Conference Coverage

PARIS – How can the problem of poor treatment compliance in patients with hypertension be resolved? A new therapeutic approach could be a game-changer.

Many approaches have been explored in recent years to make life easier for patients living with chronic conditions that require them to take daily medication: subcutaneous implantable devices, nanogels, and, more specifically in the case of hypertension, renal denervation or small interfering RNA (siRNA) with a long half-life.

It’s siRNA that Michel Azizi, MD, PhD, head of the blood pressure clinic at Georges Pompidou European Hospital (HEGP) in Paris, discussed at the International Meeting of the French Society of Hypertension.

These small molecules have already shown their worth in treating rare diseases such as transthyretin amyloidosis. More recently, treating hypercholesterolemia with the PCSK9 inhibitor inclisiran has proven effective. “One subcutaneous injection of inclisiran reduces LDL cholesterol by 50% for a period of 210 days,” said Dr. Azizi.

The benefit of a new therapeutic siRNA – zilebesiran, administered subcutaneously – in treating hypertension is currently the subject of a phase II clinical trial.

This is a double-stranded RNA. One of the strands is linked to a sugar, N-acetylgalactosamine (GalNAc), which protects these highly fragile siRNA and binds with a very strong affinity in the liver. The second strand binds to a specific area of the RNA to prevent synthesis of the precursor peptide of angiotensin, angiotensinogen. The resulting effect is suppression of the production of angiotensin I and II, which leads to a long-lasting lowering of blood pressure.
 

Lasting efficacy

Phase I studies with zilebesiran have demonstrated a long-term effect, with a reduction of greater than 90% in circulating angiotensinogen over 6 months after a single subcutaneous dose (800 mg). The peak in reduction of circulating angiotensinogen occurs after approximately 3 weeks.

“It’s extremely powerful,” said Dr. Azizi.

Lasting reductions in blood pressure have also been observed, with 24-hour ambulatory blood pressure monitoring showing a reduction in systolic BP of greater than 15 mm Hg 8 weeks after administration of a single dose of zilebesiran (800 mg).

Zilebesiran was also well tolerated, with only mild to moderate reactions at the site of the injection (n = 5/56) and no serious treatment-related adverse events, hypotension, or significant changes in kidney or liver function.

“In terms of benefits, the effect is ongoing. Zilebesiran leads to reduced medication use and causes less variability in blood pressure response. Nevertheless, interfering RNA acts slowly, meaning that zilebesiran would not be suitable for people presenting with a hypertensive crisis. The fact that it blocks the renin-angiotensin system [RAS] for a very long period of time also poses the question of how to reverse its hypotensive effects,” said Dr. Azizi.
 

Unanswered questions

The lasting RAS antagonist and blood pressure–lowering effects pose a potential safety problem in circumstances involving patients in a state of hypovolemia and hypotension who require rapid blood pressure–raising interventions to prevent morbidity and mortality.

In recent studies, Estrellita Uijl et al. have thus examined strategies to counteract the blood pressure–lowering effect of siRNA in spontaneously hypertensive rats.

Fludrocortisone and a high-salt diet were both successful in gradually increasing blood pressure, which returned to its baseline levels on days 5 and 7, respectively. Yet this rate of response would be wholly inadequate in an urgent clinical situation.

However, midodrine could not reduce blood pressure to normal levels, whether administered subcutaneously or orally.

A rapid and short-lasting increase in blood pressure was observed with bolus doses of vasopressors, but clinically, these would need to be administered intravenously to achieve a lasting effect. Such administration would require hospitalization, close monitoring, and the use of human resources and additional health care provisions.

Encouragingly, the laboratory that created this molecule, Alnylam Pharmaceuticals, has come up with an antidote: Reversir. It is a GalNAc-conjugated, single-stranded, high-affinity oligonucleotide complementary to the zilebesiran strand that achieves effective reversal of siRNA activity in 24 hours.

In the future, after the phase 2 trials have been completed, whether or not zilebesiran reduces the incidence of cardiovascular events and mortality remains to be seen. But as for Dr. Azizi, the director of HEGP’s blood pressure clinic in Paris, he has no doubt that “this approach is about to shake up how we treat patients in the cardiovascular field.”
 

On the horizon

Zilebesiran is being studied in phase 2 trials in patients with mild to moderate hypertension not taking antihypertensive drugs (KARDIA-1: 375 patients; double-blind, placebo-controlled, five-arm trial; zilebesiran at 150, 300, and 600 mg twice per year and 300 mg once every 3 months) and in patients whose blood pressure is not controlled (KARDIA-2: 800 patients; initial open-label start-up period of 4 weeks with indapamide/amlodipine/olmesartan, followed by a double-blind, placebo-controlled study over 6 months, then an open-label extension study for up to 12 additional months; zilebesiran at 600 mg on the first day of the initial double-blind period, then every 6 months during the open-label extension period).

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

PARIS – How can the problem of poor treatment compliance in patients with hypertension be resolved? A new therapeutic approach could be a game-changer.

Many approaches have been explored in recent years to make life easier for patients living with chronic conditions that require them to take daily medication: subcutaneous implantable devices, nanogels, and, more specifically in the case of hypertension, renal denervation or small interfering RNA (siRNA) with a long half-life.

It’s siRNA that Michel Azizi, MD, PhD, head of the blood pressure clinic at Georges Pompidou European Hospital (HEGP) in Paris, discussed at the International Meeting of the French Society of Hypertension.

These small molecules have already shown their worth in treating rare diseases such as transthyretin amyloidosis. More recently, treating hypercholesterolemia with the PCSK9 inhibitor inclisiran has proven effective. “One subcutaneous injection of inclisiran reduces LDL cholesterol by 50% for a period of 210 days,” said Dr. Azizi.

The benefit of a new therapeutic siRNA – zilebesiran, administered subcutaneously – in treating hypertension is currently the subject of a phase II clinical trial.

This is a double-stranded RNA. One of the strands is linked to a sugar, N-acetylgalactosamine (GalNAc), which protects these highly fragile siRNA and binds with a very strong affinity in the liver. The second strand binds to a specific area of the RNA to prevent synthesis of the precursor peptide of angiotensin, angiotensinogen. The resulting effect is suppression of the production of angiotensin I and II, which leads to a long-lasting lowering of blood pressure.
 

Lasting efficacy

Phase I studies with zilebesiran have demonstrated a long-term effect, with a reduction of greater than 90% in circulating angiotensinogen over 6 months after a single subcutaneous dose (800 mg). The peak in reduction of circulating angiotensinogen occurs after approximately 3 weeks.

“It’s extremely powerful,” said Dr. Azizi.

Lasting reductions in blood pressure have also been observed, with 24-hour ambulatory blood pressure monitoring showing a reduction in systolic BP of greater than 15 mm Hg 8 weeks after administration of a single dose of zilebesiran (800 mg).

Zilebesiran was also well tolerated, with only mild to moderate reactions at the site of the injection (n = 5/56) and no serious treatment-related adverse events, hypotension, or significant changes in kidney or liver function.

“In terms of benefits, the effect is ongoing. Zilebesiran leads to reduced medication use and causes less variability in blood pressure response. Nevertheless, interfering RNA acts slowly, meaning that zilebesiran would not be suitable for people presenting with a hypertensive crisis. The fact that it blocks the renin-angiotensin system [RAS] for a very long period of time also poses the question of how to reverse its hypotensive effects,” said Dr. Azizi.
 

Unanswered questions

The lasting RAS antagonist and blood pressure–lowering effects pose a potential safety problem in circumstances involving patients in a state of hypovolemia and hypotension who require rapid blood pressure–raising interventions to prevent morbidity and mortality.

In recent studies, Estrellita Uijl et al. have thus examined strategies to counteract the blood pressure–lowering effect of siRNA in spontaneously hypertensive rats.

Fludrocortisone and a high-salt diet were both successful in gradually increasing blood pressure, which returned to its baseline levels on days 5 and 7, respectively. Yet this rate of response would be wholly inadequate in an urgent clinical situation.

However, midodrine could not reduce blood pressure to normal levels, whether administered subcutaneously or orally.

A rapid and short-lasting increase in blood pressure was observed with bolus doses of vasopressors, but clinically, these would need to be administered intravenously to achieve a lasting effect. Such administration would require hospitalization, close monitoring, and the use of human resources and additional health care provisions.

Encouragingly, the laboratory that created this molecule, Alnylam Pharmaceuticals, has come up with an antidote: Reversir. It is a GalNAc-conjugated, single-stranded, high-affinity oligonucleotide complementary to the zilebesiran strand that achieves effective reversal of siRNA activity in 24 hours.

In the future, after the phase 2 trials have been completed, whether or not zilebesiran reduces the incidence of cardiovascular events and mortality remains to be seen. But as for Dr. Azizi, the director of HEGP’s blood pressure clinic in Paris, he has no doubt that “this approach is about to shake up how we treat patients in the cardiovascular field.”
 

On the horizon

Zilebesiran is being studied in phase 2 trials in patients with mild to moderate hypertension not taking antihypertensive drugs (KARDIA-1: 375 patients; double-blind, placebo-controlled, five-arm trial; zilebesiran at 150, 300, and 600 mg twice per year and 300 mg once every 3 months) and in patients whose blood pressure is not controlled (KARDIA-2: 800 patients; initial open-label start-up period of 4 weeks with indapamide/amlodipine/olmesartan, followed by a double-blind, placebo-controlled study over 6 months, then an open-label extension study for up to 12 additional months; zilebesiran at 600 mg on the first day of the initial double-blind period, then every 6 months during the open-label extension period).

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

PARIS – How can the problem of poor treatment compliance in patients with hypertension be resolved? A new therapeutic approach could be a game-changer.

Many approaches have been explored in recent years to make life easier for patients living with chronic conditions that require them to take daily medication: subcutaneous implantable devices, nanogels, and, more specifically in the case of hypertension, renal denervation or small interfering RNA (siRNA) with a long half-life.

It’s siRNA that Michel Azizi, MD, PhD, head of the blood pressure clinic at Georges Pompidou European Hospital (HEGP) in Paris, discussed at the International Meeting of the French Society of Hypertension.

These small molecules have already shown their worth in treating rare diseases such as transthyretin amyloidosis. More recently, treating hypercholesterolemia with the PCSK9 inhibitor inclisiran has proven effective. “One subcutaneous injection of inclisiran reduces LDL cholesterol by 50% for a period of 210 days,” said Dr. Azizi.

The benefit of a new therapeutic siRNA – zilebesiran, administered subcutaneously – in treating hypertension is currently the subject of a phase II clinical trial.

This is a double-stranded RNA. One of the strands is linked to a sugar, N-acetylgalactosamine (GalNAc), which protects these highly fragile siRNA and binds with a very strong affinity in the liver. The second strand binds to a specific area of the RNA to prevent synthesis of the precursor peptide of angiotensin, angiotensinogen. The resulting effect is suppression of the production of angiotensin I and II, which leads to a long-lasting lowering of blood pressure.
 

Lasting efficacy

Phase I studies with zilebesiran have demonstrated a long-term effect, with a reduction of greater than 90% in circulating angiotensinogen over 6 months after a single subcutaneous dose (800 mg). The peak in reduction of circulating angiotensinogen occurs after approximately 3 weeks.

“It’s extremely powerful,” said Dr. Azizi.

Lasting reductions in blood pressure have also been observed, with 24-hour ambulatory blood pressure monitoring showing a reduction in systolic BP of greater than 15 mm Hg 8 weeks after administration of a single dose of zilebesiran (800 mg).

Zilebesiran was also well tolerated, with only mild to moderate reactions at the site of the injection (n = 5/56) and no serious treatment-related adverse events, hypotension, or significant changes in kidney or liver function.

“In terms of benefits, the effect is ongoing. Zilebesiran leads to reduced medication use and causes less variability in blood pressure response. Nevertheless, interfering RNA acts slowly, meaning that zilebesiran would not be suitable for people presenting with a hypertensive crisis. The fact that it blocks the renin-angiotensin system [RAS] for a very long period of time also poses the question of how to reverse its hypotensive effects,” said Dr. Azizi.
 

Unanswered questions

The lasting RAS antagonist and blood pressure–lowering effects pose a potential safety problem in circumstances involving patients in a state of hypovolemia and hypotension who require rapid blood pressure–raising interventions to prevent morbidity and mortality.

In recent studies, Estrellita Uijl et al. have thus examined strategies to counteract the blood pressure–lowering effect of siRNA in spontaneously hypertensive rats.

Fludrocortisone and a high-salt diet were both successful in gradually increasing blood pressure, which returned to its baseline levels on days 5 and 7, respectively. Yet this rate of response would be wholly inadequate in an urgent clinical situation.

However, midodrine could not reduce blood pressure to normal levels, whether administered subcutaneously or orally.

A rapid and short-lasting increase in blood pressure was observed with bolus doses of vasopressors, but clinically, these would need to be administered intravenously to achieve a lasting effect. Such administration would require hospitalization, close monitoring, and the use of human resources and additional health care provisions.

Encouragingly, the laboratory that created this molecule, Alnylam Pharmaceuticals, has come up with an antidote: Reversir. It is a GalNAc-conjugated, single-stranded, high-affinity oligonucleotide complementary to the zilebesiran strand that achieves effective reversal of siRNA activity in 24 hours.

In the future, after the phase 2 trials have been completed, whether or not zilebesiran reduces the incidence of cardiovascular events and mortality remains to be seen. But as for Dr. Azizi, the director of HEGP’s blood pressure clinic in Paris, he has no doubt that “this approach is about to shake up how we treat patients in the cardiovascular field.”
 

On the horizon

Zilebesiran is being studied in phase 2 trials in patients with mild to moderate hypertension not taking antihypertensive drugs (KARDIA-1: 375 patients; double-blind, placebo-controlled, five-arm trial; zilebesiran at 150, 300, and 600 mg twice per year and 300 mg once every 3 months) and in patients whose blood pressure is not controlled (KARDIA-2: 800 patients; initial open-label start-up period of 4 weeks with indapamide/amlodipine/olmesartan, followed by a double-blind, placebo-controlled study over 6 months, then an open-label extension study for up to 12 additional months; zilebesiran at 600 mg on the first day of the initial double-blind period, then every 6 months during the open-label extension period).

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

Atrial dysfunction, widely considered a marker or consequence of other heart diseases, is a relevant clinical entity, which is why it is justified to define atrial failure or insufficiency as “a new syndrome that all cardiologists should be aware of,” said Adrián Baranchuk, MD, PhD, professor of medicine at Queen’s University, Kingston, Ont., during the 2022 48th Argentine Congress of Cardiology in Buenos Aires.

“The atria are like the heart’s silly sisters and can fail just like the ventricle fails. Understanding their function and dysfunction helps us to understand heart failure. And as electrophysiologists and clinical cardiologists, we have to embrace this concept and understand it in depth,” Dr. Baranchuk, president-elect of the Inter-American Society of Cardiology, said in an interview.

The specialist first proposed atrial failure as an entity or syndrome in early 2020 in an article in the Journal of the American College of Cardiology. His four collaborators included the experienced Eugene Braunwald, MD, from Brigham and Women’s Hospital, Boston, and Antoni Bayés de Luna, PhD, from the department of medicine of the autonomous University of Barcelona.
 

Pathology despite function

“In many patients with heart failure, the pump function is preserved, but what causes the pathology? For the last 5-10 years, attention has been focused on the ventricle: whether it contracts poorly or whether it contracts properly and relaxes poorly. However, we have also seen patients in whom the ventricle contracts properly and relaxes properly. Where else can we look? We started looking at atrial contraction, especially the left atrium,” recalled Dr. Baranchuk.

He and his colleagues proposed the following consensus definition of atrial failure or insufficiency: any atrial dysfunction (anatomical, mechanical, electrical, and rheological, including blood homeostasis) that causes impaired function, heart symptoms, and a worsening of quality of life (or life expectancy) in the absence of significant valvular or ventricular abnormalities.

In his presentation, recorded and projected by video from Canada, Dr. Baranchuk pointed out that there are two large groups of causes of atrial failure: one that has to do with electrical disorders of atrial and interatrial contraction and another related to the progressive development of fibrosis, which gradually leads to dyssynchrony in interatrial contraction, pump failure, and impaired atrial function as a reservoir and as a conduit.

“In turn, these mechanisms trigger neurohormonal alterations that perpetuate atrial failure, so it is not just a matter of progressive fibrosis, which is very difficult to treat, but also of constant neurohormonal activation that guarantees that these phenomena never resolve,” said Dr. Baranchuk. The manifestations or end point of this cascade of events are the known ones: stroke, ischemia, and heart failure.
 

New entity necessary?

Defining atrial failure or insufficiency as a clinical entity not only restores the hierarchy of the atria in cardiac function, which was already postulated by William Harvey in 1628, but also enables new lines of research that would eventually allow timely preventive interventions.

One key is early recognition of partial or total interatrial block by analyzing the characteristics of the P wave on the electrocardiogram, which could serve to prevent progression to atrial fibrillation. Left atrial enlargement can also be detected by echocardiography.

“When the contractile impairment is severe and you are in atrial fibrillation, all that remains is to apply patches. The strategy is to correct risk factors beforehand, such as high blood pressure, sleep apnea, or high-dose alcohol consumption, as well as tirelessly searching for atrial fibrillation, with Holter electrocardiograms, continuous monitoring devices, such as Apple Watch, KardiaMobile, or an implantable loop recorder,” Dr. Baranchuk said in an interview.

Two ongoing or planned studies, ARCADIA and AMIABLE, will seek to determine whether anticoagulation in patients with elevated cardiovascular risk scores and any of these atrial disorders that have not yet led to atrial fibrillation could reduce the incidence of stroke.

The strategy has a rational basis. In a subanalysis of raw data from the NAVIGATE ESUS study in patients with embolic stroke of unknown cause, Dr. Baranchuk estimated that the presence of interatrial block was a tenfold higher predictor of the risk of experiencing a second stroke. Another 2018 observational study in which he participated found that in outpatients with heart failure, advanced interatrial block approximately tripled the risk of developing atrial fibrillation and ischemic stroke.

For Dr. Baranchuk, other questions that still need to be answered include whether drugs used for heart failure with preserved ejection fraction can be useful in primary atrial failure or whether specific drugs can be repositioned or developed to suppress or slow the process of fibrosis. “From generating the clinical concept, many lines of research are enabled.”

“The concept of atrial failure is very interesting and opens our eyes to treatments,” another speaker at the session, Alejo Tronconi, MD, a cardiologist and electrophysiologist at the Cardiovascular Institute of the South, Cipolletti, Argentina, said in an interview.

“It is necessary to cut circuits that have been extensively studied in heart failure models, and now we are beginning to see their participation in atrial dysfunction,” he said.

Dr. Baranchuk and Dr. Tronconi declared no relevant financial conflict of interest.

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

Atrial dysfunction, widely considered a marker or consequence of other heart diseases, is a relevant clinical entity, which is why it is justified to define atrial failure or insufficiency as “a new syndrome that all cardiologists should be aware of,” said Adrián Baranchuk, MD, PhD, professor of medicine at Queen’s University, Kingston, Ont., during the 2022 48th Argentine Congress of Cardiology in Buenos Aires.

“The atria are like the heart’s silly sisters and can fail just like the ventricle fails. Understanding their function and dysfunction helps us to understand heart failure. And as electrophysiologists and clinical cardiologists, we have to embrace this concept and understand it in depth,” Dr. Baranchuk, president-elect of the Inter-American Society of Cardiology, said in an interview.

The specialist first proposed atrial failure as an entity or syndrome in early 2020 in an article in the Journal of the American College of Cardiology. His four collaborators included the experienced Eugene Braunwald, MD, from Brigham and Women’s Hospital, Boston, and Antoni Bayés de Luna, PhD, from the department of medicine of the autonomous University of Barcelona.
 

Pathology despite function

“In many patients with heart failure, the pump function is preserved, but what causes the pathology? For the last 5-10 years, attention has been focused on the ventricle: whether it contracts poorly or whether it contracts properly and relaxes poorly. However, we have also seen patients in whom the ventricle contracts properly and relaxes properly. Where else can we look? We started looking at atrial contraction, especially the left atrium,” recalled Dr. Baranchuk.

He and his colleagues proposed the following consensus definition of atrial failure or insufficiency: any atrial dysfunction (anatomical, mechanical, electrical, and rheological, including blood homeostasis) that causes impaired function, heart symptoms, and a worsening of quality of life (or life expectancy) in the absence of significant valvular or ventricular abnormalities.

In his presentation, recorded and projected by video from Canada, Dr. Baranchuk pointed out that there are two large groups of causes of atrial failure: one that has to do with electrical disorders of atrial and interatrial contraction and another related to the progressive development of fibrosis, which gradually leads to dyssynchrony in interatrial contraction, pump failure, and impaired atrial function as a reservoir and as a conduit.

“In turn, these mechanisms trigger neurohormonal alterations that perpetuate atrial failure, so it is not just a matter of progressive fibrosis, which is very difficult to treat, but also of constant neurohormonal activation that guarantees that these phenomena never resolve,” said Dr. Baranchuk. The manifestations or end point of this cascade of events are the known ones: stroke, ischemia, and heart failure.
 

New entity necessary?

Defining atrial failure or insufficiency as a clinical entity not only restores the hierarchy of the atria in cardiac function, which was already postulated by William Harvey in 1628, but also enables new lines of research that would eventually allow timely preventive interventions.

One key is early recognition of partial or total interatrial block by analyzing the characteristics of the P wave on the electrocardiogram, which could serve to prevent progression to atrial fibrillation. Left atrial enlargement can also be detected by echocardiography.

“When the contractile impairment is severe and you are in atrial fibrillation, all that remains is to apply patches. The strategy is to correct risk factors beforehand, such as high blood pressure, sleep apnea, or high-dose alcohol consumption, as well as tirelessly searching for atrial fibrillation, with Holter electrocardiograms, continuous monitoring devices, such as Apple Watch, KardiaMobile, or an implantable loop recorder,” Dr. Baranchuk said in an interview.

Two ongoing or planned studies, ARCADIA and AMIABLE, will seek to determine whether anticoagulation in patients with elevated cardiovascular risk scores and any of these atrial disorders that have not yet led to atrial fibrillation could reduce the incidence of stroke.

The strategy has a rational basis. In a subanalysis of raw data from the NAVIGATE ESUS study in patients with embolic stroke of unknown cause, Dr. Baranchuk estimated that the presence of interatrial block was a tenfold higher predictor of the risk of experiencing a second stroke. Another 2018 observational study in which he participated found that in outpatients with heart failure, advanced interatrial block approximately tripled the risk of developing atrial fibrillation and ischemic stroke.

For Dr. Baranchuk, other questions that still need to be answered include whether drugs used for heart failure with preserved ejection fraction can be useful in primary atrial failure or whether specific drugs can be repositioned or developed to suppress or slow the process of fibrosis. “From generating the clinical concept, many lines of research are enabled.”

“The concept of atrial failure is very interesting and opens our eyes to treatments,” another speaker at the session, Alejo Tronconi, MD, a cardiologist and electrophysiologist at the Cardiovascular Institute of the South, Cipolletti, Argentina, said in an interview.

“It is necessary to cut circuits that have been extensively studied in heart failure models, and now we are beginning to see their participation in atrial dysfunction,” he said.

Dr. Baranchuk and Dr. Tronconi declared no relevant financial conflict of interest.

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

Atrial dysfunction, widely considered a marker or consequence of other heart diseases, is a relevant clinical entity, which is why it is justified to define atrial failure or insufficiency as “a new syndrome that all cardiologists should be aware of,” said Adrián Baranchuk, MD, PhD, professor of medicine at Queen’s University, Kingston, Ont., during the 2022 48th Argentine Congress of Cardiology in Buenos Aires.

“The atria are like the heart’s silly sisters and can fail just like the ventricle fails. Understanding their function and dysfunction helps us to understand heart failure. And as electrophysiologists and clinical cardiologists, we have to embrace this concept and understand it in depth,” Dr. Baranchuk, president-elect of the Inter-American Society of Cardiology, said in an interview.

The specialist first proposed atrial failure as an entity or syndrome in early 2020 in an article in the Journal of the American College of Cardiology. His four collaborators included the experienced Eugene Braunwald, MD, from Brigham and Women’s Hospital, Boston, and Antoni Bayés de Luna, PhD, from the department of medicine of the autonomous University of Barcelona.
 

Pathology despite function

“In many patients with heart failure, the pump function is preserved, but what causes the pathology? For the last 5-10 years, attention has been focused on the ventricle: whether it contracts poorly or whether it contracts properly and relaxes poorly. However, we have also seen patients in whom the ventricle contracts properly and relaxes properly. Where else can we look? We started looking at atrial contraction, especially the left atrium,” recalled Dr. Baranchuk.

He and his colleagues proposed the following consensus definition of atrial failure or insufficiency: any atrial dysfunction (anatomical, mechanical, electrical, and rheological, including blood homeostasis) that causes impaired function, heart symptoms, and a worsening of quality of life (or life expectancy) in the absence of significant valvular or ventricular abnormalities.

In his presentation, recorded and projected by video from Canada, Dr. Baranchuk pointed out that there are two large groups of causes of atrial failure: one that has to do with electrical disorders of atrial and interatrial contraction and another related to the progressive development of fibrosis, which gradually leads to dyssynchrony in interatrial contraction, pump failure, and impaired atrial function as a reservoir and as a conduit.

“In turn, these mechanisms trigger neurohormonal alterations that perpetuate atrial failure, so it is not just a matter of progressive fibrosis, which is very difficult to treat, but also of constant neurohormonal activation that guarantees that these phenomena never resolve,” said Dr. Baranchuk. The manifestations or end point of this cascade of events are the known ones: stroke, ischemia, and heart failure.
 

New entity necessary?

Defining atrial failure or insufficiency as a clinical entity not only restores the hierarchy of the atria in cardiac function, which was already postulated by William Harvey in 1628, but also enables new lines of research that would eventually allow timely preventive interventions.

One key is early recognition of partial or total interatrial block by analyzing the characteristics of the P wave on the electrocardiogram, which could serve to prevent progression to atrial fibrillation. Left atrial enlargement can also be detected by echocardiography.

“When the contractile impairment is severe and you are in atrial fibrillation, all that remains is to apply patches. The strategy is to correct risk factors beforehand, such as high blood pressure, sleep apnea, or high-dose alcohol consumption, as well as tirelessly searching for atrial fibrillation, with Holter electrocardiograms, continuous monitoring devices, such as Apple Watch, KardiaMobile, or an implantable loop recorder,” Dr. Baranchuk said in an interview.

Two ongoing or planned studies, ARCADIA and AMIABLE, will seek to determine whether anticoagulation in patients with elevated cardiovascular risk scores and any of these atrial disorders that have not yet led to atrial fibrillation could reduce the incidence of stroke.

The strategy has a rational basis. In a subanalysis of raw data from the NAVIGATE ESUS study in patients with embolic stroke of unknown cause, Dr. Baranchuk estimated that the presence of interatrial block was a tenfold higher predictor of the risk of experiencing a second stroke. Another 2018 observational study in which he participated found that in outpatients with heart failure, advanced interatrial block approximately tripled the risk of developing atrial fibrillation and ischemic stroke.

For Dr. Baranchuk, other questions that still need to be answered include whether drugs used for heart failure with preserved ejection fraction can be useful in primary atrial failure or whether specific drugs can be repositioned or developed to suppress or slow the process of fibrosis. “From generating the clinical concept, many lines of research are enabled.”

“The concept of atrial failure is very interesting and opens our eyes to treatments,” another speaker at the session, Alejo Tronconi, MD, a cardiologist and electrophysiologist at the Cardiovascular Institute of the South, Cipolletti, Argentina, said in an interview.

“It is necessary to cut circuits that have been extensively studied in heart failure models, and now we are beginning to see their participation in atrial dysfunction,” he said.

Dr. Baranchuk and Dr. Tronconi declared no relevant financial conflict of interest.

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

SAN DIEGO – When picosecond lasers hit the market about 10 years ago, they became a game-changer for tattoo removal, boasting the delivery of energy that is about threefold faster than with nanosecond lasers.

However, picosecond lasers are far from perfect even in the hands of the most experienced clinicians, according to Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford. “They have been very difficult to build from an engineering perspective,” he said at the annual Masters of Aesthetics Symposium. It took a long time for these lasers to come to the market, and they are still fairly expensive and require a lot of maintenance, he noted. In addition, “they are also not quite as ‘picosecond’ as they need to be. I think there is definitely room to improve, but this is the gold standard.”

Today, most clinicians use Q-switched nanosecond and picosecond lasers for tattoo removal, though appropriate wavelengths need to be selected based on the tattoo ink color. Tattoo ink particles average about 0.1 mcm in size, and the thermal relaxation size works out to be less than 10 nanoseconds, with shorter pulses better at capturing the ink particles that are smaller than average.

Lance Sitton Photography/Thinkstock

Black is the most common tattoo color dermatologists treat. “For that, you can typically use a 1064, which has the highest absorption, but you can also use many of the other wavelengths,” he said. “Other colors are less common, followed by red, for which you would use a 532-nm wavelength.”

Dr. Ibrahimi underscored the importance of setting realistic expectations during consults with patients seeking options for tattoo removal. Even with picosecond laser technology, many treatments are typically required and “a good patient consultation is key to setting proper expectations,” he said. “If you promise someone results in 4 to 5 treatments like many of the device companies will say you can achieve, you’re going to have a large group of patients who are disappointed.”

The clinical endpoint to strive for during tattoo removal is whitening of the ink, which typically fades about 20 minutes after treatment. That whitening corresponds to cavitation, or the production of gas vacuoles in the cells that were holding the ink. This discovery led to a technique intended to enhance tattoo removal. In 2012, R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and colleagues published results of a study that compared a single Q-switched laser treatment pass with four treatment passes separated by 20 minutes. After treating 18 tattoos in 12 adults, they found that the technique, known as the “R20” method, was more effective than a single-pass treatment (P < .01).

“Subsequent to this, there has been conflicting data on whether this is truly effective or not,” said Dr. Ibrahimi, who is also on the board of directors for the American Society for Dermatologic Surgery and the American Society for Laser Medicine and Surgery. “Most of us agree that one additional pass would be helpful, but when you’re doing this in the private practice setting, it’s often challenging because patients aren’t necessarily willing to pay more for more than just one pass for their tattoo removal.”

Another recent advance is use of a topical square silicone patch infused with perfluorodecalin (PFD) for use during tattoo removal, which has been shown to reduce epidermal whitening. The patch contains a fluorocarbon “that is very good at dissolving gas, and it is already widely used in medicine,” he said. When applied, “it almost instantaneously takes the whitening away; you don’t have to wait the 20 minutes to do your second pass.”

A different technology designed to speed up tattoo removal is the Resonic Rapid Acoustic Pulse device (marketed as Resonic, from Allergan Aesthetics), which is cleared by the FDA for use as an accessory to the 1064 nm Q-switched laser for black tattoo removal in patients with skin types I-III. “This uses acoustic pulses of sound waves; they’re rapid and powerful,” Dr. Ibrahimi said. “They can clear those cavitation bubbles much like the PFD patches do. It’s also thought that they further disperse the tattoo ink particles by supplementing the laser energy as well. It is also purported to alter the body’s healing response, or immune response, which is important in tattoo clearing.”

Dr. Ibrahimi disclosed that he is a member of the Advisory Board for Accure Acne, AbbVie (which owns Allergan), Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.

SAN DIEGO – When picosecond lasers hit the market about 10 years ago, they became a game-changer for tattoo removal, boasting the delivery of energy that is about threefold faster than with nanosecond lasers.

However, picosecond lasers are far from perfect even in the hands of the most experienced clinicians, according to Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford. “They have been very difficult to build from an engineering perspective,” he said at the annual Masters of Aesthetics Symposium. It took a long time for these lasers to come to the market, and they are still fairly expensive and require a lot of maintenance, he noted. In addition, “they are also not quite as ‘picosecond’ as they need to be. I think there is definitely room to improve, but this is the gold standard.”

Today, most clinicians use Q-switched nanosecond and picosecond lasers for tattoo removal, though appropriate wavelengths need to be selected based on the tattoo ink color. Tattoo ink particles average about 0.1 mcm in size, and the thermal relaxation size works out to be less than 10 nanoseconds, with shorter pulses better at capturing the ink particles that are smaller than average.

Lance Sitton Photography/Thinkstock

Black is the most common tattoo color dermatologists treat. “For that, you can typically use a 1064, which has the highest absorption, but you can also use many of the other wavelengths,” he said. “Other colors are less common, followed by red, for which you would use a 532-nm wavelength.”

Dr. Ibrahimi underscored the importance of setting realistic expectations during consults with patients seeking options for tattoo removal. Even with picosecond laser technology, many treatments are typically required and “a good patient consultation is key to setting proper expectations,” he said. “If you promise someone results in 4 to 5 treatments like many of the device companies will say you can achieve, you’re going to have a large group of patients who are disappointed.”

The clinical endpoint to strive for during tattoo removal is whitening of the ink, which typically fades about 20 minutes after treatment. That whitening corresponds to cavitation, or the production of gas vacuoles in the cells that were holding the ink. This discovery led to a technique intended to enhance tattoo removal. In 2012, R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and colleagues published results of a study that compared a single Q-switched laser treatment pass with four treatment passes separated by 20 minutes. After treating 18 tattoos in 12 adults, they found that the technique, known as the “R20” method, was more effective than a single-pass treatment (P < .01).

“Subsequent to this, there has been conflicting data on whether this is truly effective or not,” said Dr. Ibrahimi, who is also on the board of directors for the American Society for Dermatologic Surgery and the American Society for Laser Medicine and Surgery. “Most of us agree that one additional pass would be helpful, but when you’re doing this in the private practice setting, it’s often challenging because patients aren’t necessarily willing to pay more for more than just one pass for their tattoo removal.”

Another recent advance is use of a topical square silicone patch infused with perfluorodecalin (PFD) for use during tattoo removal, which has been shown to reduce epidermal whitening. The patch contains a fluorocarbon “that is very good at dissolving gas, and it is already widely used in medicine,” he said. When applied, “it almost instantaneously takes the whitening away; you don’t have to wait the 20 minutes to do your second pass.”

A different technology designed to speed up tattoo removal is the Resonic Rapid Acoustic Pulse device (marketed as Resonic, from Allergan Aesthetics), which is cleared by the FDA for use as an accessory to the 1064 nm Q-switched laser for black tattoo removal in patients with skin types I-III. “This uses acoustic pulses of sound waves; they’re rapid and powerful,” Dr. Ibrahimi said. “They can clear those cavitation bubbles much like the PFD patches do. It’s also thought that they further disperse the tattoo ink particles by supplementing the laser energy as well. It is also purported to alter the body’s healing response, or immune response, which is important in tattoo clearing.”

Dr. Ibrahimi disclosed that he is a member of the Advisory Board for Accure Acne, AbbVie (which owns Allergan), Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.

SAN DIEGO – When picosecond lasers hit the market about 10 years ago, they became a game-changer for tattoo removal, boasting the delivery of energy that is about threefold faster than with nanosecond lasers.

However, picosecond lasers are far from perfect even in the hands of the most experienced clinicians, according to Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford. “They have been very difficult to build from an engineering perspective,” he said at the annual Masters of Aesthetics Symposium. It took a long time for these lasers to come to the market, and they are still fairly expensive and require a lot of maintenance, he noted. In addition, “they are also not quite as ‘picosecond’ as they need to be. I think there is definitely room to improve, but this is the gold standard.”

Today, most clinicians use Q-switched nanosecond and picosecond lasers for tattoo removal, though appropriate wavelengths need to be selected based on the tattoo ink color. Tattoo ink particles average about 0.1 mcm in size, and the thermal relaxation size works out to be less than 10 nanoseconds, with shorter pulses better at capturing the ink particles that are smaller than average.

Lance Sitton Photography/Thinkstock

Black is the most common tattoo color dermatologists treat. “For that, you can typically use a 1064, which has the highest absorption, but you can also use many of the other wavelengths,” he said. “Other colors are less common, followed by red, for which you would use a 532-nm wavelength.”

Dr. Ibrahimi underscored the importance of setting realistic expectations during consults with patients seeking options for tattoo removal. Even with picosecond laser technology, many treatments are typically required and “a good patient consultation is key to setting proper expectations,” he said. “If you promise someone results in 4 to 5 treatments like many of the device companies will say you can achieve, you’re going to have a large group of patients who are disappointed.”

The clinical endpoint to strive for during tattoo removal is whitening of the ink, which typically fades about 20 minutes after treatment. That whitening corresponds to cavitation, or the production of gas vacuoles in the cells that were holding the ink. This discovery led to a technique intended to enhance tattoo removal. In 2012, R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and colleagues published results of a study that compared a single Q-switched laser treatment pass with four treatment passes separated by 20 minutes. After treating 18 tattoos in 12 adults, they found that the technique, known as the “R20” method, was more effective than a single-pass treatment (P < .01).

“Subsequent to this, there has been conflicting data on whether this is truly effective or not,” said Dr. Ibrahimi, who is also on the board of directors for the American Society for Dermatologic Surgery and the American Society for Laser Medicine and Surgery. “Most of us agree that one additional pass would be helpful, but when you’re doing this in the private practice setting, it’s often challenging because patients aren’t necessarily willing to pay more for more than just one pass for their tattoo removal.”

Another recent advance is use of a topical square silicone patch infused with perfluorodecalin (PFD) for use during tattoo removal, which has been shown to reduce epidermal whitening. The patch contains a fluorocarbon “that is very good at dissolving gas, and it is already widely used in medicine,” he said. When applied, “it almost instantaneously takes the whitening away; you don’t have to wait the 20 minutes to do your second pass.”

A different technology designed to speed up tattoo removal is the Resonic Rapid Acoustic Pulse device (marketed as Resonic, from Allergan Aesthetics), which is cleared by the FDA for use as an accessory to the 1064 nm Q-switched laser for black tattoo removal in patients with skin types I-III. “This uses acoustic pulses of sound waves; they’re rapid and powerful,” Dr. Ibrahimi said. “They can clear those cavitation bubbles much like the PFD patches do. It’s also thought that they further disperse the tattoo ink particles by supplementing the laser energy as well. It is also purported to alter the body’s healing response, or immune response, which is important in tattoo clearing.”

Dr. Ibrahimi disclosed that he is a member of the Advisory Board for Accure Acne, AbbVie (which owns Allergan), Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.

SAN DIEGO – When patients ask if collagen supplements can benefit their skin, what should you tell them?

According to Ava Shamban, MD, a dermatologist who practices in Santa Monica, Calif., limited data exist to suggest that consuming collagen-dense foods can directly benefit skin or joint health. And in her opinion, more research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation.

“Collagen is the most abundant protein in the skin; it is found only in animal flesh like meat and fish that contain connective tissue,” she said at the annual Masters of Aesthetics Symposium. “We produce less collagen as we age. External factors can slow down our collagen production, including smoking, sun exposure, lack of sleep/exercise, and alcohol consumption.”

Though human studies are lacking, some trials have found that collagen supplements may improve skin hydration and elasticity. “Maybe there’s some benefit, but the digestive process breaks collagen down into amino acids, so I don’t buy it,” she said.

At the meeting, Dr. Shamban discussed other topics related to the effect of supplements and nutrition on the skin:

Can Nutrafol reverse permanent hair loss? “It definitely doesn’t do that,” she said. “Can it help regrow hair? Perhaps.” Nutrafol is an over-the-counter supplement that aims to relieve moderate hair thinning or strengthen hair to prevent breakage, and is physician-formulated with medical-grade ingredients that target root causes of thinning such as stress, lifestyle, hormones, and nutrition.

As for biotin, “we now know that high levels of biotin can actually cause hair loss,” she said. “If you have advanced hair loss, supplements may not work for you. There is no hair regrowth supplement that can bring back a dead hair follicle. Can it help a miniaturized hair follicle? Maybe. Platelet-rich plasma injections have been shown to stimulate hair growth, but only if the follicle is miniaturized, not if it’s totally gone.”

How does the human microbiome affect skin? In a review of sequencing surveys of healthy adults, “the composition of microbial communities was found to be primarily dependent on the physiology of the skin site, with changes in the relative abundance of bacterial taxa associated with moist, dry, and sebaceous environments,” the authors reported . “The microbiome is the genetic material of all the microbes that live inside the body, including bacteria, fungi, protozoa, and viruses,” Dr. Shamban said. “The more diverse the microbiota is, the healthier it’s considered. That diversity is enriched through a diet full of various vegetables and fruits.”

Nearly all adults are colonized with Cutibacterium acnes (formerly Propionibacterium acnes), but only a minority have acne, which highlights the importance of studying diseases in the broader context of host genetics, immune or barrier defects, the microbiome, and the environment, she added. For example, the decreased diversity of the skin microbiome in people with atopic dermatitis has been linked to a reduction in environmental biodiversity in the areas surrounding their homes.

Do adaptogens have a role in skin care? Adaptogens such as ashwagandha, elderberry, ginseng, licorice root, neem, moringa, and reishi mushrooms have been used in Chinese and Ayurvedic medicine for centuries and are purported to promote adaptability, resilience, and survival of living organisms in stress. They appear to affect the neuroendocrine immune system and at low doses may function as mild stress mimetics.

“The idea is that combining adaptogens into skin care can reinforce and support the skin’s resistance against stressors that can accelerate visible signs of aging,” said Dr. Shamban. “They share some similarities with antioxidants in that their main purpose is to protect the body from external stressors such as UV rays, oxidation, and pollution.” More studies should be conducted to verify effectiveness, she said, “but Eastern practices that have incorporated it for centuries shouldn’t be fully dismissed. Most doctors believe adaptogens are safe, but how they interact with the mechanics of the body’s stress response system remains a mystery.”

Embrace the consumption of micronutrients. Inspired by work from dermatologist Zoe Diana Draelos, MD, Dr. Shamban advises patients to eat a “rainbow of different colored foods” every day, especially those rich in vitamins A, C, and E. Green foods are generally rich in vitamin E, brown foods are rich in trace minerals, and blue/purple foods are rich in antioxidants. “It’s always best to get nutrients from a rich, healthy diet, but sometimes our skin requires extra help,” she said.

A randomized, placebo-controlled, double-blind study by French researchers, which showed that skin is prone to seasonal changes during the winter, particularly in exposed areas, also looked at whether a daily micronutrient supplement with ingredients that included green tea extract, blackcurrant seed oil, and magnesium, had an impact on the negative effects of winter weather on the skin. “The data indicate that oral micronutrient supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin,” she said.

Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – When patients ask if collagen supplements can benefit their skin, what should you tell them?

According to Ava Shamban, MD, a dermatologist who practices in Santa Monica, Calif., limited data exist to suggest that consuming collagen-dense foods can directly benefit skin or joint health. And in her opinion, more research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation.

“Collagen is the most abundant protein in the skin; it is found only in animal flesh like meat and fish that contain connective tissue,” she said at the annual Masters of Aesthetics Symposium. “We produce less collagen as we age. External factors can slow down our collagen production, including smoking, sun exposure, lack of sleep/exercise, and alcohol consumption.”

Though human studies are lacking, some trials have found that collagen supplements may improve skin hydration and elasticity. “Maybe there’s some benefit, but the digestive process breaks collagen down into amino acids, so I don’t buy it,” she said.

At the meeting, Dr. Shamban discussed other topics related to the effect of supplements and nutrition on the skin:

Can Nutrafol reverse permanent hair loss? “It definitely doesn’t do that,” she said. “Can it help regrow hair? Perhaps.” Nutrafol is an over-the-counter supplement that aims to relieve moderate hair thinning or strengthen hair to prevent breakage, and is physician-formulated with medical-grade ingredients that target root causes of thinning such as stress, lifestyle, hormones, and nutrition.

As for biotin, “we now know that high levels of biotin can actually cause hair loss,” she said. “If you have advanced hair loss, supplements may not work for you. There is no hair regrowth supplement that can bring back a dead hair follicle. Can it help a miniaturized hair follicle? Maybe. Platelet-rich plasma injections have been shown to stimulate hair growth, but only if the follicle is miniaturized, not if it’s totally gone.”

How does the human microbiome affect skin? In a review of sequencing surveys of healthy adults, “the composition of microbial communities was found to be primarily dependent on the physiology of the skin site, with changes in the relative abundance of bacterial taxa associated with moist, dry, and sebaceous environments,” the authors reported . “The microbiome is the genetic material of all the microbes that live inside the body, including bacteria, fungi, protozoa, and viruses,” Dr. Shamban said. “The more diverse the microbiota is, the healthier it’s considered. That diversity is enriched through a diet full of various vegetables and fruits.”

Nearly all adults are colonized with Cutibacterium acnes (formerly Propionibacterium acnes), but only a minority have acne, which highlights the importance of studying diseases in the broader context of host genetics, immune or barrier defects, the microbiome, and the environment, she added. For example, the decreased diversity of the skin microbiome in people with atopic dermatitis has been linked to a reduction in environmental biodiversity in the areas surrounding their homes.

Do adaptogens have a role in skin care? Adaptogens such as ashwagandha, elderberry, ginseng, licorice root, neem, moringa, and reishi mushrooms have been used in Chinese and Ayurvedic medicine for centuries and are purported to promote adaptability, resilience, and survival of living organisms in stress. They appear to affect the neuroendocrine immune system and at low doses may function as mild stress mimetics.

“The idea is that combining adaptogens into skin care can reinforce and support the skin’s resistance against stressors that can accelerate visible signs of aging,” said Dr. Shamban. “They share some similarities with antioxidants in that their main purpose is to protect the body from external stressors such as UV rays, oxidation, and pollution.” More studies should be conducted to verify effectiveness, she said, “but Eastern practices that have incorporated it for centuries shouldn’t be fully dismissed. Most doctors believe adaptogens are safe, but how they interact with the mechanics of the body’s stress response system remains a mystery.”

Embrace the consumption of micronutrients. Inspired by work from dermatologist Zoe Diana Draelos, MD, Dr. Shamban advises patients to eat a “rainbow of different colored foods” every day, especially those rich in vitamins A, C, and E. Green foods are generally rich in vitamin E, brown foods are rich in trace minerals, and blue/purple foods are rich in antioxidants. “It’s always best to get nutrients from a rich, healthy diet, but sometimes our skin requires extra help,” she said.

A randomized, placebo-controlled, double-blind study by French researchers, which showed that skin is prone to seasonal changes during the winter, particularly in exposed areas, also looked at whether a daily micronutrient supplement with ingredients that included green tea extract, blackcurrant seed oil, and magnesium, had an impact on the negative effects of winter weather on the skin. “The data indicate that oral micronutrient supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin,” she said.

Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – When patients ask if collagen supplements can benefit their skin, what should you tell them?

According to Ava Shamban, MD, a dermatologist who practices in Santa Monica, Calif., limited data exist to suggest that consuming collagen-dense foods can directly benefit skin or joint health. And in her opinion, more research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation.

“Collagen is the most abundant protein in the skin; it is found only in animal flesh like meat and fish that contain connective tissue,” she said at the annual Masters of Aesthetics Symposium. “We produce less collagen as we age. External factors can slow down our collagen production, including smoking, sun exposure, lack of sleep/exercise, and alcohol consumption.”

Though human studies are lacking, some trials have found that collagen supplements may improve skin hydration and elasticity. “Maybe there’s some benefit, but the digestive process breaks collagen down into amino acids, so I don’t buy it,” she said.

At the meeting, Dr. Shamban discussed other topics related to the effect of supplements and nutrition on the skin:

Can Nutrafol reverse permanent hair loss? “It definitely doesn’t do that,” she said. “Can it help regrow hair? Perhaps.” Nutrafol is an over-the-counter supplement that aims to relieve moderate hair thinning or strengthen hair to prevent breakage, and is physician-formulated with medical-grade ingredients that target root causes of thinning such as stress, lifestyle, hormones, and nutrition.

As for biotin, “we now know that high levels of biotin can actually cause hair loss,” she said. “If you have advanced hair loss, supplements may not work for you. There is no hair regrowth supplement that can bring back a dead hair follicle. Can it help a miniaturized hair follicle? Maybe. Platelet-rich plasma injections have been shown to stimulate hair growth, but only if the follicle is miniaturized, not if it’s totally gone.”

How does the human microbiome affect skin? In a review of sequencing surveys of healthy adults, “the composition of microbial communities was found to be primarily dependent on the physiology of the skin site, with changes in the relative abundance of bacterial taxa associated with moist, dry, and sebaceous environments,” the authors reported . “The microbiome is the genetic material of all the microbes that live inside the body, including bacteria, fungi, protozoa, and viruses,” Dr. Shamban said. “The more diverse the microbiota is, the healthier it’s considered. That diversity is enriched through a diet full of various vegetables and fruits.”

Nearly all adults are colonized with Cutibacterium acnes (formerly Propionibacterium acnes), but only a minority have acne, which highlights the importance of studying diseases in the broader context of host genetics, immune or barrier defects, the microbiome, and the environment, she added. For example, the decreased diversity of the skin microbiome in people with atopic dermatitis has been linked to a reduction in environmental biodiversity in the areas surrounding their homes.

Do adaptogens have a role in skin care? Adaptogens such as ashwagandha, elderberry, ginseng, licorice root, neem, moringa, and reishi mushrooms have been used in Chinese and Ayurvedic medicine for centuries and are purported to promote adaptability, resilience, and survival of living organisms in stress. They appear to affect the neuroendocrine immune system and at low doses may function as mild stress mimetics.

“The idea is that combining adaptogens into skin care can reinforce and support the skin’s resistance against stressors that can accelerate visible signs of aging,” said Dr. Shamban. “They share some similarities with antioxidants in that their main purpose is to protect the body from external stressors such as UV rays, oxidation, and pollution.” More studies should be conducted to verify effectiveness, she said, “but Eastern practices that have incorporated it for centuries shouldn’t be fully dismissed. Most doctors believe adaptogens are safe, but how they interact with the mechanics of the body’s stress response system remains a mystery.”

Embrace the consumption of micronutrients. Inspired by work from dermatologist Zoe Diana Draelos, MD, Dr. Shamban advises patients to eat a “rainbow of different colored foods” every day, especially those rich in vitamins A, C, and E. Green foods are generally rich in vitamin E, brown foods are rich in trace minerals, and blue/purple foods are rich in antioxidants. “It’s always best to get nutrients from a rich, healthy diet, but sometimes our skin requires extra help,” she said.

A randomized, placebo-controlled, double-blind study by French researchers, which showed that skin is prone to seasonal changes during the winter, particularly in exposed areas, also looked at whether a daily micronutrient supplement with ingredients that included green tea extract, blackcurrant seed oil, and magnesium, had an impact on the negative effects of winter weather on the skin. “The data indicate that oral micronutrient supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin,” she said.

Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – When Arisa E. Ortiz, MD, meets with patients who seek treatment for melasma, she tells them that while she can make their hyperpigmentation better, no cure-all exists for the condition.

“They need to understand that melasma is going to require long-term maintenance,” Dr. Ortiz, director of laser and cosmetic dermatology at the University of California, San Diego, said at the annual Masters of Aesthetics Symposium.

yuuurin/iStock/Getty Images

Hydroquinone is a mainstay of melasma therapy, but instead of the commonly used 4% formulation, she prefers to use 12% hydroquinone with 6% kojic acid in VersaBase cream. “It’s a high concentration but the VersaBase makes it more tolerable,” she said. “I have patients take a pea-sized amount and mix it in a regular moisturizer. It’s too strong to spot treat, so it goes on the whole face.”

Mindful that chronic hydroquinone use can cause ochronosis (permanent darkening), she has patients alternate with a nonhydroquinone bleaching agent such as lignin peroxidase, oligopeptide, Lytera, Melaplex, 4-n-butylresorcinol, Cysteamine cream, tranexamic acid, or oral antioxidants. In a study sponsored by SkinMedica, investigators conducted a randomized, double-blind, half-face study in females with moderate to severe facial hyperpigmentation to assess the efficacy and tolerability of three new skin brightener formulations containing SMA-432, a prostaglandin E2 inhibitor, compared with 4% hydroquinone. They found that the nonhydroquinone skin formulations were better tolerated and were just as effective as 4% hydroquinone.
 

Chemical peels and laser treatments

Chemical peels are another treatment option for melasma, but Dr. Ortiz prefers glycolic peels over salicylic and other peels, “because there is no downtime,” she said.

As for laser-based approaches, melasma patients respond best to low energy devices such as the 1,927-nm fractional diode laser at a 3.75% density. “This also can increase the skin permeability of topicals, so when you’re combining it with hydroquinone it can be more effective,” she said.

In an observational study of 27 women with refractory melasma, with phototypes II-V, New York City–based dermatologist Arielle Kauvar, MD, combined microdermabrasion with the Q-switched Nd:YAG laser. “The settings she used were very low fluence, so there was no clinical endpoint or no whitening,” said Dr. Ortiz, vice president of the American Society for Laser Medicine and Surgery (ASLMS). Specifically, Dr. Kauvar used the laser at 1.6-2 J/cm² with a 5- or 6-mm spot size immediately following microdermabrasion every 4 weeks; Patients received an average of 2.6 treatments, and were assessed 3-12 months after the last treatment. Study participants were on a standard skin care regimen of a broad spectrum sunscreen, hydroquinone, and tretinoin or vitamin C.

Most of the patients showed at least 50% clearance of melasma 1 month after the first treatment, and 81% showed more than 75% clearance of melasma; remission lasted at least 6 months.

“I personally prefer to use picosecond over Q-switched lasers, because they deliver the energy faster, and you can use a 1,064-nm picosecond laser that is safe in all skin types,” Dr. Ortiz said. “There is minimal downtime, and it doesn’t require anesthesia. You have to consider these things when you’re treating melasma, because this usually requires monthly treatments. If you do something that requires a week of downtime every month, it’s not practical for patients.”

In a study published in 2021, Dr. Ortiz and Tanya Greywal, MD, used three passes of the 1,064-nm Nd:YAG laser to treat melasma in 10 patients with skin types II-V. The device had a 650-microsecond pulse duration, a 6-mm spot size, and an energy mode of 11-14 J/cm². The researchers observed a mean melasma improvement of 26%-50% as early as 3 weeks. “There was no downtime, and no anesthesia was required,” Dr. Ortiz said.

Researchers have discovered a vascular component to melasma, which may have treatment implications. Houston-based dermatologist Paul M. Friedman, MD, and his colleagues used spectrocolorimetry to detect an underlying prominent vascular component in a retrospective review of 11 patients with melasma, with skin types II-IV. They determined that melasma lesions exhibiting subtle or subclinical telangiectatic erythema may be improved by combining vascular-targeted laser therapy with fractional low-powered diode laser therapy.

“So, combining a vascular laser with a 1,927-nm fractional diode laser showed more improvement than with just the diode laser alone,” said Dr. Ortiz, who was not involved with the analysis.

To optimize results following the laser treatment of melasma, she uses one application of clobetasol immediately after the procedure. “This can help reduce swelling and inflammation to decrease the risk of postinflammatory hyperpigmentation,” she said. “You can also use a skin cooling system like Cryomodulation for controlled cooling.”
 

Tranexamic acid and PLE

Another strategy for melasma patients involves oral treatment with extract of Polypodium leucotomos (PLE), a fern from the Polypodiaceae family with antioxidant properties that has been shown to be photoprotective against UVA and UVB radiation. “I explain to my patients that it’s like an internal sunscreen,” Dr. Ortiz said. “It does not replace your external sunscreen, but it adds extra protection.”

In a pilot placebo-controlled study of patients with melasma on their normal regimen of hydroquinone and sunscreen, 40 Asian patients with melasma were randomized to receive either oral PLE supplementation or placebo for 12 weeks. The authors found that PLE significantly improved and accelerated the outcome reached with hydroquinone and sunscreen from about the first month of treatment, compared with placebo.

Dr. Ortiz discussed the role of oral tranexamic acid, an antifibrinolytic, procoagulant agent that is approved by the Food and Drug Administration for the treatment of menorrhagia and to prevent hemorrhage in patients with hemophilia undergoing tooth extractions. “This is a game changer for melasma treatment,” she said, but its use has been limited by the risk for thromboembolism.

In a study of 561 patients with melasma, 90% improved after a median treatment duration of 4 months, and only 7% had side effects, most commonly abdominal bloating and pain. Treatment was discontinued in one patient who developed a deep vein thrombosis, and was diagnosed with familial protein S deficiency.

The daily dosing of tranexamic acid for menorrhagia is 3,900 mg daily, while the dose for treating melasma has ranged from 500 mg to 1,500 mg per day, Dr. Ortiz said. It’s available as a 650-mg tablet in the United States. “I prescribe 325 mg twice a day, but studies have shown that 650 mg once a day is just as effective,” she said.

Prior to prescribing tranexamic acid, Dr. Ortiz does not order labs, but she performs an extensive history of current illness and does not prescribe it in patients with an increased risk of clotting, including people who smoke and those who take oral contraceptives or are on hormone supplementation. Use is also contraindicated in people with a current malignancy, those with a history of stroke or DVT, and those who have any clotting disorder.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is cochair of the Masters of Aesthetics Symposium.

SAN DIEGO – When Arisa E. Ortiz, MD, meets with patients who seek treatment for melasma, she tells them that while she can make their hyperpigmentation better, no cure-all exists for the condition.

“They need to understand that melasma is going to require long-term maintenance,” Dr. Ortiz, director of laser and cosmetic dermatology at the University of California, San Diego, said at the annual Masters of Aesthetics Symposium.

yuuurin/iStock/Getty Images

Hydroquinone is a mainstay of melasma therapy, but instead of the commonly used 4% formulation, she prefers to use 12% hydroquinone with 6% kojic acid in VersaBase cream. “It’s a high concentration but the VersaBase makes it more tolerable,” she said. “I have patients take a pea-sized amount and mix it in a regular moisturizer. It’s too strong to spot treat, so it goes on the whole face.”

Mindful that chronic hydroquinone use can cause ochronosis (permanent darkening), she has patients alternate with a nonhydroquinone bleaching agent such as lignin peroxidase, oligopeptide, Lytera, Melaplex, 4-n-butylresorcinol, Cysteamine cream, tranexamic acid, or oral antioxidants. In a study sponsored by SkinMedica, investigators conducted a randomized, double-blind, half-face study in females with moderate to severe facial hyperpigmentation to assess the efficacy and tolerability of three new skin brightener formulations containing SMA-432, a prostaglandin E2 inhibitor, compared with 4% hydroquinone. They found that the nonhydroquinone skin formulations were better tolerated and were just as effective as 4% hydroquinone.
 

Chemical peels and laser treatments

Chemical peels are another treatment option for melasma, but Dr. Ortiz prefers glycolic peels over salicylic and other peels, “because there is no downtime,” she said.

As for laser-based approaches, melasma patients respond best to low energy devices such as the 1,927-nm fractional diode laser at a 3.75% density. “This also can increase the skin permeability of topicals, so when you’re combining it with hydroquinone it can be more effective,” she said.

In an observational study of 27 women with refractory melasma, with phototypes II-V, New York City–based dermatologist Arielle Kauvar, MD, combined microdermabrasion with the Q-switched Nd:YAG laser. “The settings she used were very low fluence, so there was no clinical endpoint or no whitening,” said Dr. Ortiz, vice president of the American Society for Laser Medicine and Surgery (ASLMS). Specifically, Dr. Kauvar used the laser at 1.6-2 J/cm² with a 5- or 6-mm spot size immediately following microdermabrasion every 4 weeks; Patients received an average of 2.6 treatments, and were assessed 3-12 months after the last treatment. Study participants were on a standard skin care regimen of a broad spectrum sunscreen, hydroquinone, and tretinoin or vitamin C.

Most of the patients showed at least 50% clearance of melasma 1 month after the first treatment, and 81% showed more than 75% clearance of melasma; remission lasted at least 6 months.

“I personally prefer to use picosecond over Q-switched lasers, because they deliver the energy faster, and you can use a 1,064-nm picosecond laser that is safe in all skin types,” Dr. Ortiz said. “There is minimal downtime, and it doesn’t require anesthesia. You have to consider these things when you’re treating melasma, because this usually requires monthly treatments. If you do something that requires a week of downtime every month, it’s not practical for patients.”

In a study published in 2021, Dr. Ortiz and Tanya Greywal, MD, used three passes of the 1,064-nm Nd:YAG laser to treat melasma in 10 patients with skin types II-V. The device had a 650-microsecond pulse duration, a 6-mm spot size, and an energy mode of 11-14 J/cm². The researchers observed a mean melasma improvement of 26%-50% as early as 3 weeks. “There was no downtime, and no anesthesia was required,” Dr. Ortiz said.

Researchers have discovered a vascular component to melasma, which may have treatment implications. Houston-based dermatologist Paul M. Friedman, MD, and his colleagues used spectrocolorimetry to detect an underlying prominent vascular component in a retrospective review of 11 patients with melasma, with skin types II-IV. They determined that melasma lesions exhibiting subtle or subclinical telangiectatic erythema may be improved by combining vascular-targeted laser therapy with fractional low-powered diode laser therapy.

“So, combining a vascular laser with a 1,927-nm fractional diode laser showed more improvement than with just the diode laser alone,” said Dr. Ortiz, who was not involved with the analysis.

To optimize results following the laser treatment of melasma, she uses one application of clobetasol immediately after the procedure. “This can help reduce swelling and inflammation to decrease the risk of postinflammatory hyperpigmentation,” she said. “You can also use a skin cooling system like Cryomodulation for controlled cooling.”
 

Tranexamic acid and PLE

Another strategy for melasma patients involves oral treatment with extract of Polypodium leucotomos (PLE), a fern from the Polypodiaceae family with antioxidant properties that has been shown to be photoprotective against UVA and UVB radiation. “I explain to my patients that it’s like an internal sunscreen,” Dr. Ortiz said. “It does not replace your external sunscreen, but it adds extra protection.”

In a pilot placebo-controlled study of patients with melasma on their normal regimen of hydroquinone and sunscreen, 40 Asian patients with melasma were randomized to receive either oral PLE supplementation or placebo for 12 weeks. The authors found that PLE significantly improved and accelerated the outcome reached with hydroquinone and sunscreen from about the first month of treatment, compared with placebo.

Dr. Ortiz discussed the role of oral tranexamic acid, an antifibrinolytic, procoagulant agent that is approved by the Food and Drug Administration for the treatment of menorrhagia and to prevent hemorrhage in patients with hemophilia undergoing tooth extractions. “This is a game changer for melasma treatment,” she said, but its use has been limited by the risk for thromboembolism.

In a study of 561 patients with melasma, 90% improved after a median treatment duration of 4 months, and only 7% had side effects, most commonly abdominal bloating and pain. Treatment was discontinued in one patient who developed a deep vein thrombosis, and was diagnosed with familial protein S deficiency.

The daily dosing of tranexamic acid for menorrhagia is 3,900 mg daily, while the dose for treating melasma has ranged from 500 mg to 1,500 mg per day, Dr. Ortiz said. It’s available as a 650-mg tablet in the United States. “I prescribe 325 mg twice a day, but studies have shown that 650 mg once a day is just as effective,” she said.

Prior to prescribing tranexamic acid, Dr. Ortiz does not order labs, but she performs an extensive history of current illness and does not prescribe it in patients with an increased risk of clotting, including people who smoke and those who take oral contraceptives or are on hormone supplementation. Use is also contraindicated in people with a current malignancy, those with a history of stroke or DVT, and those who have any clotting disorder.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is cochair of the Masters of Aesthetics Symposium.

SAN DIEGO – When Arisa E. Ortiz, MD, meets with patients who seek treatment for melasma, she tells them that while she can make their hyperpigmentation better, no cure-all exists for the condition.

“They need to understand that melasma is going to require long-term maintenance,” Dr. Ortiz, director of laser and cosmetic dermatology at the University of California, San Diego, said at the annual Masters of Aesthetics Symposium.

yuuurin/iStock/Getty Images

Hydroquinone is a mainstay of melasma therapy, but instead of the commonly used 4% formulation, she prefers to use 12% hydroquinone with 6% kojic acid in VersaBase cream. “It’s a high concentration but the VersaBase makes it more tolerable,” she said. “I have patients take a pea-sized amount and mix it in a regular moisturizer. It’s too strong to spot treat, so it goes on the whole face.”

Mindful that chronic hydroquinone use can cause ochronosis (permanent darkening), she has patients alternate with a nonhydroquinone bleaching agent such as lignin peroxidase, oligopeptide, Lytera, Melaplex, 4-n-butylresorcinol, Cysteamine cream, tranexamic acid, or oral antioxidants. In a study sponsored by SkinMedica, investigators conducted a randomized, double-blind, half-face study in females with moderate to severe facial hyperpigmentation to assess the efficacy and tolerability of three new skin brightener formulations containing SMA-432, a prostaglandin E2 inhibitor, compared with 4% hydroquinone. They found that the nonhydroquinone skin formulations were better tolerated and were just as effective as 4% hydroquinone.
 

Chemical peels and laser treatments

Chemical peels are another treatment option for melasma, but Dr. Ortiz prefers glycolic peels over salicylic and other peels, “because there is no downtime,” she said.

As for laser-based approaches, melasma patients respond best to low energy devices such as the 1,927-nm fractional diode laser at a 3.75% density. “This also can increase the skin permeability of topicals, so when you’re combining it with hydroquinone it can be more effective,” she said.

In an observational study of 27 women with refractory melasma, with phototypes II-V, New York City–based dermatologist Arielle Kauvar, MD, combined microdermabrasion with the Q-switched Nd:YAG laser. “The settings she used were very low fluence, so there was no clinical endpoint or no whitening,” said Dr. Ortiz, vice president of the American Society for Laser Medicine and Surgery (ASLMS). Specifically, Dr. Kauvar used the laser at 1.6-2 J/cm² with a 5- or 6-mm spot size immediately following microdermabrasion every 4 weeks; Patients received an average of 2.6 treatments, and were assessed 3-12 months after the last treatment. Study participants were on a standard skin care regimen of a broad spectrum sunscreen, hydroquinone, and tretinoin or vitamin C.

Most of the patients showed at least 50% clearance of melasma 1 month after the first treatment, and 81% showed more than 75% clearance of melasma; remission lasted at least 6 months.

“I personally prefer to use picosecond over Q-switched lasers, because they deliver the energy faster, and you can use a 1,064-nm picosecond laser that is safe in all skin types,” Dr. Ortiz said. “There is minimal downtime, and it doesn’t require anesthesia. You have to consider these things when you’re treating melasma, because this usually requires monthly treatments. If you do something that requires a week of downtime every month, it’s not practical for patients.”

In a study published in 2021, Dr. Ortiz and Tanya Greywal, MD, used three passes of the 1,064-nm Nd:YAG laser to treat melasma in 10 patients with skin types II-V. The device had a 650-microsecond pulse duration, a 6-mm spot size, and an energy mode of 11-14 J/cm². The researchers observed a mean melasma improvement of 26%-50% as early as 3 weeks. “There was no downtime, and no anesthesia was required,” Dr. Ortiz said.

Researchers have discovered a vascular component to melasma, which may have treatment implications. Houston-based dermatologist Paul M. Friedman, MD, and his colleagues used spectrocolorimetry to detect an underlying prominent vascular component in a retrospective review of 11 patients with melasma, with skin types II-IV. They determined that melasma lesions exhibiting subtle or subclinical telangiectatic erythema may be improved by combining vascular-targeted laser therapy with fractional low-powered diode laser therapy.

“So, combining a vascular laser with a 1,927-nm fractional diode laser showed more improvement than with just the diode laser alone,” said Dr. Ortiz, who was not involved with the analysis.

To optimize results following the laser treatment of melasma, she uses one application of clobetasol immediately after the procedure. “This can help reduce swelling and inflammation to decrease the risk of postinflammatory hyperpigmentation,” she said. “You can also use a skin cooling system like Cryomodulation for controlled cooling.”
 

Tranexamic acid and PLE

Another strategy for melasma patients involves oral treatment with extract of Polypodium leucotomos (PLE), a fern from the Polypodiaceae family with antioxidant properties that has been shown to be photoprotective against UVA and UVB radiation. “I explain to my patients that it’s like an internal sunscreen,” Dr. Ortiz said. “It does not replace your external sunscreen, but it adds extra protection.”

In a pilot placebo-controlled study of patients with melasma on their normal regimen of hydroquinone and sunscreen, 40 Asian patients with melasma were randomized to receive either oral PLE supplementation or placebo for 12 weeks. The authors found that PLE significantly improved and accelerated the outcome reached with hydroquinone and sunscreen from about the first month of treatment, compared with placebo.

Dr. Ortiz discussed the role of oral tranexamic acid, an antifibrinolytic, procoagulant agent that is approved by the Food and Drug Administration for the treatment of menorrhagia and to prevent hemorrhage in patients with hemophilia undergoing tooth extractions. “This is a game changer for melasma treatment,” she said, but its use has been limited by the risk for thromboembolism.

In a study of 561 patients with melasma, 90% improved after a median treatment duration of 4 months, and only 7% had side effects, most commonly abdominal bloating and pain. Treatment was discontinued in one patient who developed a deep vein thrombosis, and was diagnosed with familial protein S deficiency.

The daily dosing of tranexamic acid for menorrhagia is 3,900 mg daily, while the dose for treating melasma has ranged from 500 mg to 1,500 mg per day, Dr. Ortiz said. It’s available as a 650-mg tablet in the United States. “I prescribe 325 mg twice a day, but studies have shown that 650 mg once a day is just as effective,” she said.

Prior to prescribing tranexamic acid, Dr. Ortiz does not order labs, but she performs an extensive history of current illness and does not prescribe it in patients with an increased risk of clotting, including people who smoke and those who take oral contraceptives or are on hormone supplementation. Use is also contraindicated in people with a current malignancy, those with a history of stroke or DVT, and those who have any clotting disorder.

Dr. Ortiz disclosed having financial relationships with several pharmaceutical and device companies. She is cochair of the Masters of Aesthetics Symposium.

SAN DIEGO – While laser procedures, injectables, and chemical peels may be considered the bread and butter of a cosmetic dermatology practice, don’t forget about cosmeceuticals, advised Ava Shamban, MD.

It’s important to provide patients with high-quality products to take home with them and cosmeceuticals contain biologically active ingredients that enhance skin care efficacy, Dr. Shamban, a dermatologist who practices in Santa Monica, Calif., said at the annual Masters of Aesthetics Symposium. “You can do all the lasers, injectables, and peels that you want, but if you’re not giving your patients high-quality products to take home with them, you’re not doing your job,” she commented.

“Look for brands that are formulated and tested for effectiveness,” she added. “In my office, we like to have products that are designed for specific issues to accompany prescription products, everything from rosacea, acne, melasma, and eczema to psoriasis.”

Dr. Shamban, author of the 2011 book, “Heal Your Skin: The Breakthrough Plan for Renewal,” recommends that dermatologists devise a questionnaire for patients asking them to list their skin-related concerns and use the responses to create a list of products for them to use at home. Provide clear instructions on use, including proper layering of products, how often to use them, and the correct amount to apply. “If you’re not going to do this, someone else will,” she said. Next, instruct them that cosmeceuticals must be used routinely to achieve optimal benefit. “Nothing happens overnight, and be wary of anyone that promises you otherwise,” Dr. Shamban said. “Offering cosmeceuticals helps bridge the gap between at-home routines and in-office treatments. If in-office procedures are a marathon, view the consistent use of the right products at home as your training.”

Bill Oxford/E+

During her presentation, she showed a photo of the “beauty bar,” the dedicated space with a counter and shelves for displaying skin care products in her Santa Monica office. “It’s good to set something up like this in your office, even if it’s just a little corner, because it gives it authority,” Dr. Shamban said. “Encourage clients to explore the beauty bar after their appointment with you.” She emphasized the importance of offering a wide range of products to accommodate different lifestyles, budgets, skin types, ages, and specific skin concerns, and training staff about the products. “There is never a one-size-fits-all approach to skincare; it’s all about the individual,” she said. “It’s never about pushing product; it’s always about educating patients.”

Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – While laser procedures, injectables, and chemical peels may be considered the bread and butter of a cosmetic dermatology practice, don’t forget about cosmeceuticals, advised Ava Shamban, MD.

It’s important to provide patients with high-quality products to take home with them and cosmeceuticals contain biologically active ingredients that enhance skin care efficacy, Dr. Shamban, a dermatologist who practices in Santa Monica, Calif., said at the annual Masters of Aesthetics Symposium. “You can do all the lasers, injectables, and peels that you want, but if you’re not giving your patients high-quality products to take home with them, you’re not doing your job,” she commented.

“Look for brands that are formulated and tested for effectiveness,” she added. “In my office, we like to have products that are designed for specific issues to accompany prescription products, everything from rosacea, acne, melasma, and eczema to psoriasis.”

Dr. Shamban, author of the 2011 book, “Heal Your Skin: The Breakthrough Plan for Renewal,” recommends that dermatologists devise a questionnaire for patients asking them to list their skin-related concerns and use the responses to create a list of products for them to use at home. Provide clear instructions on use, including proper layering of products, how often to use them, and the correct amount to apply. “If you’re not going to do this, someone else will,” she said. Next, instruct them that cosmeceuticals must be used routinely to achieve optimal benefit. “Nothing happens overnight, and be wary of anyone that promises you otherwise,” Dr. Shamban said. “Offering cosmeceuticals helps bridge the gap between at-home routines and in-office treatments. If in-office procedures are a marathon, view the consistent use of the right products at home as your training.”

Bill Oxford/E+

During her presentation, she showed a photo of the “beauty bar,” the dedicated space with a counter and shelves for displaying skin care products in her Santa Monica office. “It’s good to set something up like this in your office, even if it’s just a little corner, because it gives it authority,” Dr. Shamban said. “Encourage clients to explore the beauty bar after their appointment with you.” She emphasized the importance of offering a wide range of products to accommodate different lifestyles, budgets, skin types, ages, and specific skin concerns, and training staff about the products. “There is never a one-size-fits-all approach to skincare; it’s all about the individual,” she said. “It’s never about pushing product; it’s always about educating patients.”

Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – While laser procedures, injectables, and chemical peels may be considered the bread and butter of a cosmetic dermatology practice, don’t forget about cosmeceuticals, advised Ava Shamban, MD.

It’s important to provide patients with high-quality products to take home with them and cosmeceuticals contain biologically active ingredients that enhance skin care efficacy, Dr. Shamban, a dermatologist who practices in Santa Monica, Calif., said at the annual Masters of Aesthetics Symposium. “You can do all the lasers, injectables, and peels that you want, but if you’re not giving your patients high-quality products to take home with them, you’re not doing your job,” she commented.

“Look for brands that are formulated and tested for effectiveness,” she added. “In my office, we like to have products that are designed for specific issues to accompany prescription products, everything from rosacea, acne, melasma, and eczema to psoriasis.”

Dr. Shamban, author of the 2011 book, “Heal Your Skin: The Breakthrough Plan for Renewal,” recommends that dermatologists devise a questionnaire for patients asking them to list their skin-related concerns and use the responses to create a list of products for them to use at home. Provide clear instructions on use, including proper layering of products, how often to use them, and the correct amount to apply. “If you’re not going to do this, someone else will,” she said. Next, instruct them that cosmeceuticals must be used routinely to achieve optimal benefit. “Nothing happens overnight, and be wary of anyone that promises you otherwise,” Dr. Shamban said. “Offering cosmeceuticals helps bridge the gap between at-home routines and in-office treatments. If in-office procedures are a marathon, view the consistent use of the right products at home as your training.”

Bill Oxford/E+

During her presentation, she showed a photo of the “beauty bar,” the dedicated space with a counter and shelves for displaying skin care products in her Santa Monica office. “It’s good to set something up like this in your office, even if it’s just a little corner, because it gives it authority,” Dr. Shamban said. “Encourage clients to explore the beauty bar after their appointment with you.” She emphasized the importance of offering a wide range of products to accommodate different lifestyles, budgets, skin types, ages, and specific skin concerns, and training staff about the products. “There is never a one-size-fits-all approach to skincare; it’s all about the individual,” she said. “It’s never about pushing product; it’s always about educating patients.”

Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – If approved, a novel topical gel that combines an antibiotic, an antibacterial, and a retinoid would mark an important advance for many patients with moderate-to-severe acne, according to Lawrence F. Eichenfield, MD.

The product, known as IDP-126 and being developed by Ortho Dermatologics, is a fixed dose triple combination of clindamycin 1.2% plus benzoyl peroxide 3.1% and adapalene 0.15% being evaluated in patients nine years of age and older. According to a 2021 press release from the company, results from a second 12-week pivotal phase 3 trial showed a treatment success of 50.5% and 20.5% for IDP-126 and its vehicle, respectively, along with significant changes from baseline in inflammatory lesion count and non-inflammatory lesion count.

olavs/Thinkstock

More recently, researchers led by Linda Stein Gold, MD, conducted a 12-week multicenter, randomized, double-blind study of IDP-126 in 741 children, adolescents, and adults with moderate to severe acne. They reported 52.5% of patients treated with IDP-126 gel achieved treatment success by week 12, with over 70% reduction in inflammatory and noninflammatory lesions.

“This will be interesting to follow as it moves along,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, said at the annual Masters of Aesthetics Symposium in a presentation on the newest topical acne treatments.

“If approved, we probably will be able to decrease our need for systemic therapies in some individuals,” he said. “It’s something that may become important in practices that mix and match between medical and procedural or surgical approaches to acne.”

Dr. Eichenfield highlighted other products for the topical treatment of acne:

• Trifarotene cream 0.005% (Aklief). In 2019, Food and Drug Administration approval made trifarotene cream the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients age 9 and older and has been studied in acne of the face, chest, and back.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “Many of the new acne products come with a background of vehicle delivery systems that minimize the concentration gradient, so it decreases irritation,” said Dr. Eichenfield, one of the authors of a 2021 review article on the management of acne vulgaris in JAMA. “This has very good efficacy without the traditional irritation of other tazarotene products,” Dr. Eichenfield said.
• Minocycline 4% topical foam (Amzeeq). The 2019 U.S. approval marked the first and so far only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “It’s generally well tolerated.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor is approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It is safe for use in men, has been studied on the face and trunk, and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” Dr. Eichenfield said.
• Micro-encapsulated benzoyl peroxide 3% and tretinoin 0.1% cream (Twyneo). This is a once-daily fixed-dose combination of tretinoin and benzoyl peroxide indicated for the treatment of acne vulgaris in patients age 9 and older. According to a press release from Sol-Gel, the manufacturer, silica (silicon dioxide) core shell structures separate micro-encapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the two active ingredients in the cream.

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics.

SAN DIEGO – If approved, a novel topical gel that combines an antibiotic, an antibacterial, and a retinoid would mark an important advance for many patients with moderate-to-severe acne, according to Lawrence F. Eichenfield, MD.

The product, known as IDP-126 and being developed by Ortho Dermatologics, is a fixed dose triple combination of clindamycin 1.2% plus benzoyl peroxide 3.1% and adapalene 0.15% being evaluated in patients nine years of age and older. According to a 2021 press release from the company, results from a second 12-week pivotal phase 3 trial showed a treatment success of 50.5% and 20.5% for IDP-126 and its vehicle, respectively, along with significant changes from baseline in inflammatory lesion count and non-inflammatory lesion count.

olavs/Thinkstock

More recently, researchers led by Linda Stein Gold, MD, conducted a 12-week multicenter, randomized, double-blind study of IDP-126 in 741 children, adolescents, and adults with moderate to severe acne. They reported 52.5% of patients treated with IDP-126 gel achieved treatment success by week 12, with over 70% reduction in inflammatory and noninflammatory lesions.

“This will be interesting to follow as it moves along,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, said at the annual Masters of Aesthetics Symposium in a presentation on the newest topical acne treatments.

“If approved, we probably will be able to decrease our need for systemic therapies in some individuals,” he said. “It’s something that may become important in practices that mix and match between medical and procedural or surgical approaches to acne.”

Dr. Eichenfield highlighted other products for the topical treatment of acne:

• Trifarotene cream 0.005% (Aklief). In 2019, Food and Drug Administration approval made trifarotene cream the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients age 9 and older and has been studied in acne of the face, chest, and back.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “Many of the new acne products come with a background of vehicle delivery systems that minimize the concentration gradient, so it decreases irritation,” said Dr. Eichenfield, one of the authors of a 2021 review article on the management of acne vulgaris in JAMA. “This has very good efficacy without the traditional irritation of other tazarotene products,” Dr. Eichenfield said.
• Minocycline 4% topical foam (Amzeeq). The 2019 U.S. approval marked the first and so far only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “It’s generally well tolerated.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor is approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It is safe for use in men, has been studied on the face and trunk, and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” Dr. Eichenfield said.
• Micro-encapsulated benzoyl peroxide 3% and tretinoin 0.1% cream (Twyneo). This is a once-daily fixed-dose combination of tretinoin and benzoyl peroxide indicated for the treatment of acne vulgaris in patients age 9 and older. According to a press release from Sol-Gel, the manufacturer, silica (silicon dioxide) core shell structures separate micro-encapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the two active ingredients in the cream.

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics.

SAN DIEGO – If approved, a novel topical gel that combines an antibiotic, an antibacterial, and a retinoid would mark an important advance for many patients with moderate-to-severe acne, according to Lawrence F. Eichenfield, MD.

The product, known as IDP-126 and being developed by Ortho Dermatologics, is a fixed dose triple combination of clindamycin 1.2% plus benzoyl peroxide 3.1% and adapalene 0.15% being evaluated in patients nine years of age and older. According to a 2021 press release from the company, results from a second 12-week pivotal phase 3 trial showed a treatment success of 50.5% and 20.5% for IDP-126 and its vehicle, respectively, along with significant changes from baseline in inflammatory lesion count and non-inflammatory lesion count.

olavs/Thinkstock

More recently, researchers led by Linda Stein Gold, MD, conducted a 12-week multicenter, randomized, double-blind study of IDP-126 in 741 children, adolescents, and adults with moderate to severe acne. They reported 52.5% of patients treated with IDP-126 gel achieved treatment success by week 12, with over 70% reduction in inflammatory and noninflammatory lesions.

“This will be interesting to follow as it moves along,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, said at the annual Masters of Aesthetics Symposium in a presentation on the newest topical acne treatments.

“If approved, we probably will be able to decrease our need for systemic therapies in some individuals,” he said. “It’s something that may become important in practices that mix and match between medical and procedural or surgical approaches to acne.”

Dr. Eichenfield highlighted other products for the topical treatment of acne:

• Trifarotene cream 0.005% (Aklief). In 2019, Food and Drug Administration approval made trifarotene cream the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients age 9 and older and has been studied in acne of the face, chest, and back.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “Many of the new acne products come with a background of vehicle delivery systems that minimize the concentration gradient, so it decreases irritation,” said Dr. Eichenfield, one of the authors of a 2021 review article on the management of acne vulgaris in JAMA. “This has very good efficacy without the traditional irritation of other tazarotene products,” Dr. Eichenfield said.
• Minocycline 4% topical foam (Amzeeq). The 2019 U.S. approval marked the first and so far only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “It’s generally well tolerated.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor is approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It is safe for use in men, has been studied on the face and trunk, and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” Dr. Eichenfield said.
• Micro-encapsulated benzoyl peroxide 3% and tretinoin 0.1% cream (Twyneo). This is a once-daily fixed-dose combination of tretinoin and benzoyl peroxide indicated for the treatment of acne vulgaris in patients age 9 and older. According to a press release from Sol-Gel, the manufacturer, silica (silicon dioxide) core shell structures separate micro-encapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the two active ingredients in the cream.

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics.

LAS VEGAS – Vitiligo affects individuals of all ages, and “the social impact is huge,” David Rosmarin, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.

SolStock/Moment/Getty Images

Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.

The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.

Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.

Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.

In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.

Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.

In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.

In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.

Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.

Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.

JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.

Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.

An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.

Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.

Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.

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

LAS VEGAS – Vitiligo affects individuals of all ages, and “the social impact is huge,” David Rosmarin, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.

SolStock/Moment/Getty Images

Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.

The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.

Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.

Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.

In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.

Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.

In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.

In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.

Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.

Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.

JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.

Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.

An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.

Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.

Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.

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

LAS VEGAS – Vitiligo affects individuals of all ages, and “the social impact is huge,” David Rosmarin, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.

SolStock/Moment/Getty Images

Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.

The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.

Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.

Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.

In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.

Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.

In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.

In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.

Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.

Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.

JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.

Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.

An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.

Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.

Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.

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

LAS VEGAS – Although the range of oral psoriasis therapies continues to expand, “topical therapy is still the cornerstone of the treatment of psoriasis,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.

petekarici/Getty Images

Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.

The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.

In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.

Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
 

Get proactive to maintain results

With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.

Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,

She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.

What’s new and approved

Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.

Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.

In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.

Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.

Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.

Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.

Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.

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

LAS VEGAS – Although the range of oral psoriasis therapies continues to expand, “topical therapy is still the cornerstone of the treatment of psoriasis,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.

petekarici/Getty Images

Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.

The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.

In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.

Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
 

Get proactive to maintain results

With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.

Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,

She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.

What’s new and approved

Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.

Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.

In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.

Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.

Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.

Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.

Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.

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

LAS VEGAS – Although the range of oral psoriasis therapies continues to expand, “topical therapy is still the cornerstone of the treatment of psoriasis,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.

petekarici/Getty Images

Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.

The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.

In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.

Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
 

Get proactive to maintain results

With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.

Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,

She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.

What’s new and approved

Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.

Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.

In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.

Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.

Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.

Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.

Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.

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

SAN DIEGO – In the clinical experience of Jeremy B. Green, MD, men typically require a higher dose of facial neuromodulators for nonsurgical wrinkle reduction compared with women because of anatomical differences.

“Men generally have larger facial muscle mass,” Dr. Green, a dermatologist in Coral Gables, Fla., said at the annual Masters of Aesthetics Symposium. “We need a higher dose to treat them, or they will not be happy. In general, I try to increase the dose by about 50% for my male patients.”

Two early trials of dose adjustments support this practice, he said. In one, 80 men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (Botox) in the glabellar area. The researchers found that the 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose.

In a subsequent study, researchers administered botulinum toxin type A (Dysport) 0.5 to 0.7 mL for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation at several time points up to 150 days post treatment. The median duration of effect was 109 days vs. 0 days for placebo in the blinded evaluator evaluation and 107 days vs. 0 for placebo in the patient self-evaluation.

Most injection algorithms for treating the glabella rely on a 5- or 7-point injection technique, but in 2021, researchers led by Sebastian Cotofana, MD, PhD, of the department of clinical anatomy at Mayo Clinic, Rochester, Minn., reported results from a study of the efficacy and safety of a refined 3-point injection technique targeting horizontal and vertical lines to prevent brow ptosis.

“Prior to this study Sebastian asked me, ‘Why do you guys always inject the body of the muscle?’ ” Dr. Green said. “‘If you inject the origin of the muscle on bone, you could more effectively wipe out the entire muscle’s movement. You’re going to get a better result at a lower dose, so let’s study this.’”

The injection technique involves targeting the midline level of the connecting line between left and right medial canthal ligaments with a 90-degree injection angle with bone contact, as well as the medial and inferior margin of eyebrows with a 45-degree injection angle in relation to midline with frontal bone contact. These three points are located inferior to the traditional (on-label) glabellar frown line injections used to treat the frontalis and the brow depressors.

The researchers used the 5-point glabellar line severity scale to evaluate the time of effect onset and the injection-related outcome 120 days after the treatment in 27 men and 78 women. They found that the onset of the neuromodulator effect occurred in an average of 3.5 days, and no adverse events such as eyebrow ptosis, upper eyelid ptosis, medial eyebrow ptosis, and lateral frontalis hyperactivity occurred during the study period.

“If you inject the origin of these muscles, you can get a brow lift with this technique by avoiding frontalis altogether,” Dr. Green said. “The caveat is, it’s so great at lifting the brows that if you treat the forehead, you may create a midline horizontal ‘shelf’ like I’ve never seen before, where the eyebrows elevate into an immobile superior frontalis.”

To avoid this when treating the forehead as well, he’s learned to split the dose of neuromodulator. “If I was injecting 5 units in the procerus before, I’ll do 2.5 units on nasal bone at the insertion of the muscle and then 2.5 units higher up in the traditional midline procerus injection site,” Dr. Green said.

“Same with the corrugators,” he continued. “Then, remember to inject more superficially in the lateral part, the tail of the corrugators, because the tail of the corrugators is inserting into the undersurface of the dermis. That’s why you see that skin puckering in the lateral brows when people frown. You’re pretty safe to chase that laterally if the brow’s already flat as in men, but I caution you [not] to do that in women, because you may flatten the brow.”

Dr. Green said that he is aware of two cases of lid ptosis from the 3-point technique, one of which happened to him.

“When you’re on the bone with your thumb you can feel that liquid traveling along the bone,” he said. “It can travel all the way to the midline pupil where the levator palpebrae superioris muscle is. I now don’t come in contact with bone with my corrugator origin injections, but rather float the needle a couple of millimeters off bone (in muscle) to hopefully prevent that from happening. Alternatively, some people will compress the brow along frontal bone lateral to that corrugator injection site while they’re injecting to prevent backflow of the neuromodulator.”

Dr. Green reported having received research funding and/or consulting fees from many device and pharmaceutical companies.

SAN DIEGO – In the clinical experience of Jeremy B. Green, MD, men typically require a higher dose of facial neuromodulators for nonsurgical wrinkle reduction compared with women because of anatomical differences.

“Men generally have larger facial muscle mass,” Dr. Green, a dermatologist in Coral Gables, Fla., said at the annual Masters of Aesthetics Symposium. “We need a higher dose to treat them, or they will not be happy. In general, I try to increase the dose by about 50% for my male patients.”

Two early trials of dose adjustments support this practice, he said. In one, 80 men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (Botox) in the glabellar area. The researchers found that the 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose.

In a subsequent study, researchers administered botulinum toxin type A (Dysport) 0.5 to 0.7 mL for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation at several time points up to 150 days post treatment. The median duration of effect was 109 days vs. 0 days for placebo in the blinded evaluator evaluation and 107 days vs. 0 for placebo in the patient self-evaluation.

Most injection algorithms for treating the glabella rely on a 5- or 7-point injection technique, but in 2021, researchers led by Sebastian Cotofana, MD, PhD, of the department of clinical anatomy at Mayo Clinic, Rochester, Minn., reported results from a study of the efficacy and safety of a refined 3-point injection technique targeting horizontal and vertical lines to prevent brow ptosis.

“Prior to this study Sebastian asked me, ‘Why do you guys always inject the body of the muscle?’ ” Dr. Green said. “‘If you inject the origin of the muscle on bone, you could more effectively wipe out the entire muscle’s movement. You’re going to get a better result at a lower dose, so let’s study this.’”

The injection technique involves targeting the midline level of the connecting line between left and right medial canthal ligaments with a 90-degree injection angle with bone contact, as well as the medial and inferior margin of eyebrows with a 45-degree injection angle in relation to midline with frontal bone contact. These three points are located inferior to the traditional (on-label) glabellar frown line injections used to treat the frontalis and the brow depressors.

The researchers used the 5-point glabellar line severity scale to evaluate the time of effect onset and the injection-related outcome 120 days after the treatment in 27 men and 78 women. They found that the onset of the neuromodulator effect occurred in an average of 3.5 days, and no adverse events such as eyebrow ptosis, upper eyelid ptosis, medial eyebrow ptosis, and lateral frontalis hyperactivity occurred during the study period.

“If you inject the origin of these muscles, you can get a brow lift with this technique by avoiding frontalis altogether,” Dr. Green said. “The caveat is, it’s so great at lifting the brows that if you treat the forehead, you may create a midline horizontal ‘shelf’ like I’ve never seen before, where the eyebrows elevate into an immobile superior frontalis.”

To avoid this when treating the forehead as well, he’s learned to split the dose of neuromodulator. “If I was injecting 5 units in the procerus before, I’ll do 2.5 units on nasal bone at the insertion of the muscle and then 2.5 units higher up in the traditional midline procerus injection site,” Dr. Green said.

“Same with the corrugators,” he continued. “Then, remember to inject more superficially in the lateral part, the tail of the corrugators, because the tail of the corrugators is inserting into the undersurface of the dermis. That’s why you see that skin puckering in the lateral brows when people frown. You’re pretty safe to chase that laterally if the brow’s already flat as in men, but I caution you [not] to do that in women, because you may flatten the brow.”

Dr. Green said that he is aware of two cases of lid ptosis from the 3-point technique, one of which happened to him.

“When you’re on the bone with your thumb you can feel that liquid traveling along the bone,” he said. “It can travel all the way to the midline pupil where the levator palpebrae superioris muscle is. I now don’t come in contact with bone with my corrugator origin injections, but rather float the needle a couple of millimeters off bone (in muscle) to hopefully prevent that from happening. Alternatively, some people will compress the brow along frontal bone lateral to that corrugator injection site while they’re injecting to prevent backflow of the neuromodulator.”

Dr. Green reported having received research funding and/or consulting fees from many device and pharmaceutical companies.

SAN DIEGO – In the clinical experience of Jeremy B. Green, MD, men typically require a higher dose of facial neuromodulators for nonsurgical wrinkle reduction compared with women because of anatomical differences.

“Men generally have larger facial muscle mass,” Dr. Green, a dermatologist in Coral Gables, Fla., said at the annual Masters of Aesthetics Symposium. “We need a higher dose to treat them, or they will not be happy. In general, I try to increase the dose by about 50% for my male patients.”

Two early trials of dose adjustments support this practice, he said. In one, 80 men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (Botox) in the glabellar area. The researchers found that the 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose.

In a subsequent study, researchers administered botulinum toxin type A (Dysport) 0.5 to 0.7 mL for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation at several time points up to 150 days post treatment. The median duration of effect was 109 days vs. 0 days for placebo in the blinded evaluator evaluation and 107 days vs. 0 for placebo in the patient self-evaluation.

Most injection algorithms for treating the glabella rely on a 5- or 7-point injection technique, but in 2021, researchers led by Sebastian Cotofana, MD, PhD, of the department of clinical anatomy at Mayo Clinic, Rochester, Minn., reported results from a study of the efficacy and safety of a refined 3-point injection technique targeting horizontal and vertical lines to prevent brow ptosis.

“Prior to this study Sebastian asked me, ‘Why do you guys always inject the body of the muscle?’ ” Dr. Green said. “‘If you inject the origin of the muscle on bone, you could more effectively wipe out the entire muscle’s movement. You’re going to get a better result at a lower dose, so let’s study this.’”

The injection technique involves targeting the midline level of the connecting line between left and right medial canthal ligaments with a 90-degree injection angle with bone contact, as well as the medial and inferior margin of eyebrows with a 45-degree injection angle in relation to midline with frontal bone contact. These three points are located inferior to the traditional (on-label) glabellar frown line injections used to treat the frontalis and the brow depressors.

The researchers used the 5-point glabellar line severity scale to evaluate the time of effect onset and the injection-related outcome 120 days after the treatment in 27 men and 78 women. They found that the onset of the neuromodulator effect occurred in an average of 3.5 days, and no adverse events such as eyebrow ptosis, upper eyelid ptosis, medial eyebrow ptosis, and lateral frontalis hyperactivity occurred during the study period.

“If you inject the origin of these muscles, you can get a brow lift with this technique by avoiding frontalis altogether,” Dr. Green said. “The caveat is, it’s so great at lifting the brows that if you treat the forehead, you may create a midline horizontal ‘shelf’ like I’ve never seen before, where the eyebrows elevate into an immobile superior frontalis.”

To avoid this when treating the forehead as well, he’s learned to split the dose of neuromodulator. “If I was injecting 5 units in the procerus before, I’ll do 2.5 units on nasal bone at the insertion of the muscle and then 2.5 units higher up in the traditional midline procerus injection site,” Dr. Green said.

“Same with the corrugators,” he continued. “Then, remember to inject more superficially in the lateral part, the tail of the corrugators, because the tail of the corrugators is inserting into the undersurface of the dermis. That’s why you see that skin puckering in the lateral brows when people frown. You’re pretty safe to chase that laterally if the brow’s already flat as in men, but I caution you [not] to do that in women, because you may flatten the brow.”

Dr. Green said that he is aware of two cases of lid ptosis from the 3-point technique, one of which happened to him.

“When you’re on the bone with your thumb you can feel that liquid traveling along the bone,” he said. “It can travel all the way to the midline pupil where the levator palpebrae superioris muscle is. I now don’t come in contact with bone with my corrugator origin injections, but rather float the needle a couple of millimeters off bone (in muscle) to hopefully prevent that from happening. Alternatively, some people will compress the brow along frontal bone lateral to that corrugator injection site while they’re injecting to prevent backflow of the neuromodulator.”

Dr. Green reported having received research funding and/or consulting fees from many device and pharmaceutical companies.