlier than we usually do because if we can get it under control sooner, we have a better chance of improving the patient’s outcome, and this has been shown in a number of studies,” he said.

“The longer you wait, the less likely you are to see a good response even to clozapine.”

Despite the concerns about clozapine, Dr. Kane notes that even the blood monitoring does not appear to be a big complaint for patients, especially they are improving.

“In our experience, the patients who benefit from clozapine don’t really have a problem with the monitoring,” he said.

“In fact, patients who benefit from clozapine are much more adherent to the medication than other patients that we see, which is understandable, because if you feel you’re really getting a benefit from medicine, you’re going to be much more motivated to take it even if it has side effects.”

A recent systematic review of 13 studies and 1,487 patients backs that up, concluding that “patients generally have a favorable experience when being treated with clozapine,” with the caveat that “conclusions are limited by the risk of bias, particularly survivorship bias.”

Preference for clozapine over other antipsychotic medications was reported by 54%-86% of patients in the review, with specific improvements in mood (11%-78%) and cognition (5%-68%).
 

Clinicians the biggest ‘obstacle’

Dr. Kane notes that an important factor in underutilization could indeed be the manner in which clinicians discuss clozapine with their patients – often opening the discussion by focusing on the negative aspects that, without the context of the potential benefits, can be deal-breakers for patient from the start.

“The clinicians in my opinion are really the obstacle,” Dr. Kane said. “What we always hear from clinicians is ‘I can’t do it because the patient refuses, or the patient doesn’t like the side effects’.”

Dr. Kane notes that most side effects can indeed be managed – regarding the risk for metabolic syndrome, for instance, he recommends that patients should be given metformin from the beginning when they’re started on clozapine.

He adds that in most cases, a 3-month trial is enough to answer the question of whether clozapine is working or not.

“Three months is a good trial, but it may not even tell you the total response to clozapine because that may actually accrue over time,” he said. “We’ve seen patients who actually get better and better beyond 3 months.”

Not offering the drug to patients, however, is doing them a serious disservice, Dr. Kane added.

“What I tell patients and families is that it would be a shame to miss this opportunity for a potential treatment that could be life-changing,” he said. “Does it have potential side effects? Yes. Do you have to get blood tests? Yes. And I can’t tell by evaluating a patient’s history or examining that patient whether or not they’re going to be a good responder. But would you really want to miss an opportunity to find that out?”

“To me the argument is – let’s try this drug for 3 months and see what effect it has, and at that point you’ll be in a much better position to make a decision about the benefits versus risk,” Dr. Kane said.
 

The only FDA-approved drug for treatment-resistant schizophrenia

Remarkably, clozapine isn’t just the only drug to currently have approval from the FDA for treatment-resistant schizophrenia – it has been for the last 3 decades.

“There have been attempts to develop medications with similar efficacy, but they have not succeeded,” Dr. Kane said in an interview. “We are still uncertain as to what accounts for clozapine’s unique qualities.”

Yet, with treatment-resistant schizophrenia patients representing some of the most dire mental illness cases clinicians may face, the need for better treatment decisions – and additional options – is pressing, Dr. Kane said.

“[The lack of any other drugs] is a big embarrassment to our field, in my opinion,” he said. “I’m a big proponent of clozapine, but we should have found another substance by now that could substitute for clozapine, which obviously has a lot of side effects and is not the easiest drug to use.”

Dr. Kane reported relationships either as a speaker or consultant/advisory board member and/or receives research grant support from Alkermes, Allergan, Click Therapeutics, Dainippon Sumitomo, H. Lundbeck, HLS Therapeutics, Indivior, Intra-Cellular Therapies, Janssen Pharmaceutical, Johnson & Johnson, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Neumora Therapeutics, Novartis Pharmaceuticals, Otsuka, Reviva, Roche, Saladax, Sunovion, Takeda, and Teva. Dr. Kane receives non-mutual funds stock ownership/stock options from LB Pharmaceuticals, Vanguard Research Group, and North Shore Therapeutics, and receives patent holder/royalties paid by UpToDate.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

While nearly a quarter of patients with schizophrenia are reported to have primary treatment resistance, clozapine, known as the most effective antipsychotic for treatment-resistant schizophrenia – but burdened by concerns of side effects – remains significantly underprescribed, and when it is used, the drug is often delayed by several crucial years, reducing chances of efficacy.

“Despite being the only pharmacological therapy approved for treatment-resistant schizophrenia, clozapine is underutilized globally, even in developed countries, where only about 30% of patients who would benefit from the drug receive it,” said John M. Kane, MD, of the department of psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., in a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists in Cincinnati, Ohio.

Clozapine, a tricyclic dibenzodiazepine available in branded and various generic versions, is approved by the U.S. Food and Drug Administration as a third-line therapy for severe, treatment-resistant schizophrenia, with studies showing benefits exceeding those of any other antipsychotics for the indication.

But while recommendations suggest use after a trial of two or more antipsychotics, with at least one being an atypical antipsychotic, one recent review finds delays in clozapine commencement ranging from 19.3 weeks to 5.5 years, and the duration of illness prior to clozapine use ranging from 1.1 to 9.7 years.
 

Blood monitoring, side effects

The key deterrents preventing many clinicians and patients from trying clozapine sooner are the drug’s safety and tolerability profiles, and notably the requirement of regular blood testing due to an increased risk of agranulocytosis.

Specifically, the blood testing is required every week for 6 months, then every other week for the next 6 months, and then once a month after that; however, “many of us think that that’s excessive at this point in time,” Dr. Kane noted.

Various other potential side effects are also of concern, including myocarditis, seizures, constipation, arrhythmia, hypersalivation, pneumonia, and metabolic symptoms including diabetes.

In terms of the common strategies that clinicians turn to when patients fail to respond to their current antipsychotic, including increasing doses, combining agents, or treatment switching, “none of the strategies likely rival clozapine in terms of efficacy,” Dr. Kane said.

Regarding higher dosing: “There is very little data suggesting that higher doses of antipsychotic drugs will work when the moderate or recommended dose has not worked,” he said.

Combination therapy strategies may provide benefits, but “they’re not a substitute for clozapine,” Dr. Kane added, noting that the combinations that do appear to be the most effective involve clozapine.

And regarding drug switching, studies suggest the likelihood of response in switching from one drug to another is “actually very low,” Dr. Kane added.

Clozapine also doesn’t work for all – the response rate runs between about 30% and 60%, Dr. Kane said, but when it is effective, the benefits can be profound.

“There are some patients who have a very pronounced response to clozapine – some patients describe it as life-changing,” he said.
 

Treatment delays reduce efficacy

Importantly, the delays before receiving clozapine are not inconsequential – data show that each outpatient antipsychotic trial prior to clozapine reduces the likelihood of response by 8%-11%, and each hospital admission further reduces the likelihood of response by 4%-8%, underscoring the need to identify treatment resistance as early as possible, Dr. Kane said.

“It’s critically important to try to identify treatment resistance earlier than we usually do because if we can get it under control sooner, we have a better chance of improving the patient’s outcome, and this has been shown in a number of studies,” he said.

“The longer you wait, the less likely you are to see a good response even to clozapine.”

Despite the concerns about clozapine, Dr. Kane notes that even the blood monitoring does not appear to be a big complaint for patients, especially they are improving.

“In our experience, the patients who benefit from clozapine don’t really have a problem with the monitoring,” he said.

“In fact, patients who benefit from clozapine are much more adherent to the medication than other patients that we see, which is understandable, because if you feel you’re really getting a benefit from medicine, you’re going to be much more motivated to take it even if it has side effects.”

A recent systematic review of 13 studies and 1,487 patients backs that up, concluding that “patients generally have a favorable experience when being treated with clozapine,” with the caveat that “conclusions are limited by the risk of bias, particularly survivorship bias.”

Preference for clozapine over other antipsychotic medications was reported by 54%-86% of patients in the review, with specific improvements in mood (11%-78%) and cognition (5%-68%).
 

Clinicians the biggest ‘obstacle’

Dr. Kane notes that an important factor in underutilization could indeed be the manner in which clinicians discuss clozapine with their patients – often opening the discussion by focusing on the negative aspects that, without the context of the potential benefits, can be deal-breakers for patient from the start.

“The clinicians in my opinion are really the obstacle,” Dr. Kane said. “What we always hear from clinicians is ‘I can’t do it because the patient refuses, or the patient doesn’t like the side effects’.”

Dr. Kane notes that most side effects can indeed be managed – regarding the risk for metabolic syndrome, for instance, he recommends that patients should be given metformin from the beginning when they’re started on clozapine.

He adds that in most cases, a 3-month trial is enough to answer the question of whether clozapine is working or not.

“Three months is a good trial, but it may not even tell you the total response to clozapine because that may actually accrue over time,” he said. “We’ve seen patients who actually get better and better beyond 3 months.”

Not offering the drug to patients, however, is doing them a serious disservice, Dr. Kane added.

“What I tell patients and families is that it would be a shame to miss this opportunity for a potential treatment that could be life-changing,” he said. “Does it have potential side effects? Yes. Do you have to get blood tests? Yes. And I can’t tell by evaluating a patient’s history or examining that patient whether or not they’re going to be a good responder. But would you really want to miss an opportunity to find that out?”

“To me the argument is – let’s try this drug for 3 months and see what effect it has, and at that point you’ll be in a much better position to make a decision about the benefits versus risk,” Dr. Kane said.
 

The only FDA-approved drug for treatment-resistant schizophrenia

Remarkably, clozapine isn’t just the only drug to currently have approval from the FDA for treatment-resistant schizophrenia – it has been for the last 3 decades.

“There have been attempts to develop medications with similar efficacy, but they have not succeeded,” Dr. Kane said in an interview. “We are still uncertain as to what accounts for clozapine’s unique qualities.”

Yet, with treatment-resistant schizophrenia patients representing some of the most dire mental illness cases clinicians may face, the need for better treatment decisions – and additional options – is pressing, Dr. Kane said.

“[The lack of any other drugs] is a big embarrassment to our field, in my opinion,” he said. “I’m a big proponent of clozapine, but we should have found another substance by now that could substitute for clozapine, which obviously has a lot of side effects and is not the easiest drug to use.”

Dr. Kane reported relationships either as a speaker or consultant/advisory board member and/or receives research grant support from Alkermes, Allergan, Click Therapeutics, Dainippon Sumitomo, H. Lundbeck, HLS Therapeutics, Indivior, Intra-Cellular Therapies, Janssen Pharmaceutical, Johnson & Johnson, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Neumora Therapeutics, Novartis Pharmaceuticals, Otsuka, Reviva, Roche, Saladax, Sunovion, Takeda, and Teva. Dr. Kane receives non-mutual funds stock ownership/stock options from LB Pharmaceuticals, Vanguard Research Group, and North Shore Therapeutics, and receives patent holder/royalties paid by UpToDate.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

While nearly a quarter of patients with schizophrenia are reported to have primary treatment resistance, clozapine, known as the most effective antipsychotic for treatment-resistant schizophrenia – but burdened by concerns of side effects – remains significantly underprescribed, and when it is used, the drug is often delayed by several crucial years, reducing chances of efficacy.

“Despite being the only pharmacological therapy approved for treatment-resistant schizophrenia, clozapine is underutilized globally, even in developed countries, where only about 30% of patients who would benefit from the drug receive it,” said John M. Kane, MD, of the department of psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y., in a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists in Cincinnati, Ohio.

Clozapine, a tricyclic dibenzodiazepine available in branded and various generic versions, is approved by the U.S. Food and Drug Administration as a third-line therapy for severe, treatment-resistant schizophrenia, with studies showing benefits exceeding those of any other antipsychotics for the indication.

But while recommendations suggest use after a trial of two or more antipsychotics, with at least one being an atypical antipsychotic, one recent review finds delays in clozapine commencement ranging from 19.3 weeks to 5.5 years, and the duration of illness prior to clozapine use ranging from 1.1 to 9.7 years.
 

Blood monitoring, side effects

The key deterrents preventing many clinicians and patients from trying clozapine sooner are the drug’s safety and tolerability profiles, and notably the requirement of regular blood testing due to an increased risk of agranulocytosis.

Specifically, the blood testing is required every week for 6 months, then every other week for the next 6 months, and then once a month after that; however, “many of us think that that’s excessive at this point in time,” Dr. Kane noted.

Various other potential side effects are also of concern, including myocarditis, seizures, constipation, arrhythmia, hypersalivation, pneumonia, and metabolic symptoms including diabetes.

In terms of the common strategies that clinicians turn to when patients fail to respond to their current antipsychotic, including increasing doses, combining agents, or treatment switching, “none of the strategies likely rival clozapine in terms of efficacy,” Dr. Kane said.

Regarding higher dosing: “There is very little data suggesting that higher doses of antipsychotic drugs will work when the moderate or recommended dose has not worked,” he said.

Combination therapy strategies may provide benefits, but “they’re not a substitute for clozapine,” Dr. Kane added, noting that the combinations that do appear to be the most effective involve clozapine.

And regarding drug switching, studies suggest the likelihood of response in switching from one drug to another is “actually very low,” Dr. Kane added.

Clozapine also doesn’t work for all – the response rate runs between about 30% and 60%, Dr. Kane said, but when it is effective, the benefits can be profound.

“There are some patients who have a very pronounced response to clozapine – some patients describe it as life-changing,” he said.
 

Treatment delays reduce efficacy

Importantly, the delays before receiving clozapine are not inconsequential – data show that each outpatient antipsychotic trial prior to clozapine reduces the likelihood of response by 8%-11%, and each hospital admission further reduces the likelihood of response by 4%-8%, underscoring the need to identify treatment resistance as early as possible, Dr. Kane said.

“It’s critically important to try to identify treatment resistance earlier than we usually do because if we can get it under control sooner, we have a better chance of improving the patient’s outcome, and this has been shown in a number of studies,” he said.

“The longer you wait, the less likely you are to see a good response even to clozapine.”

Despite the concerns about clozapine, Dr. Kane notes that even the blood monitoring does not appear to be a big complaint for patients, especially they are improving.

“In our experience, the patients who benefit from clozapine don’t really have a problem with the monitoring,” he said.

“In fact, patients who benefit from clozapine are much more adherent to the medication than other patients that we see, which is understandable, because if you feel you’re really getting a benefit from medicine, you’re going to be much more motivated to take it even if it has side effects.”

A recent systematic review of 13 studies and 1,487 patients backs that up, concluding that “patients generally have a favorable experience when being treated with clozapine,” with the caveat that “conclusions are limited by the risk of bias, particularly survivorship bias.”

Preference for clozapine over other antipsychotic medications was reported by 54%-86% of patients in the review, with specific improvements in mood (11%-78%) and cognition (5%-68%).
 

Clinicians the biggest ‘obstacle’

Dr. Kane notes that an important factor in underutilization could indeed be the manner in which clinicians discuss clozapine with their patients – often opening the discussion by focusing on the negative aspects that, without the context of the potential benefits, can be deal-breakers for patient from the start.

“The clinicians in my opinion are really the obstacle,” Dr. Kane said. “What we always hear from clinicians is ‘I can’t do it because the patient refuses, or the patient doesn’t like the side effects’.”

Dr. Kane notes that most side effects can indeed be managed – regarding the risk for metabolic syndrome, for instance, he recommends that patients should be given metformin from the beginning when they’re started on clozapine.

He adds that in most cases, a 3-month trial is enough to answer the question of whether clozapine is working or not.

“Three months is a good trial, but it may not even tell you the total response to clozapine because that may actually accrue over time,” he said. “We’ve seen patients who actually get better and better beyond 3 months.”

Not offering the drug to patients, however, is doing them a serious disservice, Dr. Kane added.

“What I tell patients and families is that it would be a shame to miss this opportunity for a potential treatment that could be life-changing,” he said. “Does it have potential side effects? Yes. Do you have to get blood tests? Yes. And I can’t tell by evaluating a patient’s history or examining that patient whether or not they’re going to be a good responder. But would you really want to miss an opportunity to find that out?”

“To me the argument is – let’s try this drug for 3 months and see what effect it has, and at that point you’ll be in a much better position to make a decision about the benefits versus risk,” Dr. Kane said.
 

The only FDA-approved drug for treatment-resistant schizophrenia

Remarkably, clozapine isn’t just the only drug to currently have approval from the FDA for treatment-resistant schizophrenia – it has been for the last 3 decades.

“There have been attempts to develop medications with similar efficacy, but they have not succeeded,” Dr. Kane said in an interview. “We are still uncertain as to what accounts for clozapine’s unique qualities.”

Yet, with treatment-resistant schizophrenia patients representing some of the most dire mental illness cases clinicians may face, the need for better treatment decisions – and additional options – is pressing, Dr. Kane said.

“[The lack of any other drugs] is a big embarrassment to our field, in my opinion,” he said. “I’m a big proponent of clozapine, but we should have found another substance by now that could substitute for clozapine, which obviously has a lot of side effects and is not the easiest drug to use.”

Dr. Kane reported relationships either as a speaker or consultant/advisory board member and/or receives research grant support from Alkermes, Allergan, Click Therapeutics, Dainippon Sumitomo, H. Lundbeck, HLS Therapeutics, Indivior, Intra-Cellular Therapies, Janssen Pharmaceutical, Johnson & Johnson, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Neumora Therapeutics, Novartis Pharmaceuticals, Otsuka, Reviva, Roche, Saladax, Sunovion, Takeda, and Teva. Dr. Kane receives non-mutual funds stock ownership/stock options from LB Pharmaceuticals, Vanguard Research Group, and North Shore Therapeutics, and receives patent holder/royalties paid by UpToDate.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

CHICAGO – A clinical decision-support tool designed to identify hospitalized patients who need thromboembolism prophylaxis and embedded in a hospital’s electronic health record led to significantly more appropriate prophylaxis, compared with usual care, and significantly cut the 30-day rate of thromboembolism in a randomized, multicenter trial with more than 10,000 patients.

“This is the first time that a clinical decision support tool not only changed [thromboprophylaxis prescribing] behavior but also affected hard outcomes. That’s remarkable,” lead investigator Alex C. Spyropoulos, MD, said in an interview.

Even so, outside experts expressed concerns about certain results and the trial design.

Mitchel L. Zoler/MDedge News

Use of the decision-support risk calculator for thromboembolism in the IMPROVE-DD VTE trial significantly boosted use of appropriate inpatient thromboprophylaxis starting at hospital admission by a relative 52%, and significantly increased outpatient thromboprophylaxis prescribed at discharge by a relative 93% in the study’s two primary endpoints, Dr. Spyropoulos reported at the American Heart Association scientific sessions.

This intervention led to a significant 29% relative reduction in the incidence of total thromboembolic events, both venous and arterial, during hospitalization and through 30 days post discharge.

The absolute thromboembolic event rates were 2.9% among 5,249 patients treated at either of two U.S. hospitals that used the EHR-based risk calculator and 4.0% in 5,450 patients seen at either of two other U.S. hospitals that served as controls and where usual care method identified patients who needed thromboprophylaxis, said Dr. Spyropoulos, professor and director of the anticoagulation and clinical thrombosis services for Northwell Health in New York. This included a 2.7% rate of venous thromboembolism and a 0.25% rate of arterial thromboembolism in the intervention patients, and a 3.3% rate of venous events and a 0.7% rate of arterial events in the controls.

Patients treated at the hospitals that used the EHR-embedded risk calculator also has a numerically lower rate of major bleeding events during hospitalization and 30-day postdischarge follow-up, a 0.15% rate compared with a 0.22% rate in the control patients, a difference that was not significant.
 

A ‘powerful message’

“It’s a powerful message to see an absolute 1.1% difference in the rate of thromboembolism and a trend to fewer major bleeds. I think this will change practice,” Dr. Spyropoulos added in the interview. “The next step is dissemination.”

But thromboprophylaxis experts cautioned that, while the results looked promising, the findings need more analysis and review, and the intervention may need further testing before it’s ready for widespread use.

For example, one unexpected result was an unexpected 2.1 percentage point increase in all-cause mortality linked with use of the decision-support tool. Total deaths from admission to 30 days after discharge occurred in 9.1% of the patients treated at the two hospitals that used the risk calculator and 7.0% among the control patients, a difference that Dr, Spyropoulos said was likely the result of unbalanced outcomes from COVID-19 infections that had no relevance to the tested intervention. The trial ran during December 2020–January 2022.
 

But wait – more detail and analysis needed

“I’d like to see more analysis of the data from this trial,” and “there is the issue of increased mortality,” commented Gregory Piazza, MD, director of vascular medicine at Brigham and Women’s Hospital in Boston, and a specialist in thromboembolism prevention and management. He also highlighted the need for greater detail on the arterial thromboembolic events tallied during the study.

With more details and analysis of these findings “we’ll learn more about the true impact” of this intervention, Dr. Piazza said in an interview.

Mitchel L. Zoler/MDedge News

“The increased mortality in the intervention group may have been due to differential treatment and decision-making and confounding and warrants further investigation,” commented Elaine M. Hylek, MD, a professor at Boston University and designated discussant for the report. Selection bias may have contributed to this possible confounding, Dr. Hylek noted.

Other limitations of the study cited by Dr. Hylek included its reliance on individual clinician decision-making to actually prescribe thromboprophylaxis, a lack of information on patient adherence to their thromboprophylaxis prescription, and an overall low rate of appropriate thromboprophylaxis prescribed to patients at discharge. The rates were 7.5% among the controls and 13.6% among patients in the intervention arm. For prescription at the time of hospitalization, the rates were 72.5% among control patients and 80.1% for patients seen at the two hospitals that used the decision-support tool.
 

The IMPROVE-DD VTE risk assessment tool

The clinical decision-support tool tested is called the IMPROVE-DD VTE risk assessment model, developed over several years by Dr. Spyropoulos and associates; they have also performed multiple validation studies. The model includes eight factors that score 1-3 points if positive that can add up to total scores of 0-14. A score of 0 or 1 is considered low risk, 2 or 3 intermediate risk, and 4 or more high risk. One of the scoring factors is the result of a D-dimer test, which explains the DD part of the name.

The eight factors and point assignments are prior venous thromboembolism: 3 points; known thrombophilia: 2 points; lower limb paralysis: 2 points; current cancer: 2 points; d-dimer level more than twofold the upper limit of normal: 2 points; immobilized for at least 7 days: 1 point; admitted to the ICU or coronary care unit: 1 point; and age greater than 60 years old: 1 point.

Development of the IMPROVE-DD VTE risk calculator received most of its funding from the U.S. Agency for Healthcare Research and Quality, and the risk tool will be available for hospitals and health systems to access at no charge through the agency’s website, Dr. Spyropoulos said. The researchers designed the calculator to operate in any EHR product.

IMPROVE-DD VTE “is a very valid, high-quality tool,” commented Dr. Piazza. “We’ve used some rather blunt tools in the past,” and especially praised inclusion of D-dimer results into the IMPROVE-DD VTE model.

“It’s nice to use a biomarker in addition to clinical factors,” he said. “A biomarker provides a more holistic picture; we can’t do genetic testing on every patient.”

Enrollment focused on higher-risk patients

The study ran at four academic, tertiary-care hospitals in the Northwell Health network in the New York region. It enrolled patients aged more than 60 years who were hospitalized for any of five diagnoses: heart failure; acute respiratory insufficiency, including chronic obstructive lung disease or asthma; acute infectious disease, including COVID-19; acute inflammatory disease, including rheumatic disease; or acute stroke. The study excluded patients with a history of atrial fibrillation, those who used an anticoagulant at home, or those who had received therapeutic anticoagulation within 24 hours of their hospital admission.

The anticoagulant prophylaxis that patients received depended on their calculated risk level – intermediate or high – and whether they were inpatients or being discharged. The anticoagulants that clinicians could prescribe included unfractionated heparin, enoxaparin, fondaparinux, rivaroxaban, and apixaban.

“We’ve been looking for a long time for a tool for medically ill patients that’s like the CHA2DS2-VASc score” for patients with atrial fibrillation. “These powerful data say we now have this, and the EHR provides a vehicle to easily implement it,” Dr. Spyropoulos said.

The IMPROVE-DD VTE study received partial funding from Janssen. Dr. Spyropoulos has been a consultant to Nayer, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Pfizer, and Sanofi; adviser to the ATLAS Group; and has received research support from Janssen. Dr. Piazza has received research funding from Bayer, BIG/EKOS, BMS, Janssen, and Portola. Dr. Hylek had been a consultant to Bayer and Ionis, and has received honoraria from Boehringer Ingelheim and Pfizer.

CHICAGO – A clinical decision-support tool designed to identify hospitalized patients who need thromboembolism prophylaxis and embedded in a hospital’s electronic health record led to significantly more appropriate prophylaxis, compared with usual care, and significantly cut the 30-day rate of thromboembolism in a randomized, multicenter trial with more than 10,000 patients.

“This is the first time that a clinical decision support tool not only changed [thromboprophylaxis prescribing] behavior but also affected hard outcomes. That’s remarkable,” lead investigator Alex C. Spyropoulos, MD, said in an interview.

Even so, outside experts expressed concerns about certain results and the trial design.

Mitchel L. Zoler/MDedge News

Use of the decision-support risk calculator for thromboembolism in the IMPROVE-DD VTE trial significantly boosted use of appropriate inpatient thromboprophylaxis starting at hospital admission by a relative 52%, and significantly increased outpatient thromboprophylaxis prescribed at discharge by a relative 93% in the study’s two primary endpoints, Dr. Spyropoulos reported at the American Heart Association scientific sessions.

This intervention led to a significant 29% relative reduction in the incidence of total thromboembolic events, both venous and arterial, during hospitalization and through 30 days post discharge.

The absolute thromboembolic event rates were 2.9% among 5,249 patients treated at either of two U.S. hospitals that used the EHR-based risk calculator and 4.0% in 5,450 patients seen at either of two other U.S. hospitals that served as controls and where usual care method identified patients who needed thromboprophylaxis, said Dr. Spyropoulos, professor and director of the anticoagulation and clinical thrombosis services for Northwell Health in New York. This included a 2.7% rate of venous thromboembolism and a 0.25% rate of arterial thromboembolism in the intervention patients, and a 3.3% rate of venous events and a 0.7% rate of arterial events in the controls.

Patients treated at the hospitals that used the EHR-embedded risk calculator also has a numerically lower rate of major bleeding events during hospitalization and 30-day postdischarge follow-up, a 0.15% rate compared with a 0.22% rate in the control patients, a difference that was not significant.
 

A ‘powerful message’

“It’s a powerful message to see an absolute 1.1% difference in the rate of thromboembolism and a trend to fewer major bleeds. I think this will change practice,” Dr. Spyropoulos added in the interview. “The next step is dissemination.”

But thromboprophylaxis experts cautioned that, while the results looked promising, the findings need more analysis and review, and the intervention may need further testing before it’s ready for widespread use.

For example, one unexpected result was an unexpected 2.1 percentage point increase in all-cause mortality linked with use of the decision-support tool. Total deaths from admission to 30 days after discharge occurred in 9.1% of the patients treated at the two hospitals that used the risk calculator and 7.0% among the control patients, a difference that Dr, Spyropoulos said was likely the result of unbalanced outcomes from COVID-19 infections that had no relevance to the tested intervention. The trial ran during December 2020–January 2022.
 

But wait – more detail and analysis needed

“I’d like to see more analysis of the data from this trial,” and “there is the issue of increased mortality,” commented Gregory Piazza, MD, director of vascular medicine at Brigham and Women’s Hospital in Boston, and a specialist in thromboembolism prevention and management. He also highlighted the need for greater detail on the arterial thromboembolic events tallied during the study.

With more details and analysis of these findings “we’ll learn more about the true impact” of this intervention, Dr. Piazza said in an interview.

Mitchel L. Zoler/MDedge News

“The increased mortality in the intervention group may have been due to differential treatment and decision-making and confounding and warrants further investigation,” commented Elaine M. Hylek, MD, a professor at Boston University and designated discussant for the report. Selection bias may have contributed to this possible confounding, Dr. Hylek noted.

Other limitations of the study cited by Dr. Hylek included its reliance on individual clinician decision-making to actually prescribe thromboprophylaxis, a lack of information on patient adherence to their thromboprophylaxis prescription, and an overall low rate of appropriate thromboprophylaxis prescribed to patients at discharge. The rates were 7.5% among the controls and 13.6% among patients in the intervention arm. For prescription at the time of hospitalization, the rates were 72.5% among control patients and 80.1% for patients seen at the two hospitals that used the decision-support tool.
 

The IMPROVE-DD VTE risk assessment tool

The clinical decision-support tool tested is called the IMPROVE-DD VTE risk assessment model, developed over several years by Dr. Spyropoulos and associates; they have also performed multiple validation studies. The model includes eight factors that score 1-3 points if positive that can add up to total scores of 0-14. A score of 0 or 1 is considered low risk, 2 or 3 intermediate risk, and 4 or more high risk. One of the scoring factors is the result of a D-dimer test, which explains the DD part of the name.

The eight factors and point assignments are prior venous thromboembolism: 3 points; known thrombophilia: 2 points; lower limb paralysis: 2 points; current cancer: 2 points; d-dimer level more than twofold the upper limit of normal: 2 points; immobilized for at least 7 days: 1 point; admitted to the ICU or coronary care unit: 1 point; and age greater than 60 years old: 1 point.

Development of the IMPROVE-DD VTE risk calculator received most of its funding from the U.S. Agency for Healthcare Research and Quality, and the risk tool will be available for hospitals and health systems to access at no charge through the agency’s website, Dr. Spyropoulos said. The researchers designed the calculator to operate in any EHR product.

IMPROVE-DD VTE “is a very valid, high-quality tool,” commented Dr. Piazza. “We’ve used some rather blunt tools in the past,” and especially praised inclusion of D-dimer results into the IMPROVE-DD VTE model.

“It’s nice to use a biomarker in addition to clinical factors,” he said. “A biomarker provides a more holistic picture; we can’t do genetic testing on every patient.”

Enrollment focused on higher-risk patients

The study ran at four academic, tertiary-care hospitals in the Northwell Health network in the New York region. It enrolled patients aged more than 60 years who were hospitalized for any of five diagnoses: heart failure; acute respiratory insufficiency, including chronic obstructive lung disease or asthma; acute infectious disease, including COVID-19; acute inflammatory disease, including rheumatic disease; or acute stroke. The study excluded patients with a history of atrial fibrillation, those who used an anticoagulant at home, or those who had received therapeutic anticoagulation within 24 hours of their hospital admission.

The anticoagulant prophylaxis that patients received depended on their calculated risk level – intermediate or high – and whether they were inpatients or being discharged. The anticoagulants that clinicians could prescribe included unfractionated heparin, enoxaparin, fondaparinux, rivaroxaban, and apixaban.

“We’ve been looking for a long time for a tool for medically ill patients that’s like the CHA2DS2-VASc score” for patients with atrial fibrillation. “These powerful data say we now have this, and the EHR provides a vehicle to easily implement it,” Dr. Spyropoulos said.

The IMPROVE-DD VTE study received partial funding from Janssen. Dr. Spyropoulos has been a consultant to Nayer, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Pfizer, and Sanofi; adviser to the ATLAS Group; and has received research support from Janssen. Dr. Piazza has received research funding from Bayer, BIG/EKOS, BMS, Janssen, and Portola. Dr. Hylek had been a consultant to Bayer and Ionis, and has received honoraria from Boehringer Ingelheim and Pfizer.

CHICAGO – A clinical decision-support tool designed to identify hospitalized patients who need thromboembolism prophylaxis and embedded in a hospital’s electronic health record led to significantly more appropriate prophylaxis, compared with usual care, and significantly cut the 30-day rate of thromboembolism in a randomized, multicenter trial with more than 10,000 patients.

“This is the first time that a clinical decision support tool not only changed [thromboprophylaxis prescribing] behavior but also affected hard outcomes. That’s remarkable,” lead investigator Alex C. Spyropoulos, MD, said in an interview.

Even so, outside experts expressed concerns about certain results and the trial design.

Mitchel L. Zoler/MDedge News

Use of the decision-support risk calculator for thromboembolism in the IMPROVE-DD VTE trial significantly boosted use of appropriate inpatient thromboprophylaxis starting at hospital admission by a relative 52%, and significantly increased outpatient thromboprophylaxis prescribed at discharge by a relative 93% in the study’s two primary endpoints, Dr. Spyropoulos reported at the American Heart Association scientific sessions.

This intervention led to a significant 29% relative reduction in the incidence of total thromboembolic events, both venous and arterial, during hospitalization and through 30 days post discharge.

The absolute thromboembolic event rates were 2.9% among 5,249 patients treated at either of two U.S. hospitals that used the EHR-based risk calculator and 4.0% in 5,450 patients seen at either of two other U.S. hospitals that served as controls and where usual care method identified patients who needed thromboprophylaxis, said Dr. Spyropoulos, professor and director of the anticoagulation and clinical thrombosis services for Northwell Health in New York. This included a 2.7% rate of venous thromboembolism and a 0.25% rate of arterial thromboembolism in the intervention patients, and a 3.3% rate of venous events and a 0.7% rate of arterial events in the controls.

Patients treated at the hospitals that used the EHR-embedded risk calculator also has a numerically lower rate of major bleeding events during hospitalization and 30-day postdischarge follow-up, a 0.15% rate compared with a 0.22% rate in the control patients, a difference that was not significant.
 

A ‘powerful message’

“It’s a powerful message to see an absolute 1.1% difference in the rate of thromboembolism and a trend to fewer major bleeds. I think this will change practice,” Dr. Spyropoulos added in the interview. “The next step is dissemination.”

But thromboprophylaxis experts cautioned that, while the results looked promising, the findings need more analysis and review, and the intervention may need further testing before it’s ready for widespread use.

For example, one unexpected result was an unexpected 2.1 percentage point increase in all-cause mortality linked with use of the decision-support tool. Total deaths from admission to 30 days after discharge occurred in 9.1% of the patients treated at the two hospitals that used the risk calculator and 7.0% among the control patients, a difference that Dr, Spyropoulos said was likely the result of unbalanced outcomes from COVID-19 infections that had no relevance to the tested intervention. The trial ran during December 2020–January 2022.
 

But wait – more detail and analysis needed

“I’d like to see more analysis of the data from this trial,” and “there is the issue of increased mortality,” commented Gregory Piazza, MD, director of vascular medicine at Brigham and Women’s Hospital in Boston, and a specialist in thromboembolism prevention and management. He also highlighted the need for greater detail on the arterial thromboembolic events tallied during the study.

With more details and analysis of these findings “we’ll learn more about the true impact” of this intervention, Dr. Piazza said in an interview.

Mitchel L. Zoler/MDedge News

“The increased mortality in the intervention group may have been due to differential treatment and decision-making and confounding and warrants further investigation,” commented Elaine M. Hylek, MD, a professor at Boston University and designated discussant for the report. Selection bias may have contributed to this possible confounding, Dr. Hylek noted.

Other limitations of the study cited by Dr. Hylek included its reliance on individual clinician decision-making to actually prescribe thromboprophylaxis, a lack of information on patient adherence to their thromboprophylaxis prescription, and an overall low rate of appropriate thromboprophylaxis prescribed to patients at discharge. The rates were 7.5% among the controls and 13.6% among patients in the intervention arm. For prescription at the time of hospitalization, the rates were 72.5% among control patients and 80.1% for patients seen at the two hospitals that used the decision-support tool.
 

The IMPROVE-DD VTE risk assessment tool

The clinical decision-support tool tested is called the IMPROVE-DD VTE risk assessment model, developed over several years by Dr. Spyropoulos and associates; they have also performed multiple validation studies. The model includes eight factors that score 1-3 points if positive that can add up to total scores of 0-14. A score of 0 or 1 is considered low risk, 2 or 3 intermediate risk, and 4 or more high risk. One of the scoring factors is the result of a D-dimer test, which explains the DD part of the name.

The eight factors and point assignments are prior venous thromboembolism: 3 points; known thrombophilia: 2 points; lower limb paralysis: 2 points; current cancer: 2 points; d-dimer level more than twofold the upper limit of normal: 2 points; immobilized for at least 7 days: 1 point; admitted to the ICU or coronary care unit: 1 point; and age greater than 60 years old: 1 point.

Development of the IMPROVE-DD VTE risk calculator received most of its funding from the U.S. Agency for Healthcare Research and Quality, and the risk tool will be available for hospitals and health systems to access at no charge through the agency’s website, Dr. Spyropoulos said. The researchers designed the calculator to operate in any EHR product.

IMPROVE-DD VTE “is a very valid, high-quality tool,” commented Dr. Piazza. “We’ve used some rather blunt tools in the past,” and especially praised inclusion of D-dimer results into the IMPROVE-DD VTE model.

“It’s nice to use a biomarker in addition to clinical factors,” he said. “A biomarker provides a more holistic picture; we can’t do genetic testing on every patient.”

Enrollment focused on higher-risk patients

The study ran at four academic, tertiary-care hospitals in the Northwell Health network in the New York region. It enrolled patients aged more than 60 years who were hospitalized for any of five diagnoses: heart failure; acute respiratory insufficiency, including chronic obstructive lung disease or asthma; acute infectious disease, including COVID-19; acute inflammatory disease, including rheumatic disease; or acute stroke. The study excluded patients with a history of atrial fibrillation, those who used an anticoagulant at home, or those who had received therapeutic anticoagulation within 24 hours of their hospital admission.

The anticoagulant prophylaxis that patients received depended on their calculated risk level – intermediate or high – and whether they were inpatients or being discharged. The anticoagulants that clinicians could prescribe included unfractionated heparin, enoxaparin, fondaparinux, rivaroxaban, and apixaban.

“We’ve been looking for a long time for a tool for medically ill patients that’s like the CHA2DS2-VASc score” for patients with atrial fibrillation. “These powerful data say we now have this, and the EHR provides a vehicle to easily implement it,” Dr. Spyropoulos said.

The IMPROVE-DD VTE study received partial funding from Janssen. Dr. Spyropoulos has been a consultant to Nayer, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Pfizer, and Sanofi; adviser to the ATLAS Group; and has received research support from Janssen. Dr. Piazza has received research funding from Bayer, BIG/EKOS, BMS, Janssen, and Portola. Dr. Hylek had been a consultant to Bayer and Ionis, and has received honoraria from Boehringer Ingelheim and Pfizer.

Noninvasive cosmetic treatments have been available for several years, but in the clinical experience of Jean Carruthers, MD, men have been slow to embrace them with the same gusto as women.

However, this could be changing as millennials – who tend to be more proactive about efforts to prevent skin aging – are getting older.

At a virtual course on laser and aesthetic skin therapy, Dr. Carruthers referred to the results of an online survey of 600 men aged 30-65 years conducted by Jared Jagdeo, MD, and colleagues in 2016, to gauge attitudes toward age-related changes of their facial features and their preferences for prioritizing treatment. The top five barriers to treatment cited by the respondents were: “I don’t think I need it yet” (47%); “concerned about safety/side effects” (46%); “concerned about injecting a foreign substance into my body” (45%); “cost” (42%), and “concerned my face won’t look natural” (41%).

“Since then, millennials took over as the largest portion of our workforce in North America,” said Dr. Carruthers who, with her husband, Alastair Carruthers, MD, pioneered the cosmetic use of onabotulinumtoxinA (Botox). “Millennials are interested in how they look and how to keep their aesthetic the best it can possibly be,” she said, so there may be “a generational aspect to this.”

Another factor that may affect the uptake of cosmetic procedures among men is the number of hours they spend gazing at their own image on a computer screen. Since the beginning of the COVID-19 pandemic, men have spent an increasing number of hours on video-conferencing calls via Zoom and other platforms, causing them to rethink how they view their appearance, Dr. Carruthers added. “Zoom dysmorphia” is the term that describes the phenomenon that developed during the pandemic where more patients expressed a desire to make changes to their appearance, including nose jobs and smoothing out forehead wrinkles.

“When we’re on a Zoom call, we’re spending 40% of our time looking at ourselves,” said Dr. Carruthers, clinical professor of ophthalmology and visual sciences at the University of British Columbia in Vancouver. “This would hint that the looking glass is not as powerful as the computer screen to motivate men” to pursue aesthetic treatments.

According to data from the American Society of Plastic Surgeons, the top 5 cosmetic surgical procedures performed in men in 2020 were nose shaping, eyelid surgery, cheek implants, liposuction, and ear surgery. The top 5 minimally-invasive procedures in men were botulinum toxin type A, followed by laser skin resurfacing, laser hair removal, soft tissue fillers, and microdermabrasion.

Why might men consider an injectable instead of surgery? Dr. Carruthers asked. “According to the 2016 survey by Dr. Jagdeo and colleagues, it’s to appear more youthful and to appear good for their age.”

From a clinical standpoint, success comes from understanding the subtle differences between treating men and women, she added.

In a 2022 article about optimizing skin tightening in aesthetics in men, Christian A. Albornoz, MD, and colleagues noted that in contrast to women, men “tend to have higher levels of collagen density and greater skin thickness, but these begin to decrease earlier on. They can also more frequently have severe photodamage”.

In another article published in 2018, Terrence Keaney, MD, and colleagues reviewed the objective data available on male aging and aesthetics. They stated that a “communication gap exists for men, as evidenced by the lack of information available online or by word of mouth about injectable treatments” and concluded that “educating men about available aesthetic treatments and about the safety and side effects associated with each treatment, as well as addressing concerns about their treatment results looking natural, are key considerations.”

That sentiment resonates with Dr. Carruthers. Part of the reason why men have not sought cosmetic treatments along with their female partners and friends seeking cosmetic treatments “is that they haven’t had anything in their cup,” she said. “Maybe this is something we need to think about, to try and help men come in and enjoy the positive benefits of aesthetic, noninvasive cosmetic treatments.”

The course was sponsored by Harvard Medical School, Massachusetts General Hospital, and Wellman Center for Photomedicine.

Dr. Carruthers disclosed that she is a consultant and researcher for Alastin, Appiell, Allergan Aesthetics, Avari Medical, Bonti, Evolus, Fount Bio, Jeune Aesthetics, Merz, and Revance Biopharma.

Noninvasive cosmetic treatments have been available for several years, but in the clinical experience of Jean Carruthers, MD, men have been slow to embrace them with the same gusto as women.

However, this could be changing as millennials – who tend to be more proactive about efforts to prevent skin aging – are getting older.

At a virtual course on laser and aesthetic skin therapy, Dr. Carruthers referred to the results of an online survey of 600 men aged 30-65 years conducted by Jared Jagdeo, MD, and colleagues in 2016, to gauge attitudes toward age-related changes of their facial features and their preferences for prioritizing treatment. The top five barriers to treatment cited by the respondents were: “I don’t think I need it yet” (47%); “concerned about safety/side effects” (46%); “concerned about injecting a foreign substance into my body” (45%); “cost” (42%), and “concerned my face won’t look natural” (41%).

“Since then, millennials took over as the largest portion of our workforce in North America,” said Dr. Carruthers who, with her husband, Alastair Carruthers, MD, pioneered the cosmetic use of onabotulinumtoxinA (Botox). “Millennials are interested in how they look and how to keep their aesthetic the best it can possibly be,” she said, so there may be “a generational aspect to this.”

Another factor that may affect the uptake of cosmetic procedures among men is the number of hours they spend gazing at their own image on a computer screen. Since the beginning of the COVID-19 pandemic, men have spent an increasing number of hours on video-conferencing calls via Zoom and other platforms, causing them to rethink how they view their appearance, Dr. Carruthers added. “Zoom dysmorphia” is the term that describes the phenomenon that developed during the pandemic where more patients expressed a desire to make changes to their appearance, including nose jobs and smoothing out forehead wrinkles.

“When we’re on a Zoom call, we’re spending 40% of our time looking at ourselves,” said Dr. Carruthers, clinical professor of ophthalmology and visual sciences at the University of British Columbia in Vancouver. “This would hint that the looking glass is not as powerful as the computer screen to motivate men” to pursue aesthetic treatments.

According to data from the American Society of Plastic Surgeons, the top 5 cosmetic surgical procedures performed in men in 2020 were nose shaping, eyelid surgery, cheek implants, liposuction, and ear surgery. The top 5 minimally-invasive procedures in men were botulinum toxin type A, followed by laser skin resurfacing, laser hair removal, soft tissue fillers, and microdermabrasion.

Why might men consider an injectable instead of surgery? Dr. Carruthers asked. “According to the 2016 survey by Dr. Jagdeo and colleagues, it’s to appear more youthful and to appear good for their age.”

From a clinical standpoint, success comes from understanding the subtle differences between treating men and women, she added.

In a 2022 article about optimizing skin tightening in aesthetics in men, Christian A. Albornoz, MD, and colleagues noted that in contrast to women, men “tend to have higher levels of collagen density and greater skin thickness, but these begin to decrease earlier on. They can also more frequently have severe photodamage”.

In another article published in 2018, Terrence Keaney, MD, and colleagues reviewed the objective data available on male aging and aesthetics. They stated that a “communication gap exists for men, as evidenced by the lack of information available online or by word of mouth about injectable treatments” and concluded that “educating men about available aesthetic treatments and about the safety and side effects associated with each treatment, as well as addressing concerns about their treatment results looking natural, are key considerations.”

That sentiment resonates with Dr. Carruthers. Part of the reason why men have not sought cosmetic treatments along with their female partners and friends seeking cosmetic treatments “is that they haven’t had anything in their cup,” she said. “Maybe this is something we need to think about, to try and help men come in and enjoy the positive benefits of aesthetic, noninvasive cosmetic treatments.”

The course was sponsored by Harvard Medical School, Massachusetts General Hospital, and Wellman Center for Photomedicine.

Dr. Carruthers disclosed that she is a consultant and researcher for Alastin, Appiell, Allergan Aesthetics, Avari Medical, Bonti, Evolus, Fount Bio, Jeune Aesthetics, Merz, and Revance Biopharma.

Noninvasive cosmetic treatments have been available for several years, but in the clinical experience of Jean Carruthers, MD, men have been slow to embrace them with the same gusto as women.

However, this could be changing as millennials – who tend to be more proactive about efforts to prevent skin aging – are getting older.

At a virtual course on laser and aesthetic skin therapy, Dr. Carruthers referred to the results of an online survey of 600 men aged 30-65 years conducted by Jared Jagdeo, MD, and colleagues in 2016, to gauge attitudes toward age-related changes of their facial features and their preferences for prioritizing treatment. The top five barriers to treatment cited by the respondents were: “I don’t think I need it yet” (47%); “concerned about safety/side effects” (46%); “concerned about injecting a foreign substance into my body” (45%); “cost” (42%), and “concerned my face won’t look natural” (41%).

“Since then, millennials took over as the largest portion of our workforce in North America,” said Dr. Carruthers who, with her husband, Alastair Carruthers, MD, pioneered the cosmetic use of onabotulinumtoxinA (Botox). “Millennials are interested in how they look and how to keep their aesthetic the best it can possibly be,” she said, so there may be “a generational aspect to this.”

Another factor that may affect the uptake of cosmetic procedures among men is the number of hours they spend gazing at their own image on a computer screen. Since the beginning of the COVID-19 pandemic, men have spent an increasing number of hours on video-conferencing calls via Zoom and other platforms, causing them to rethink how they view their appearance, Dr. Carruthers added. “Zoom dysmorphia” is the term that describes the phenomenon that developed during the pandemic where more patients expressed a desire to make changes to their appearance, including nose jobs and smoothing out forehead wrinkles.

“When we’re on a Zoom call, we’re spending 40% of our time looking at ourselves,” said Dr. Carruthers, clinical professor of ophthalmology and visual sciences at the University of British Columbia in Vancouver. “This would hint that the looking glass is not as powerful as the computer screen to motivate men” to pursue aesthetic treatments.

According to data from the American Society of Plastic Surgeons, the top 5 cosmetic surgical procedures performed in men in 2020 were nose shaping, eyelid surgery, cheek implants, liposuction, and ear surgery. The top 5 minimally-invasive procedures in men were botulinum toxin type A, followed by laser skin resurfacing, laser hair removal, soft tissue fillers, and microdermabrasion.

Why might men consider an injectable instead of surgery? Dr. Carruthers asked. “According to the 2016 survey by Dr. Jagdeo and colleagues, it’s to appear more youthful and to appear good for their age.”

From a clinical standpoint, success comes from understanding the subtle differences between treating men and women, she added.

In a 2022 article about optimizing skin tightening in aesthetics in men, Christian A. Albornoz, MD, and colleagues noted that in contrast to women, men “tend to have higher levels of collagen density and greater skin thickness, but these begin to decrease earlier on. They can also more frequently have severe photodamage”.

In another article published in 2018, Terrence Keaney, MD, and colleagues reviewed the objective data available on male aging and aesthetics. They stated that a “communication gap exists for men, as evidenced by the lack of information available online or by word of mouth about injectable treatments” and concluded that “educating men about available aesthetic treatments and about the safety and side effects associated with each treatment, as well as addressing concerns about their treatment results looking natural, are key considerations.”

That sentiment resonates with Dr. Carruthers. Part of the reason why men have not sought cosmetic treatments along with their female partners and friends seeking cosmetic treatments “is that they haven’t had anything in their cup,” she said. “Maybe this is something we need to think about, to try and help men come in and enjoy the positive benefits of aesthetic, noninvasive cosmetic treatments.”

The course was sponsored by Harvard Medical School, Massachusetts General Hospital, and Wellman Center for Photomedicine.

Dr. Carruthers disclosed that she is a consultant and researcher for Alastin, Appiell, Allergan Aesthetics, Avari Medical, Bonti, Evolus, Fount Bio, Jeune Aesthetics, Merz, and Revance Biopharma.

Vaccination campaigns in more than 80 nations have successfully reduced the prevalence of hepatitis B virus (HBV) surface antigen. That’s the good news.
 

Less good is the news that no countries are on track to meet the goals for HBV eradication by 2030 or 2050, and only 11 countries are on track to achieve all absolute or relative targets for hepatitis C virus (HCV) elimination, reported Sarah Blach, MHS, associate director of the Center for Disease Analysis Foundation, based in Lafayette, Colo.

“As countries progress toward eliminating hepatitis B and C, we really need to do more to expand political will and financing of national elimination programs. It’s great to see that it’s happening in some of these countries, but we really need that to expand,” she said at the annual meeting of the American Association for the Study of Liver Diseases.

Ms. Blach presented data from the foundation’s Polaris Observatory, an initiative that provides epidemiological data, modeling tools, training, and decision analytics to support eliminating HBV and HCV globally by 2030.

The investigators used mathematical disease burden models for HBV and HCV to assess worldwide trends toward viral elimination. They also evaluated HBV and HCV elimination policies as reported by authorities in various countries.

They forecast the year in which each country or territory would meet each of the World Health Organization’s four elimination targets from 110 HCV models and 166 HBV models. The targets are 90% diagnosed, 80% of the eligible population treated, 65% reduction in mortality, and 80% incidence reduction for HCV and either 95% incidence reduction or prevalence of 0.1% or less in children aged 5 years and younger for HBV.

Investigators summarized the results across countries by disease area and time period of elimination; that is, elimination before 2030, between 2031 and 2050, or after 2050.
 

Results for HCV and HBV targets

The 11 nations on track to achieve all absolute or relative (programmatic) targets for HCV by 2030 are Australia, Canada, Denmark, Egypt, Finland, France, Georgia, Japan, Norway, Spain, and the United Kingdom.

An additional 24 countries are on track to meet their goals for HCV between 2031 and 2050.

But the rest, including the United States, much of sub-Saharan Africa, China, and South Asia, are not on track to meet their goals for HCV by 2050.

No countries are on track to achieve the absolute or relative (programmatic) targets for elimination of HBV, Ms. Blach said.

However, 83 countries or territories, including the United States, are on track for achieving the HBV surface antigen prevalence target of less than 0.1% in children aged 5 years and younger by 2030.

Ms. Blach and colleagues also looked at results of quantitative policy surveys submitted by 61 countries. The respondents were asked to report on linkage to care, awareness and screening, monitoring and evaluation, ability to expand capacity, harm-reduction programs, financing of national programs, and political will to achieve targets.

The investigators scored countries on a scale of 1-10, with 10 being the highest score, in each category. For HCV, 25 countries (42%) had high scores, defined as 9 or 10, for political will, and 33 countries (54%) had high scores for national funding. For HBV, 17 countries (30%) received the high scores for political will, and 30 (51%) received the high scores for financing the national program.
 

The big picture

Most countries have not expanded HBV or HCV treatment beyond specialists, and HBV policies appear to lag behind policies directed toward HCV elimination, Ms. Blach noted.

“We do need to expand screening and treatment for hepatitis B moving forward,” she said.

The United States and the rest of the world need to do better, especially regarding HBV elimination, but the United States does appear to be making progress, said Richard Sterling, MD, MSc, from Virginia Commonwealth University, Richmond, who comoderated the session where Ms. Blach reported the data.

“My impression is that we’re doing a pretty good job with [HBV] vaccinations in the United States,” Dr. Sterling, who was not involved in the study, said in an interview.

One way to make progress, he said, may be to expand eligibility for HBV vaccines beyond the current upper age limit of 59 years.

Implementing simpler dosing regimens – the currently available vaccine is split into three doses – could improve vaccine compliance and lower costs, Dr. Sterling added.

During the session, Brian Conway, MD, medical director of the Vancouver Infectious Disease Centre, said it seems hard to use a composite set of data to determine a yes/no answer about whether a country is on track to reach targets.

“When you take my country of Canada, we have absolutely no national program, no hope of a national program, very little funding, and yet we make the cut. So how do you balance all these different variables to arrive at a yes/no answer and is there a way of putting a bit more subtlety into it?” Dr. Conway asked Ms. Blach.

Ms. Blach replied that the data are fluid, and countries can move closer or farther from reaching targets over time as conditions change.

Some countries seem to be improving efforts and “just need a bit more” work, Ms. Blach said.

“But we also saw some countries who we thought were going to be a shoo-in, and as time progressed the number of treatments just dropped in shocking ways. The reality is that a lot of countries are struggling to treat patients,” she said.

Canada “has a really great health system. It’s not a fragmented health system, and so even if you don’t have some of that push for elimination from the government level, having access to treatment, having access to those services, means that at least patients can come in and get what they need,” Ms. Blach said.

The study data are available for free on the Center for Disease Analysis Foundation’s Polaris website.

The study was funded by grants from the John C. Martin Foundation, ZeShan Foundation, EndHep2030, Gilead Sciences, and AbbVie. Ms. Blach is employed by the Center for Disease Analysis Foundation, which receives research grants from Gilead and AbbVie. Dr. Sterling and Dr. Conway reported no relevant disclosures.

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

Vaccination campaigns in more than 80 nations have successfully reduced the prevalence of hepatitis B virus (HBV) surface antigen. That’s the good news.
 

Less good is the news that no countries are on track to meet the goals for HBV eradication by 2030 or 2050, and only 11 countries are on track to achieve all absolute or relative targets for hepatitis C virus (HCV) elimination, reported Sarah Blach, MHS, associate director of the Center for Disease Analysis Foundation, based in Lafayette, Colo.

“As countries progress toward eliminating hepatitis B and C, we really need to do more to expand political will and financing of national elimination programs. It’s great to see that it’s happening in some of these countries, but we really need that to expand,” she said at the annual meeting of the American Association for the Study of Liver Diseases.

Ms. Blach presented data from the foundation’s Polaris Observatory, an initiative that provides epidemiological data, modeling tools, training, and decision analytics to support eliminating HBV and HCV globally by 2030.

The investigators used mathematical disease burden models for HBV and HCV to assess worldwide trends toward viral elimination. They also evaluated HBV and HCV elimination policies as reported by authorities in various countries.

They forecast the year in which each country or territory would meet each of the World Health Organization’s four elimination targets from 110 HCV models and 166 HBV models. The targets are 90% diagnosed, 80% of the eligible population treated, 65% reduction in mortality, and 80% incidence reduction for HCV and either 95% incidence reduction or prevalence of 0.1% or less in children aged 5 years and younger for HBV.

Investigators summarized the results across countries by disease area and time period of elimination; that is, elimination before 2030, between 2031 and 2050, or after 2050.
 

Results for HCV and HBV targets

The 11 nations on track to achieve all absolute or relative (programmatic) targets for HCV by 2030 are Australia, Canada, Denmark, Egypt, Finland, France, Georgia, Japan, Norway, Spain, and the United Kingdom.

An additional 24 countries are on track to meet their goals for HCV between 2031 and 2050.

But the rest, including the United States, much of sub-Saharan Africa, China, and South Asia, are not on track to meet their goals for HCV by 2050.

No countries are on track to achieve the absolute or relative (programmatic) targets for elimination of HBV, Ms. Blach said.

However, 83 countries or territories, including the United States, are on track for achieving the HBV surface antigen prevalence target of less than 0.1% in children aged 5 years and younger by 2030.

Ms. Blach and colleagues also looked at results of quantitative policy surveys submitted by 61 countries. The respondents were asked to report on linkage to care, awareness and screening, monitoring and evaluation, ability to expand capacity, harm-reduction programs, financing of national programs, and political will to achieve targets.

The investigators scored countries on a scale of 1-10, with 10 being the highest score, in each category. For HCV, 25 countries (42%) had high scores, defined as 9 or 10, for political will, and 33 countries (54%) had high scores for national funding. For HBV, 17 countries (30%) received the high scores for political will, and 30 (51%) received the high scores for financing the national program.
 

The big picture

Most countries have not expanded HBV or HCV treatment beyond specialists, and HBV policies appear to lag behind policies directed toward HCV elimination, Ms. Blach noted.

“We do need to expand screening and treatment for hepatitis B moving forward,” she said.

The United States and the rest of the world need to do better, especially regarding HBV elimination, but the United States does appear to be making progress, said Richard Sterling, MD, MSc, from Virginia Commonwealth University, Richmond, who comoderated the session where Ms. Blach reported the data.

“My impression is that we’re doing a pretty good job with [HBV] vaccinations in the United States,” Dr. Sterling, who was not involved in the study, said in an interview.

One way to make progress, he said, may be to expand eligibility for HBV vaccines beyond the current upper age limit of 59 years.

Implementing simpler dosing regimens – the currently available vaccine is split into three doses – could improve vaccine compliance and lower costs, Dr. Sterling added.

During the session, Brian Conway, MD, medical director of the Vancouver Infectious Disease Centre, said it seems hard to use a composite set of data to determine a yes/no answer about whether a country is on track to reach targets.

“When you take my country of Canada, we have absolutely no national program, no hope of a national program, very little funding, and yet we make the cut. So how do you balance all these different variables to arrive at a yes/no answer and is there a way of putting a bit more subtlety into it?” Dr. Conway asked Ms. Blach.

Ms. Blach replied that the data are fluid, and countries can move closer or farther from reaching targets over time as conditions change.

Some countries seem to be improving efforts and “just need a bit more” work, Ms. Blach said.

“But we also saw some countries who we thought were going to be a shoo-in, and as time progressed the number of treatments just dropped in shocking ways. The reality is that a lot of countries are struggling to treat patients,” she said.

Canada “has a really great health system. It’s not a fragmented health system, and so even if you don’t have some of that push for elimination from the government level, having access to treatment, having access to those services, means that at least patients can come in and get what they need,” Ms. Blach said.

The study data are available for free on the Center for Disease Analysis Foundation’s Polaris website.

The study was funded by grants from the John C. Martin Foundation, ZeShan Foundation, EndHep2030, Gilead Sciences, and AbbVie. Ms. Blach is employed by the Center for Disease Analysis Foundation, which receives research grants from Gilead and AbbVie. Dr. Sterling and Dr. Conway reported no relevant disclosures.

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

Vaccination campaigns in more than 80 nations have successfully reduced the prevalence of hepatitis B virus (HBV) surface antigen. That’s the good news.
 

Less good is the news that no countries are on track to meet the goals for HBV eradication by 2030 or 2050, and only 11 countries are on track to achieve all absolute or relative targets for hepatitis C virus (HCV) elimination, reported Sarah Blach, MHS, associate director of the Center for Disease Analysis Foundation, based in Lafayette, Colo.

“As countries progress toward eliminating hepatitis B and C, we really need to do more to expand political will and financing of national elimination programs. It’s great to see that it’s happening in some of these countries, but we really need that to expand,” she said at the annual meeting of the American Association for the Study of Liver Diseases.

Ms. Blach presented data from the foundation’s Polaris Observatory, an initiative that provides epidemiological data, modeling tools, training, and decision analytics to support eliminating HBV and HCV globally by 2030.

The investigators used mathematical disease burden models for HBV and HCV to assess worldwide trends toward viral elimination. They also evaluated HBV and HCV elimination policies as reported by authorities in various countries.

They forecast the year in which each country or territory would meet each of the World Health Organization’s four elimination targets from 110 HCV models and 166 HBV models. The targets are 90% diagnosed, 80% of the eligible population treated, 65% reduction in mortality, and 80% incidence reduction for HCV and either 95% incidence reduction or prevalence of 0.1% or less in children aged 5 years and younger for HBV.

Investigators summarized the results across countries by disease area and time period of elimination; that is, elimination before 2030, between 2031 and 2050, or after 2050.
 

Results for HCV and HBV targets

The 11 nations on track to achieve all absolute or relative (programmatic) targets for HCV by 2030 are Australia, Canada, Denmark, Egypt, Finland, France, Georgia, Japan, Norway, Spain, and the United Kingdom.

An additional 24 countries are on track to meet their goals for HCV between 2031 and 2050.

But the rest, including the United States, much of sub-Saharan Africa, China, and South Asia, are not on track to meet their goals for HCV by 2050.

No countries are on track to achieve the absolute or relative (programmatic) targets for elimination of HBV, Ms. Blach said.

However, 83 countries or territories, including the United States, are on track for achieving the HBV surface antigen prevalence target of less than 0.1% in children aged 5 years and younger by 2030.

Ms. Blach and colleagues also looked at results of quantitative policy surveys submitted by 61 countries. The respondents were asked to report on linkage to care, awareness and screening, monitoring and evaluation, ability to expand capacity, harm-reduction programs, financing of national programs, and political will to achieve targets.

The investigators scored countries on a scale of 1-10, with 10 being the highest score, in each category. For HCV, 25 countries (42%) had high scores, defined as 9 or 10, for political will, and 33 countries (54%) had high scores for national funding. For HBV, 17 countries (30%) received the high scores for political will, and 30 (51%) received the high scores for financing the national program.
 

The big picture

Most countries have not expanded HBV or HCV treatment beyond specialists, and HBV policies appear to lag behind policies directed toward HCV elimination, Ms. Blach noted.

“We do need to expand screening and treatment for hepatitis B moving forward,” she said.

The United States and the rest of the world need to do better, especially regarding HBV elimination, but the United States does appear to be making progress, said Richard Sterling, MD, MSc, from Virginia Commonwealth University, Richmond, who comoderated the session where Ms. Blach reported the data.

“My impression is that we’re doing a pretty good job with [HBV] vaccinations in the United States,” Dr. Sterling, who was not involved in the study, said in an interview.

One way to make progress, he said, may be to expand eligibility for HBV vaccines beyond the current upper age limit of 59 years.

Implementing simpler dosing regimens – the currently available vaccine is split into three doses – could improve vaccine compliance and lower costs, Dr. Sterling added.

During the session, Brian Conway, MD, medical director of the Vancouver Infectious Disease Centre, said it seems hard to use a composite set of data to determine a yes/no answer about whether a country is on track to reach targets.

“When you take my country of Canada, we have absolutely no national program, no hope of a national program, very little funding, and yet we make the cut. So how do you balance all these different variables to arrive at a yes/no answer and is there a way of putting a bit more subtlety into it?” Dr. Conway asked Ms. Blach.

Ms. Blach replied that the data are fluid, and countries can move closer or farther from reaching targets over time as conditions change.

Some countries seem to be improving efforts and “just need a bit more” work, Ms. Blach said.

“But we also saw some countries who we thought were going to be a shoo-in, and as time progressed the number of treatments just dropped in shocking ways. The reality is that a lot of countries are struggling to treat patients,” she said.

Canada “has a really great health system. It’s not a fragmented health system, and so even if you don’t have some of that push for elimination from the government level, having access to treatment, having access to those services, means that at least patients can come in and get what they need,” Ms. Blach said.

The study data are available for free on the Center for Disease Analysis Foundation’s Polaris website.

The study was funded by grants from the John C. Martin Foundation, ZeShan Foundation, EndHep2030, Gilead Sciences, and AbbVie. Ms. Blach is employed by the Center for Disease Analysis Foundation, which receives research grants from Gilead and AbbVie. Dr. Sterling and Dr. Conway reported no relevant disclosures.

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

Among people with nonalcoholic fatty liver disease (NAFLD), the fibrosis progression rate was higher among those who also had diabetes, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

NAFLD patients with type 2 diabetes progressed by one stage about every 6 years, compared with one stage about every 8 years among patients without diabetes, said Daniel Huang, MBBS, a visiting scholar at the University of California San Diego (UCSD) NAFLD Research Center and a transplant hepatologist at National University Hospital in Singapore.

“We now know that fibrosis stage is a major determinant of liver-related outcomes in NAFLD, as well as overall mortality,” he said. “Liver fibrosis progresses by approximately one stage every 7 years for individuals with NASH (nonalcoholic steatohepatitis).”

Recent UCSD data have indicated that about 14% of patients over age 50 with type 2 diabetes have NAFLD with advanced fibrosis, he noted. Previous studies have shown that diabetes is associated with higher rates of advanced fibrosis, cirrhosis, and hepatocellular carcinoma, but limited data exist around whether the fibrosis progression rate is higher among diabetics.
 

National study cohort

Dr. Huang and colleagues conducted a multicenter, multiethnic prospective cohort study within the NASH Clinical Research Network consortium to examine the fibrosis progression rate and the fibrosis regression rate among patients with or without diabetes. The study included adult participants at eight sites across the United States who had biopsy-confirmed NAFLD and available paired liver biopsies that were at least 1 year apart.

Clinical and laboratory data were obtained at enrollment and prospectively at 48-week intervals and recorded at the time of any liver biopsies. A central pathology committee conducted the liver histology assessment, and the entire pathology committee was blinded to clinical data and the sequence of liver biopsy. The fibrosis progression and regression rates were defined as the change in fibrosis stage over time between biopsies, measured in years.

The study comprised 447 adult participants with NAFLD: 208 patients with type 2 diabetes and 239 patients without diabetes, Dr. Huang said. The mean age was 51, and the mean body mass index was 34.7. The patients with diabetes were more likely to be older, to be women, and to have metabolic syndrome, NASH, and a higher fibrosis stage.

Notably, the median HbA1c among patients with diabetes was 6.8%, indicating a cohort with fairly well-controlled blood sugar. The median time between biopsies was 3.3 years.
 

Difference in progression, not regression

Overall, 151 participants (34%) experienced fibrosis progression, the primary study outcome. In a secondary outcome, 102 participants (23%) had fibrosis regression. The remaining 194 participants (43%) had no change in fibrosis stage. About 26% of patients with types 2 diabetes progressed to advanced fibrosis, as compared with 14.1% of patients without diabetes.

Among all those with fibrosis progression, the rate was 0.15 stages per year, with an average progression rate of one stage over 6.7 years. For patients with diabetes, the progression rate was significantly higher at 0.17 stages per year, compared with 0.13 stages per year among patients without diabetes, Dr. Huang said. That translated to an average progression of one stage over 5.9 years for patients with diabetes and 7.7 years for patients without diabetes.

In contrast, the regression rate was similar between those with or without diabetes at baseline, at –0.13 stages per year for those with diabetes versus –0.14 stages per year for those without diabetes. The similar outcome translated to an average regression of one stage over 7.7 years among those with diabetes and 7.1 years among those without diabetes.

Type 2 diabetes was an independent predictor of fibrosis progression in NAFLD, in both unadjusted and multivariable adjusted models, including baseline fibrosis stage, Dr. Huang said. In addition, patients with diabetes had a significantly higher cumulative incidence of fibrosis progression at 4 years (23% versus 19%), 8 years (59% versus 49%), and 12 years (93% versus 76%).

The research team didn’t find a significant difference in HbA1c as a predictor of fibrosis progression when using a cutoff of 7%.

“It is possible that poor glycemic control may accelerate fibrosis further, but we need studies to validate this,” Dr. Huang said. “These data have important implications for clinical practice and clinical trial design. Patients with NAFLD and diabetes may require more frequent monitoring for disease progression.”

The NASH Clinical Research Network consortium is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Huang has served on an advisory board for Eisai. The other authors declared various research support and advisory roles with numerous pharmaceutical companies.

Among people with nonalcoholic fatty liver disease (NAFLD), the fibrosis progression rate was higher among those who also had diabetes, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

NAFLD patients with type 2 diabetes progressed by one stage about every 6 years, compared with one stage about every 8 years among patients without diabetes, said Daniel Huang, MBBS, a visiting scholar at the University of California San Diego (UCSD) NAFLD Research Center and a transplant hepatologist at National University Hospital in Singapore.

“We now know that fibrosis stage is a major determinant of liver-related outcomes in NAFLD, as well as overall mortality,” he said. “Liver fibrosis progresses by approximately one stage every 7 years for individuals with NASH (nonalcoholic steatohepatitis).”

Recent UCSD data have indicated that about 14% of patients over age 50 with type 2 diabetes have NAFLD with advanced fibrosis, he noted. Previous studies have shown that diabetes is associated with higher rates of advanced fibrosis, cirrhosis, and hepatocellular carcinoma, but limited data exist around whether the fibrosis progression rate is higher among diabetics.
 

National study cohort

Dr. Huang and colleagues conducted a multicenter, multiethnic prospective cohort study within the NASH Clinical Research Network consortium to examine the fibrosis progression rate and the fibrosis regression rate among patients with or without diabetes. The study included adult participants at eight sites across the United States who had biopsy-confirmed NAFLD and available paired liver biopsies that were at least 1 year apart.

Clinical and laboratory data were obtained at enrollment and prospectively at 48-week intervals and recorded at the time of any liver biopsies. A central pathology committee conducted the liver histology assessment, and the entire pathology committee was blinded to clinical data and the sequence of liver biopsy. The fibrosis progression and regression rates were defined as the change in fibrosis stage over time between biopsies, measured in years.

The study comprised 447 adult participants with NAFLD: 208 patients with type 2 diabetes and 239 patients without diabetes, Dr. Huang said. The mean age was 51, and the mean body mass index was 34.7. The patients with diabetes were more likely to be older, to be women, and to have metabolic syndrome, NASH, and a higher fibrosis stage.

Notably, the median HbA1c among patients with diabetes was 6.8%, indicating a cohort with fairly well-controlled blood sugar. The median time between biopsies was 3.3 years.
 

Difference in progression, not regression

Overall, 151 participants (34%) experienced fibrosis progression, the primary study outcome. In a secondary outcome, 102 participants (23%) had fibrosis regression. The remaining 194 participants (43%) had no change in fibrosis stage. About 26% of patients with types 2 diabetes progressed to advanced fibrosis, as compared with 14.1% of patients without diabetes.

Among all those with fibrosis progression, the rate was 0.15 stages per year, with an average progression rate of one stage over 6.7 years. For patients with diabetes, the progression rate was significantly higher at 0.17 stages per year, compared with 0.13 stages per year among patients without diabetes, Dr. Huang said. That translated to an average progression of one stage over 5.9 years for patients with diabetes and 7.7 years for patients without diabetes.

In contrast, the regression rate was similar between those with or without diabetes at baseline, at –0.13 stages per year for those with diabetes versus –0.14 stages per year for those without diabetes. The similar outcome translated to an average regression of one stage over 7.7 years among those with diabetes and 7.1 years among those without diabetes.

Type 2 diabetes was an independent predictor of fibrosis progression in NAFLD, in both unadjusted and multivariable adjusted models, including baseline fibrosis stage, Dr. Huang said. In addition, patients with diabetes had a significantly higher cumulative incidence of fibrosis progression at 4 years (23% versus 19%), 8 years (59% versus 49%), and 12 years (93% versus 76%).

The research team didn’t find a significant difference in HbA1c as a predictor of fibrosis progression when using a cutoff of 7%.

“It is possible that poor glycemic control may accelerate fibrosis further, but we need studies to validate this,” Dr. Huang said. “These data have important implications for clinical practice and clinical trial design. Patients with NAFLD and diabetes may require more frequent monitoring for disease progression.”

The NASH Clinical Research Network consortium is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Huang has served on an advisory board for Eisai. The other authors declared various research support and advisory roles with numerous pharmaceutical companies.

Among people with nonalcoholic fatty liver disease (NAFLD), the fibrosis progression rate was higher among those who also had diabetes, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

NAFLD patients with type 2 diabetes progressed by one stage about every 6 years, compared with one stage about every 8 years among patients without diabetes, said Daniel Huang, MBBS, a visiting scholar at the University of California San Diego (UCSD) NAFLD Research Center and a transplant hepatologist at National University Hospital in Singapore.

“We now know that fibrosis stage is a major determinant of liver-related outcomes in NAFLD, as well as overall mortality,” he said. “Liver fibrosis progresses by approximately one stage every 7 years for individuals with NASH (nonalcoholic steatohepatitis).”

Recent UCSD data have indicated that about 14% of patients over age 50 with type 2 diabetes have NAFLD with advanced fibrosis, he noted. Previous studies have shown that diabetes is associated with higher rates of advanced fibrosis, cirrhosis, and hepatocellular carcinoma, but limited data exist around whether the fibrosis progression rate is higher among diabetics.
 

National study cohort

Dr. Huang and colleagues conducted a multicenter, multiethnic prospective cohort study within the NASH Clinical Research Network consortium to examine the fibrosis progression rate and the fibrosis regression rate among patients with or without diabetes. The study included adult participants at eight sites across the United States who had biopsy-confirmed NAFLD and available paired liver biopsies that were at least 1 year apart.

Clinical and laboratory data were obtained at enrollment and prospectively at 48-week intervals and recorded at the time of any liver biopsies. A central pathology committee conducted the liver histology assessment, and the entire pathology committee was blinded to clinical data and the sequence of liver biopsy. The fibrosis progression and regression rates were defined as the change in fibrosis stage over time between biopsies, measured in years.

The study comprised 447 adult participants with NAFLD: 208 patients with type 2 diabetes and 239 patients without diabetes, Dr. Huang said. The mean age was 51, and the mean body mass index was 34.7. The patients with diabetes were more likely to be older, to be women, and to have metabolic syndrome, NASH, and a higher fibrosis stage.

Notably, the median HbA1c among patients with diabetes was 6.8%, indicating a cohort with fairly well-controlled blood sugar. The median time between biopsies was 3.3 years.
 

Difference in progression, not regression

Overall, 151 participants (34%) experienced fibrosis progression, the primary study outcome. In a secondary outcome, 102 participants (23%) had fibrosis regression. The remaining 194 participants (43%) had no change in fibrosis stage. About 26% of patients with types 2 diabetes progressed to advanced fibrosis, as compared with 14.1% of patients without diabetes.

Among all those with fibrosis progression, the rate was 0.15 stages per year, with an average progression rate of one stage over 6.7 years. For patients with diabetes, the progression rate was significantly higher at 0.17 stages per year, compared with 0.13 stages per year among patients without diabetes, Dr. Huang said. That translated to an average progression of one stage over 5.9 years for patients with diabetes and 7.7 years for patients without diabetes.

In contrast, the regression rate was similar between those with or without diabetes at baseline, at –0.13 stages per year for those with diabetes versus –0.14 stages per year for those without diabetes. The similar outcome translated to an average regression of one stage over 7.7 years among those with diabetes and 7.1 years among those without diabetes.

Type 2 diabetes was an independent predictor of fibrosis progression in NAFLD, in both unadjusted and multivariable adjusted models, including baseline fibrosis stage, Dr. Huang said. In addition, patients with diabetes had a significantly higher cumulative incidence of fibrosis progression at 4 years (23% versus 19%), 8 years (59% versus 49%), and 12 years (93% versus 76%).

The research team didn’t find a significant difference in HbA1c as a predictor of fibrosis progression when using a cutoff of 7%.

“It is possible that poor glycemic control may accelerate fibrosis further, but we need studies to validate this,” Dr. Huang said. “These data have important implications for clinical practice and clinical trial design. Patients with NAFLD and diabetes may require more frequent monitoring for disease progression.”

The NASH Clinical Research Network consortium is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Huang has served on an advisory board for Eisai. The other authors declared various research support and advisory roles with numerous pharmaceutical companies.