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Novel acne drug now under review at the FDA
LAHAINA, HAWAII – by the Food and Drug Administration, is already generating considerable buzz in the patient-advocacy community even though the agency won’t issue its decision until August.
“I’ve actually had a lot of interest in this already from parents, especially regarding girls who have very hormonal acne but the parents are really not interested in starting them on a systemic hormonal therapy at their age,” Jessica Sprague, MD, said at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Clascoterone targets androgen receptors in the skin in order to reduce cutaneous 5-alpha dihydrotestosterone.
“It’s being developed for use in both males and females, which is great because at this point there’s no hormonal treatment for males,” noted Dr. Sprague, a pediatric dermatologist at Rady Children’s Hospital and the University of California, both in San Diego.
The manufacturer’s application for marketing approval of clascoterone cream 1% under FDA review includes evidence from two identical phase-3, double-blind, vehicle-controlled, 12-week, randomized trials. The two studies included a total of 1,440 patients aged 9 years through adulthood with moderate to severe facial acne vulgaris who were randomized to twice-daily application of clascoterone or its vehicle.
The primary outcome was the reduction in inflammatory lesions at week 12: a 46.2% decline from baseline with clascoterone 1% cream, which was a significantly greater improvement than the 32.7% reduction for vehicle. The secondary outcome – change in noninflammatory lesion counts at week 12 – was also positive for the topical androgen receptor inhibitor, which achieved a 29.8% reduction, compared with 18.9% for vehicle. Clascoterone exhibited a favorable safety and tolerability profile, with numerically fewer treatment-emergent adverse events than in the vehicle control group. A stronger formulation of the topical agent is in advanced clinical trials for the treatment of androgenetic alopecia in both males and females.
Dr. Sprague reported having no financial conflicts regarding her presentation.
The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – by the Food and Drug Administration, is already generating considerable buzz in the patient-advocacy community even though the agency won’t issue its decision until August.
“I’ve actually had a lot of interest in this already from parents, especially regarding girls who have very hormonal acne but the parents are really not interested in starting them on a systemic hormonal therapy at their age,” Jessica Sprague, MD, said at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Clascoterone targets androgen receptors in the skin in order to reduce cutaneous 5-alpha dihydrotestosterone.
“It’s being developed for use in both males and females, which is great because at this point there’s no hormonal treatment for males,” noted Dr. Sprague, a pediatric dermatologist at Rady Children’s Hospital and the University of California, both in San Diego.
The manufacturer’s application for marketing approval of clascoterone cream 1% under FDA review includes evidence from two identical phase-3, double-blind, vehicle-controlled, 12-week, randomized trials. The two studies included a total of 1,440 patients aged 9 years through adulthood with moderate to severe facial acne vulgaris who were randomized to twice-daily application of clascoterone or its vehicle.
The primary outcome was the reduction in inflammatory lesions at week 12: a 46.2% decline from baseline with clascoterone 1% cream, which was a significantly greater improvement than the 32.7% reduction for vehicle. The secondary outcome – change in noninflammatory lesion counts at week 12 – was also positive for the topical androgen receptor inhibitor, which achieved a 29.8% reduction, compared with 18.9% for vehicle. Clascoterone exhibited a favorable safety and tolerability profile, with numerically fewer treatment-emergent adverse events than in the vehicle control group. A stronger formulation of the topical agent is in advanced clinical trials for the treatment of androgenetic alopecia in both males and females.
Dr. Sprague reported having no financial conflicts regarding her presentation.
The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – by the Food and Drug Administration, is already generating considerable buzz in the patient-advocacy community even though the agency won’t issue its decision until August.
“I’ve actually had a lot of interest in this already from parents, especially regarding girls who have very hormonal acne but the parents are really not interested in starting them on a systemic hormonal therapy at their age,” Jessica Sprague, MD, said at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Clascoterone targets androgen receptors in the skin in order to reduce cutaneous 5-alpha dihydrotestosterone.
“It’s being developed for use in both males and females, which is great because at this point there’s no hormonal treatment for males,” noted Dr. Sprague, a pediatric dermatologist at Rady Children’s Hospital and the University of California, both in San Diego.
The manufacturer’s application for marketing approval of clascoterone cream 1% under FDA review includes evidence from two identical phase-3, double-blind, vehicle-controlled, 12-week, randomized trials. The two studies included a total of 1,440 patients aged 9 years through adulthood with moderate to severe facial acne vulgaris who were randomized to twice-daily application of clascoterone or its vehicle.
The primary outcome was the reduction in inflammatory lesions at week 12: a 46.2% decline from baseline with clascoterone 1% cream, which was a significantly greater improvement than the 32.7% reduction for vehicle. The secondary outcome – change in noninflammatory lesion counts at week 12 – was also positive for the topical androgen receptor inhibitor, which achieved a 29.8% reduction, compared with 18.9% for vehicle. Clascoterone exhibited a favorable safety and tolerability profile, with numerically fewer treatment-emergent adverse events than in the vehicle control group. A stronger formulation of the topical agent is in advanced clinical trials for the treatment of androgenetic alopecia in both males and females.
Dr. Sprague reported having no financial conflicts regarding her presentation.
The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM THE SDEF HAWAII DERMATOLOGY SEMINAR
iPLEDGE allows at-home pregnancy tests during pandemic
tests to comply with the requirements of the iPLEDGE program during the COVID-19 pandemic, according to an update program posted on the iPLEDGE website.
The program’s other requirements – the prescription window and two forms of birth control – remain unchanged.
The change follows recent guidance from the Department of Health & Human Services and the Food and Drug Administration regarding accommodations for medical care and drugs subject to Risk Evaluation and Mitigation Strategies (REMS) in the midst of a public health emergency that requires most people to remain in their homes except for essential services.
Allowing females to take at-home pregnancy tests and communicate the results to physician according to their preference is “a game changer for the middle of a pandemic, obviously,” Neil Goldberg, MD, a dermatologist in Westchester County, New York, said in an interview. “These are patients who don’t need to spend time outside just to get pregnancy tests done. It makes it a lot easier.”
Dr. Goldberg is frustrated, however, that the accommodations have not been more widely publicized; he discovered the change incidentally when speaking to an iPLEDGE program representative to request a waiver for a patient who had taken her pregnancy test too early. The program had denied a similar request for a 15-year-old patient of his the previous week, despite the patient being abstinent and having been in shelter-in-place for several weeks.
“The size of your notice [on the website] should be proportionate to how important it is,” Dr. Goldberg said, and the small red box on the site is easy to miss. By contrast, asking anyone to leave their homes to go to a lab for a pregnancy test in the midst of a global pandemic so they can continue their medication would be putting patients at risk, he added.
The iPLEDGE program is designed in part to ensure unplanned pregnancies do not occur in females while taking the teratogenic acne drug. But the rules are onerous and difficult even during normal times, pointed out Hilary Baldwin, MD, medical director of the Acne Treatment and Research Center in New York City and past president of the American Acne and Rosacea Society.
Male patients taking isotretinoin must visit their physician every month to get a new no-refills prescription, but females must get a pregnancy test at a Clinical Laboratory Improvement Amendments–certified lab, which must then provide physical results to the prescribing physician. The doctor enters the negative pregnancy test and the two forms of birth control the patient is taking in the iPLEDGE program site.
Then the patient must take an online test at home to acknowledge they understand what it means to not get pregnant and enter the two forms of birth control they are using – which must match what the doctor enters – before the pharmacy can dispense the drug. The entire process must occur within 7 days or else the patient has to wait 19 days before starting the process over.
“We run a very tight schedule for girls. And every month, we would worry that something would interfere, a snow storm or something else, and that they wouldn’t be able to complete their objectives within the 7-day period,” Dr Baldwin said in an interview. “It was always difficult, and now with us not being able to see the patient and the patient not wanting to go to the lab, this became completely impossible.”
Until this change, some patients may not have been able to get their prescription for severe nodulocystic acne, which can cause physical and psychological scarring, and “postponing treatment increases the likelihood of scarring,” Dr. Baldwin pointed out.
Dr. Goldberg’s patients now take a pregnancy test at home and send him a photo of the negative test that he then inserts into their EMR.
According to a March 17 statement from HHS, potential penalties for HIPAA violations are waived for good-faith use of “everyday communication technologies,” such as Skype or FaceTime, for telehealth treatment or diagnostics. The change was intended to allow telehealth services to continue healthcare for practices that had not previously had secure telehealth technology established.
Despite the changes for at-home pregnancy tests for females and in-person visits for all patients, the program has not altered the 7-day prescription window or the requirement to have two forms of birth control.
With reports of a global condom shortage, Dr Baldwin said she has more concerns about her adult patients being able to find a required barrier method of birth control than about her adolescent patients.
“This is a unique opportunity for us to trust our teenage patients because they can’t leave the house,” Dr. Baldwin said. “I’m actually more worried about my adult women on the drug who are bored and cooped up in a house with their significant other.”
Dr. Baldwin and Dr. Goldberg had no relevant disclosures. Dr. Goldberg is a Dermatology News board member.
tests to comply with the requirements of the iPLEDGE program during the COVID-19 pandemic, according to an update program posted on the iPLEDGE website.
The program’s other requirements – the prescription window and two forms of birth control – remain unchanged.
The change follows recent guidance from the Department of Health & Human Services and the Food and Drug Administration regarding accommodations for medical care and drugs subject to Risk Evaluation and Mitigation Strategies (REMS) in the midst of a public health emergency that requires most people to remain in their homes except for essential services.
Allowing females to take at-home pregnancy tests and communicate the results to physician according to their preference is “a game changer for the middle of a pandemic, obviously,” Neil Goldberg, MD, a dermatologist in Westchester County, New York, said in an interview. “These are patients who don’t need to spend time outside just to get pregnancy tests done. It makes it a lot easier.”
Dr. Goldberg is frustrated, however, that the accommodations have not been more widely publicized; he discovered the change incidentally when speaking to an iPLEDGE program representative to request a waiver for a patient who had taken her pregnancy test too early. The program had denied a similar request for a 15-year-old patient of his the previous week, despite the patient being abstinent and having been in shelter-in-place for several weeks.
“The size of your notice [on the website] should be proportionate to how important it is,” Dr. Goldberg said, and the small red box on the site is easy to miss. By contrast, asking anyone to leave their homes to go to a lab for a pregnancy test in the midst of a global pandemic so they can continue their medication would be putting patients at risk, he added.
The iPLEDGE program is designed in part to ensure unplanned pregnancies do not occur in females while taking the teratogenic acne drug. But the rules are onerous and difficult even during normal times, pointed out Hilary Baldwin, MD, medical director of the Acne Treatment and Research Center in New York City and past president of the American Acne and Rosacea Society.
Male patients taking isotretinoin must visit their physician every month to get a new no-refills prescription, but females must get a pregnancy test at a Clinical Laboratory Improvement Amendments–certified lab, which must then provide physical results to the prescribing physician. The doctor enters the negative pregnancy test and the two forms of birth control the patient is taking in the iPLEDGE program site.
Then the patient must take an online test at home to acknowledge they understand what it means to not get pregnant and enter the two forms of birth control they are using – which must match what the doctor enters – before the pharmacy can dispense the drug. The entire process must occur within 7 days or else the patient has to wait 19 days before starting the process over.
“We run a very tight schedule for girls. And every month, we would worry that something would interfere, a snow storm or something else, and that they wouldn’t be able to complete their objectives within the 7-day period,” Dr Baldwin said in an interview. “It was always difficult, and now with us not being able to see the patient and the patient not wanting to go to the lab, this became completely impossible.”
Until this change, some patients may not have been able to get their prescription for severe nodulocystic acne, which can cause physical and psychological scarring, and “postponing treatment increases the likelihood of scarring,” Dr. Baldwin pointed out.
Dr. Goldberg’s patients now take a pregnancy test at home and send him a photo of the negative test that he then inserts into their EMR.
According to a March 17 statement from HHS, potential penalties for HIPAA violations are waived for good-faith use of “everyday communication technologies,” such as Skype or FaceTime, for telehealth treatment or diagnostics. The change was intended to allow telehealth services to continue healthcare for practices that had not previously had secure telehealth technology established.
Despite the changes for at-home pregnancy tests for females and in-person visits for all patients, the program has not altered the 7-day prescription window or the requirement to have two forms of birth control.
With reports of a global condom shortage, Dr Baldwin said she has more concerns about her adult patients being able to find a required barrier method of birth control than about her adolescent patients.
“This is a unique opportunity for us to trust our teenage patients because they can’t leave the house,” Dr. Baldwin said. “I’m actually more worried about my adult women on the drug who are bored and cooped up in a house with their significant other.”
Dr. Baldwin and Dr. Goldberg had no relevant disclosures. Dr. Goldberg is a Dermatology News board member.
tests to comply with the requirements of the iPLEDGE program during the COVID-19 pandemic, according to an update program posted on the iPLEDGE website.
The program’s other requirements – the prescription window and two forms of birth control – remain unchanged.
The change follows recent guidance from the Department of Health & Human Services and the Food and Drug Administration regarding accommodations for medical care and drugs subject to Risk Evaluation and Mitigation Strategies (REMS) in the midst of a public health emergency that requires most people to remain in their homes except for essential services.
Allowing females to take at-home pregnancy tests and communicate the results to physician according to their preference is “a game changer for the middle of a pandemic, obviously,” Neil Goldberg, MD, a dermatologist in Westchester County, New York, said in an interview. “These are patients who don’t need to spend time outside just to get pregnancy tests done. It makes it a lot easier.”
Dr. Goldberg is frustrated, however, that the accommodations have not been more widely publicized; he discovered the change incidentally when speaking to an iPLEDGE program representative to request a waiver for a patient who had taken her pregnancy test too early. The program had denied a similar request for a 15-year-old patient of his the previous week, despite the patient being abstinent and having been in shelter-in-place for several weeks.
“The size of your notice [on the website] should be proportionate to how important it is,” Dr. Goldberg said, and the small red box on the site is easy to miss. By contrast, asking anyone to leave their homes to go to a lab for a pregnancy test in the midst of a global pandemic so they can continue their medication would be putting patients at risk, he added.
The iPLEDGE program is designed in part to ensure unplanned pregnancies do not occur in females while taking the teratogenic acne drug. But the rules are onerous and difficult even during normal times, pointed out Hilary Baldwin, MD, medical director of the Acne Treatment and Research Center in New York City and past president of the American Acne and Rosacea Society.
Male patients taking isotretinoin must visit their physician every month to get a new no-refills prescription, but females must get a pregnancy test at a Clinical Laboratory Improvement Amendments–certified lab, which must then provide physical results to the prescribing physician. The doctor enters the negative pregnancy test and the two forms of birth control the patient is taking in the iPLEDGE program site.
Then the patient must take an online test at home to acknowledge they understand what it means to not get pregnant and enter the two forms of birth control they are using – which must match what the doctor enters – before the pharmacy can dispense the drug. The entire process must occur within 7 days or else the patient has to wait 19 days before starting the process over.
“We run a very tight schedule for girls. And every month, we would worry that something would interfere, a snow storm or something else, and that they wouldn’t be able to complete their objectives within the 7-day period,” Dr Baldwin said in an interview. “It was always difficult, and now with us not being able to see the patient and the patient not wanting to go to the lab, this became completely impossible.”
Until this change, some patients may not have been able to get their prescription for severe nodulocystic acne, which can cause physical and psychological scarring, and “postponing treatment increases the likelihood of scarring,” Dr. Baldwin pointed out.
Dr. Goldberg’s patients now take a pregnancy test at home and send him a photo of the negative test that he then inserts into their EMR.
According to a March 17 statement from HHS, potential penalties for HIPAA violations are waived for good-faith use of “everyday communication technologies,” such as Skype or FaceTime, for telehealth treatment or diagnostics. The change was intended to allow telehealth services to continue healthcare for practices that had not previously had secure telehealth technology established.
Despite the changes for at-home pregnancy tests for females and in-person visits for all patients, the program has not altered the 7-day prescription window or the requirement to have two forms of birth control.
With reports of a global condom shortage, Dr Baldwin said she has more concerns about her adult patients being able to find a required barrier method of birth control than about her adolescent patients.
“This is a unique opportunity for us to trust our teenage patients because they can’t leave the house,” Dr. Baldwin said. “I’m actually more worried about my adult women on the drug who are bored and cooped up in a house with their significant other.”
Dr. Baldwin and Dr. Goldberg had no relevant disclosures. Dr. Goldberg is a Dermatology News board member.
Routinely screen for depression in atopic dermatitis
Jonathan I. Silverberg, MD, PhD, declared in a video presentation during a virtual meeting held by the George Washington University department of dermatology.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
Dr. Silverberg presented highlights of his recent study of depression screening rates in the National Ambulatory Medical Care Survey, an annual population-based survey by the National Center for Health Statistics. He and his coinvestigator analyzed 9,345 office visits for atopic dermatitis (AD) and 2,085 for psoriasis (Br J Dermatol. 2019 Oct 24. doi: 10.1111/bjd.18629.). The picture that emerged showed that there is much room for improvement.
“We found that depression screening rates were abysmally low in atopic dermatitis patients, with less than 2% patients being screened. There was very little difference in screening rates between patients on an advanced therapy, like systemic phototherapy or a biologic, compared to those who were just on topical therapy alone, meaning even the more severe patients aren’t being asked these questions. And no difference between dermatologists and primary care physicians,” said Dr. Silverberg, director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington.
For Dr. Silverberg, known for his pioneering work documenting the marked yet often-underappreciated negative impact of AD on quality of life and mental health, these rock-bottom screening rates were particularly galling.
“There are very high rates of anxiety and depression amongst our patients with atopic dermatitis,” the dermatologist emphasized. “Mental health symptoms are an incredibly important domain in atopic dermatitis that we need to ask our patients about. We don’t ask enough.
“This to me is actually a very important symptom to measure. It’s not just a theoretical construct involved in understanding the burden of the disease, it’s something that’s actionable because most of these cases of mental health symptoms are reversible or modifiable with improved control of the atopic dermatitis,” he continued. “I use this as an indication to step up therapy. If a patient is clinically depressed and we believe that’s secondary to their chronic atopic dermatitis, this is a reason to step up therapy to something stronger.”
If the depressive symptoms don’t improve after stepping up the intensity of the dermatologic therapy, it’s probably time for the patient to see a mental health professional, Dr. Silverberg advised, adding, “I’m not telling every dermatology resident out there to become a psychiatrist.”
Depression and anxiety in AD: How common?
In an analysis of multiyear data from the Medical Expenditure Panel Surveys, an annual population-based project conducted by the Agency for Healthcare Research and Quality, Dr. Silverberg and a coinvestigator found that adults with AD were an adjusted 186% more likely than those without AD to screen positive for depressive symptoms on the two-item Patient Health Questionnaire (PHQ-2), with rates of 44.3% and 21.9%, respectively. The AD patients were also 500% more likely to screen positive for severe psychological distress, with a 25.9% rate of having a Kessler-6 index score of 13 or more, compared with 5.5% in adults without AD.
The rate of severe psychological distress was higher in adults with AD than in those with asthma, diabetes, hypertension, urticaria, or psoriasis, and was comparable with the rate in individuals with autoimmune disease (Ann Allergy Asthma Immunol. 2019 Aug;123[2]:179-85).
“It’s surprising when you think that the majority of the cases of atopic dermatitis in the population are mild and yet when you look at a population-based sample such as this you see a strong signal come up. It means that, with all the dilution of mild disease, the signal is still there. It emphasizes that even patients with mild disease get these depressive symptoms and psychosocial distress,” Dr. Silverberg observed.
In a separate analysis of the same national database, this time looking at Short Form-6D health utility scores – a measure of overall quality of life encompassing key domains including vitality, physical function, mental health, fatigue – adults with AD scored markedly worse than individuals with no chronic health disorders. Health utility scores were particularly low in adults with AD and comorbid symptoms of anxiety or depression, suggesting that those affective symptoms are major drivers of the demonstrably poor quality of life in adult AD (Ann Allergy Asthma Immunol. 2020 Jan;124[1]:88-9).
In the Atopic Dermatitis in America Study, Dr. Silverberg and coinvestigators cross-sectionally surveyed 2,893 adults using the seven-item Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) assessment instruments. Individuals with AD as determined using the modified U.K. Diagnostic Criteria had dramatically higher rates of both depression and anxiety. For example, the prevalence of a HADS-A score of 11 or more, which is considered to be case finding for clinically important anxiety, was 28.6% in adults with AD, nearly twice the 15.5% prevalence in those without the dermatologic disease. A HADS-D score of 11 or greater was present in 13.5% of subjects with AD and 9% of those without.
HADS-A and -D scores were higher in adults with moderate AD, compared with mild disease, and higher still in those with severe AD. Indeed, virtually all individuals with moderate to severe AD had symptoms of anxiety and depression, which in a large proportion had gone undiagnosed. A multivariate analysis strongly suggested that AD severity was the major driver of anxiety and depression in adults with AD (Br J Dermatol. 2019 Sep;181[3]:554-65).
An important finding was that 100% of adults with AD who had scores in the severe range on three validated measures of itch, frequency of symptoms, and lesion severity had borderline or abnormal scores on the HADS-A and -D.
“Of course, if you don’t ask, you’re not going to know about it,” Dr. Silverberg noted.
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.
Jonathan I. Silverberg, MD, PhD, declared in a video presentation during a virtual meeting held by the George Washington University department of dermatology.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
Dr. Silverberg presented highlights of his recent study of depression screening rates in the National Ambulatory Medical Care Survey, an annual population-based survey by the National Center for Health Statistics. He and his coinvestigator analyzed 9,345 office visits for atopic dermatitis (AD) and 2,085 for psoriasis (Br J Dermatol. 2019 Oct 24. doi: 10.1111/bjd.18629.). The picture that emerged showed that there is much room for improvement.
“We found that depression screening rates were abysmally low in atopic dermatitis patients, with less than 2% patients being screened. There was very little difference in screening rates between patients on an advanced therapy, like systemic phototherapy or a biologic, compared to those who were just on topical therapy alone, meaning even the more severe patients aren’t being asked these questions. And no difference between dermatologists and primary care physicians,” said Dr. Silverberg, director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington.
For Dr. Silverberg, known for his pioneering work documenting the marked yet often-underappreciated negative impact of AD on quality of life and mental health, these rock-bottom screening rates were particularly galling.
“There are very high rates of anxiety and depression amongst our patients with atopic dermatitis,” the dermatologist emphasized. “Mental health symptoms are an incredibly important domain in atopic dermatitis that we need to ask our patients about. We don’t ask enough.
“This to me is actually a very important symptom to measure. It’s not just a theoretical construct involved in understanding the burden of the disease, it’s something that’s actionable because most of these cases of mental health symptoms are reversible or modifiable with improved control of the atopic dermatitis,” he continued. “I use this as an indication to step up therapy. If a patient is clinically depressed and we believe that’s secondary to their chronic atopic dermatitis, this is a reason to step up therapy to something stronger.”
If the depressive symptoms don’t improve after stepping up the intensity of the dermatologic therapy, it’s probably time for the patient to see a mental health professional, Dr. Silverberg advised, adding, “I’m not telling every dermatology resident out there to become a psychiatrist.”
Depression and anxiety in AD: How common?
In an analysis of multiyear data from the Medical Expenditure Panel Surveys, an annual population-based project conducted by the Agency for Healthcare Research and Quality, Dr. Silverberg and a coinvestigator found that adults with AD were an adjusted 186% more likely than those without AD to screen positive for depressive symptoms on the two-item Patient Health Questionnaire (PHQ-2), with rates of 44.3% and 21.9%, respectively. The AD patients were also 500% more likely to screen positive for severe psychological distress, with a 25.9% rate of having a Kessler-6 index score of 13 or more, compared with 5.5% in adults without AD.
The rate of severe psychological distress was higher in adults with AD than in those with asthma, diabetes, hypertension, urticaria, or psoriasis, and was comparable with the rate in individuals with autoimmune disease (Ann Allergy Asthma Immunol. 2019 Aug;123[2]:179-85).
“It’s surprising when you think that the majority of the cases of atopic dermatitis in the population are mild and yet when you look at a population-based sample such as this you see a strong signal come up. It means that, with all the dilution of mild disease, the signal is still there. It emphasizes that even patients with mild disease get these depressive symptoms and psychosocial distress,” Dr. Silverberg observed.
In a separate analysis of the same national database, this time looking at Short Form-6D health utility scores – a measure of overall quality of life encompassing key domains including vitality, physical function, mental health, fatigue – adults with AD scored markedly worse than individuals with no chronic health disorders. Health utility scores were particularly low in adults with AD and comorbid symptoms of anxiety or depression, suggesting that those affective symptoms are major drivers of the demonstrably poor quality of life in adult AD (Ann Allergy Asthma Immunol. 2020 Jan;124[1]:88-9).
In the Atopic Dermatitis in America Study, Dr. Silverberg and coinvestigators cross-sectionally surveyed 2,893 adults using the seven-item Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) assessment instruments. Individuals with AD as determined using the modified U.K. Diagnostic Criteria had dramatically higher rates of both depression and anxiety. For example, the prevalence of a HADS-A score of 11 or more, which is considered to be case finding for clinically important anxiety, was 28.6% in adults with AD, nearly twice the 15.5% prevalence in those without the dermatologic disease. A HADS-D score of 11 or greater was present in 13.5% of subjects with AD and 9% of those without.
HADS-A and -D scores were higher in adults with moderate AD, compared with mild disease, and higher still in those with severe AD. Indeed, virtually all individuals with moderate to severe AD had symptoms of anxiety and depression, which in a large proportion had gone undiagnosed. A multivariate analysis strongly suggested that AD severity was the major driver of anxiety and depression in adults with AD (Br J Dermatol. 2019 Sep;181[3]:554-65).
An important finding was that 100% of adults with AD who had scores in the severe range on three validated measures of itch, frequency of symptoms, and lesion severity had borderline or abnormal scores on the HADS-A and -D.
“Of course, if you don’t ask, you’re not going to know about it,” Dr. Silverberg noted.
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.
Jonathan I. Silverberg, MD, PhD, declared in a video presentation during a virtual meeting held by the George Washington University department of dermatology.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
Dr. Silverberg presented highlights of his recent study of depression screening rates in the National Ambulatory Medical Care Survey, an annual population-based survey by the National Center for Health Statistics. He and his coinvestigator analyzed 9,345 office visits for atopic dermatitis (AD) and 2,085 for psoriasis (Br J Dermatol. 2019 Oct 24. doi: 10.1111/bjd.18629.). The picture that emerged showed that there is much room for improvement.
“We found that depression screening rates were abysmally low in atopic dermatitis patients, with less than 2% patients being screened. There was very little difference in screening rates between patients on an advanced therapy, like systemic phototherapy or a biologic, compared to those who were just on topical therapy alone, meaning even the more severe patients aren’t being asked these questions. And no difference between dermatologists and primary care physicians,” said Dr. Silverberg, director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington.
For Dr. Silverberg, known for his pioneering work documenting the marked yet often-underappreciated negative impact of AD on quality of life and mental health, these rock-bottom screening rates were particularly galling.
“There are very high rates of anxiety and depression amongst our patients with atopic dermatitis,” the dermatologist emphasized. “Mental health symptoms are an incredibly important domain in atopic dermatitis that we need to ask our patients about. We don’t ask enough.
“This to me is actually a very important symptom to measure. It’s not just a theoretical construct involved in understanding the burden of the disease, it’s something that’s actionable because most of these cases of mental health symptoms are reversible or modifiable with improved control of the atopic dermatitis,” he continued. “I use this as an indication to step up therapy. If a patient is clinically depressed and we believe that’s secondary to their chronic atopic dermatitis, this is a reason to step up therapy to something stronger.”
If the depressive symptoms don’t improve after stepping up the intensity of the dermatologic therapy, it’s probably time for the patient to see a mental health professional, Dr. Silverberg advised, adding, “I’m not telling every dermatology resident out there to become a psychiatrist.”
Depression and anxiety in AD: How common?
In an analysis of multiyear data from the Medical Expenditure Panel Surveys, an annual population-based project conducted by the Agency for Healthcare Research and Quality, Dr. Silverberg and a coinvestigator found that adults with AD were an adjusted 186% more likely than those without AD to screen positive for depressive symptoms on the two-item Patient Health Questionnaire (PHQ-2), with rates of 44.3% and 21.9%, respectively. The AD patients were also 500% more likely to screen positive for severe psychological distress, with a 25.9% rate of having a Kessler-6 index score of 13 or more, compared with 5.5% in adults without AD.
The rate of severe psychological distress was higher in adults with AD than in those with asthma, diabetes, hypertension, urticaria, or psoriasis, and was comparable with the rate in individuals with autoimmune disease (Ann Allergy Asthma Immunol. 2019 Aug;123[2]:179-85).
“It’s surprising when you think that the majority of the cases of atopic dermatitis in the population are mild and yet when you look at a population-based sample such as this you see a strong signal come up. It means that, with all the dilution of mild disease, the signal is still there. It emphasizes that even patients with mild disease get these depressive symptoms and psychosocial distress,” Dr. Silverberg observed.
In a separate analysis of the same national database, this time looking at Short Form-6D health utility scores – a measure of overall quality of life encompassing key domains including vitality, physical function, mental health, fatigue – adults with AD scored markedly worse than individuals with no chronic health disorders. Health utility scores were particularly low in adults with AD and comorbid symptoms of anxiety or depression, suggesting that those affective symptoms are major drivers of the demonstrably poor quality of life in adult AD (Ann Allergy Asthma Immunol. 2020 Jan;124[1]:88-9).
In the Atopic Dermatitis in America Study, Dr. Silverberg and coinvestigators cross-sectionally surveyed 2,893 adults using the seven-item Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) assessment instruments. Individuals with AD as determined using the modified U.K. Diagnostic Criteria had dramatically higher rates of both depression and anxiety. For example, the prevalence of a HADS-A score of 11 or more, which is considered to be case finding for clinically important anxiety, was 28.6% in adults with AD, nearly twice the 15.5% prevalence in those without the dermatologic disease. A HADS-D score of 11 or greater was present in 13.5% of subjects with AD and 9% of those without.
HADS-A and -D scores were higher in adults with moderate AD, compared with mild disease, and higher still in those with severe AD. Indeed, virtually all individuals with moderate to severe AD had symptoms of anxiety and depression, which in a large proportion had gone undiagnosed. A multivariate analysis strongly suggested that AD severity was the major driver of anxiety and depression in adults with AD (Br J Dermatol. 2019 Sep;181[3]:554-65).
An important finding was that 100% of adults with AD who had scores in the severe range on three validated measures of itch, frequency of symptoms, and lesion severity had borderline or abnormal scores on the HADS-A and -D.
“Of course, if you don’t ask, you’re not going to know about it,” Dr. Silverberg noted.
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.
Thickening of tattoo
A punch biopsy to rule out other causes of the patient’s signs and symptoms confirmed tattoo granulomas with sarcoidal nodules.
Tattoo granulomas can occur years after the initial placement of the tattoo. They appear, as in this case, as a thickening of the tattooed skin due to a hypersensitivity reaction to the foreign body. It has been more commonly reported in yellow and red inks but also has been reported in black ink. Sarcoidosis has been diagnosed based on occurrence in tattoos, but in this case, the patient’s calcium level was normal, chest X-ray showed no signs of adenopathy, and she had no symptoms of sarcoidosis such as fevers, chills, night sweats, or fatigue. Thus, no further work-up for systemic sarcoidosis was performed.
During the patient’s biopsy visit, she was started on oral montelukast 10 mg/d for a possible allergic reaction to the tattoo ink. By the time pathology results returned 1 week later, her itching and puffiness had resolved. Montelukast is a leukotriene antagonist that is approved by the US Food and Drug Administration (FDA) for use in asthma and allergic rhinitis; it is also used off label for chronic urticaria.
Usual therapies for tattoo granulomas include intralesional steroid injections or laser therapy to destroy the pigment. This patient had a large number of tattoos that would have required extensive laser therapy destruction of the pigment or numerous intralesional injections. Since she was no longer symptomatic, she elected to continue on the montelukast. She was cautioned about the possible development of suicidal ideation on this medication and was instructed to seek care if any such thoughts occurred.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
Tittelbach J, Peckruhn M, Schliemann S, et al. Sarcoidal foreign body reaction as a severe side-effect to permanent makeup: successful treatment with intralesional triamcinolone. Acta Derm Venereol. 2018;98:458-459.
A punch biopsy to rule out other causes of the patient’s signs and symptoms confirmed tattoo granulomas with sarcoidal nodules.
Tattoo granulomas can occur years after the initial placement of the tattoo. They appear, as in this case, as a thickening of the tattooed skin due to a hypersensitivity reaction to the foreign body. It has been more commonly reported in yellow and red inks but also has been reported in black ink. Sarcoidosis has been diagnosed based on occurrence in tattoos, but in this case, the patient’s calcium level was normal, chest X-ray showed no signs of adenopathy, and she had no symptoms of sarcoidosis such as fevers, chills, night sweats, or fatigue. Thus, no further work-up for systemic sarcoidosis was performed.
During the patient’s biopsy visit, she was started on oral montelukast 10 mg/d for a possible allergic reaction to the tattoo ink. By the time pathology results returned 1 week later, her itching and puffiness had resolved. Montelukast is a leukotriene antagonist that is approved by the US Food and Drug Administration (FDA) for use in asthma and allergic rhinitis; it is also used off label for chronic urticaria.
Usual therapies for tattoo granulomas include intralesional steroid injections or laser therapy to destroy the pigment. This patient had a large number of tattoos that would have required extensive laser therapy destruction of the pigment or numerous intralesional injections. Since she was no longer symptomatic, she elected to continue on the montelukast. She was cautioned about the possible development of suicidal ideation on this medication and was instructed to seek care if any such thoughts occurred.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
A punch biopsy to rule out other causes of the patient’s signs and symptoms confirmed tattoo granulomas with sarcoidal nodules.
Tattoo granulomas can occur years after the initial placement of the tattoo. They appear, as in this case, as a thickening of the tattooed skin due to a hypersensitivity reaction to the foreign body. It has been more commonly reported in yellow and red inks but also has been reported in black ink. Sarcoidosis has been diagnosed based on occurrence in tattoos, but in this case, the patient’s calcium level was normal, chest X-ray showed no signs of adenopathy, and she had no symptoms of sarcoidosis such as fevers, chills, night sweats, or fatigue. Thus, no further work-up for systemic sarcoidosis was performed.
During the patient’s biopsy visit, she was started on oral montelukast 10 mg/d for a possible allergic reaction to the tattoo ink. By the time pathology results returned 1 week later, her itching and puffiness had resolved. Montelukast is a leukotriene antagonist that is approved by the US Food and Drug Administration (FDA) for use in asthma and allergic rhinitis; it is also used off label for chronic urticaria.
Usual therapies for tattoo granulomas include intralesional steroid injections or laser therapy to destroy the pigment. This patient had a large number of tattoos that would have required extensive laser therapy destruction of the pigment or numerous intralesional injections. Since she was no longer symptomatic, she elected to continue on the montelukast. She was cautioned about the possible development of suicidal ideation on this medication and was instructed to seek care if any such thoughts occurred.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
Tittelbach J, Peckruhn M, Schliemann S, et al. Sarcoidal foreign body reaction as a severe side-effect to permanent makeup: successful treatment with intralesional triamcinolone. Acta Derm Venereol. 2018;98:458-459.
Tittelbach J, Peckruhn M, Schliemann S, et al. Sarcoidal foreign body reaction as a severe side-effect to permanent makeup: successful treatment with intralesional triamcinolone. Acta Derm Venereol. 2018;98:458-459.
Low-income DC communities have restricted access to iPLEDGE pharmacies
Residents of , results from a survey demonstrated.
Prescription of isotretinoin is regulated by the iPLEDGE program, which strives to ensure that no female patient starts isotretinoin therapy if pregnant and that no female patient on isotretinoin therapy becomes pregnant. “Over the years, many studies have criticized the program by demonstrating that iPLEDGE has promoted health care disparities,” Nidhi Shah said during a virtual meeting held by the George Washington University department of dermatology. “For example, racial minorities and women are more likely to be underprescribed isotretinoin, as well as face more delays in treatment.”
In an effort to evaluate the geographic distribution of iPLEDGE pharmacies in Washington DC, and its correlation with sociodemographic factors, Ms. Shah, a third-year medical student at the George Washington University, Washington, and colleagues obtained a list of active pharmacies in Washington from the local government. They also surveyed each outpatient pharmacy in the District of Columbia to verify their iPLEDGE registration status, for a total of 146 pharmacies.
Ms. Shah reported that 82% of all outpatient pharmacies were enrolled in iPLEDGE. However, enrollment significantly varied by the type of pharmacy. For example, 100% of chain pharmacies were enrolled, compared with 46% of independent pharmacies and 60% of hospital-based pharmacies.
When the researchers evaluated the number and type of iPLEDGE pharmacy by each of the eight wards in Washington, they observed a high density of pharmacies in wards 1 and 2, communities with a generally low proportion of residents who live in poverty, and low density of pharmacies in wards 7 and 8, communities with a higher proportion of residents who live in poverty. In addition, there were more independent than chain pharmacies in wards 7 and 8, and residents in those wards had a greater distance to travel to reach an iPLEDGE pharmacy, compared with residents who live in the other wards.
When Ms. Shah and colleagues examined the correlation between pharmacies per 10,000 residents and specific sociodemographic factors, they observed a strong, positive correlation between iPLEDGE pharmacy density and median household income (P = .0003). On the other hand, there was a strong negative correlation between iPLEDGE pharmacy density and the percentage of individuals with public insurance (P less than .0001), as well as the percentage of nonwhite individuals (P = .0009).
“Our study highlights the lack of isotretinoin-dispensing pharmacies in low-income communities,” Ms. Shah concluded. “Not only are there fewer such pharmacies available in low income communities, but the residents must also travel further to reach them. The spatial heterogeneity of iPLEDGE pharmacies may be an important patient barrier to timely access of isotretinoin, especially for female patients who have a strict 7-day window to collect their medication. We hope that future public health reform works to close this gap.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Ms. Shah reported having no disclosures.
Residents of , results from a survey demonstrated.
Prescription of isotretinoin is regulated by the iPLEDGE program, which strives to ensure that no female patient starts isotretinoin therapy if pregnant and that no female patient on isotretinoin therapy becomes pregnant. “Over the years, many studies have criticized the program by demonstrating that iPLEDGE has promoted health care disparities,” Nidhi Shah said during a virtual meeting held by the George Washington University department of dermatology. “For example, racial minorities and women are more likely to be underprescribed isotretinoin, as well as face more delays in treatment.”
In an effort to evaluate the geographic distribution of iPLEDGE pharmacies in Washington DC, and its correlation with sociodemographic factors, Ms. Shah, a third-year medical student at the George Washington University, Washington, and colleagues obtained a list of active pharmacies in Washington from the local government. They also surveyed each outpatient pharmacy in the District of Columbia to verify their iPLEDGE registration status, for a total of 146 pharmacies.
Ms. Shah reported that 82% of all outpatient pharmacies were enrolled in iPLEDGE. However, enrollment significantly varied by the type of pharmacy. For example, 100% of chain pharmacies were enrolled, compared with 46% of independent pharmacies and 60% of hospital-based pharmacies.
When the researchers evaluated the number and type of iPLEDGE pharmacy by each of the eight wards in Washington, they observed a high density of pharmacies in wards 1 and 2, communities with a generally low proportion of residents who live in poverty, and low density of pharmacies in wards 7 and 8, communities with a higher proportion of residents who live in poverty. In addition, there were more independent than chain pharmacies in wards 7 and 8, and residents in those wards had a greater distance to travel to reach an iPLEDGE pharmacy, compared with residents who live in the other wards.
When Ms. Shah and colleagues examined the correlation between pharmacies per 10,000 residents and specific sociodemographic factors, they observed a strong, positive correlation between iPLEDGE pharmacy density and median household income (P = .0003). On the other hand, there was a strong negative correlation between iPLEDGE pharmacy density and the percentage of individuals with public insurance (P less than .0001), as well as the percentage of nonwhite individuals (P = .0009).
“Our study highlights the lack of isotretinoin-dispensing pharmacies in low-income communities,” Ms. Shah concluded. “Not only are there fewer such pharmacies available in low income communities, but the residents must also travel further to reach them. The spatial heterogeneity of iPLEDGE pharmacies may be an important patient barrier to timely access of isotretinoin, especially for female patients who have a strict 7-day window to collect their medication. We hope that future public health reform works to close this gap.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Ms. Shah reported having no disclosures.
Residents of , results from a survey demonstrated.
Prescription of isotretinoin is regulated by the iPLEDGE program, which strives to ensure that no female patient starts isotretinoin therapy if pregnant and that no female patient on isotretinoin therapy becomes pregnant. “Over the years, many studies have criticized the program by demonstrating that iPLEDGE has promoted health care disparities,” Nidhi Shah said during a virtual meeting held by the George Washington University department of dermatology. “For example, racial minorities and women are more likely to be underprescribed isotretinoin, as well as face more delays in treatment.”
In an effort to evaluate the geographic distribution of iPLEDGE pharmacies in Washington DC, and its correlation with sociodemographic factors, Ms. Shah, a third-year medical student at the George Washington University, Washington, and colleagues obtained a list of active pharmacies in Washington from the local government. They also surveyed each outpatient pharmacy in the District of Columbia to verify their iPLEDGE registration status, for a total of 146 pharmacies.
Ms. Shah reported that 82% of all outpatient pharmacies were enrolled in iPLEDGE. However, enrollment significantly varied by the type of pharmacy. For example, 100% of chain pharmacies were enrolled, compared with 46% of independent pharmacies and 60% of hospital-based pharmacies.
When the researchers evaluated the number and type of iPLEDGE pharmacy by each of the eight wards in Washington, they observed a high density of pharmacies in wards 1 and 2, communities with a generally low proportion of residents who live in poverty, and low density of pharmacies in wards 7 and 8, communities with a higher proportion of residents who live in poverty. In addition, there were more independent than chain pharmacies in wards 7 and 8, and residents in those wards had a greater distance to travel to reach an iPLEDGE pharmacy, compared with residents who live in the other wards.
When Ms. Shah and colleagues examined the correlation between pharmacies per 10,000 residents and specific sociodemographic factors, they observed a strong, positive correlation between iPLEDGE pharmacy density and median household income (P = .0003). On the other hand, there was a strong negative correlation between iPLEDGE pharmacy density and the percentage of individuals with public insurance (P less than .0001), as well as the percentage of nonwhite individuals (P = .0009).
“Our study highlights the lack of isotretinoin-dispensing pharmacies in low-income communities,” Ms. Shah concluded. “Not only are there fewer such pharmacies available in low income communities, but the residents must also travel further to reach them. The spatial heterogeneity of iPLEDGE pharmacies may be an important patient barrier to timely access of isotretinoin, especially for female patients who have a strict 7-day window to collect their medication. We hope that future public health reform works to close this gap.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Ms. Shah reported having no disclosures.
Rapid shift to adalimumab biosimilars in Denmark contrasts with U.S. experience
Adalimumab biosimilars are years away from entering the marketplace in the United States because of patent disputes, but they already have led to substantial discounts in Denmark, researchers wrote in JAMA Internal Medicine.
The Danish health care system switched almost entirely to adalimumab biosimilars after the patent on the original adalimumab product, Humira, expired there in October 2018. The switch to biosimilars led to an 82% decrease in costs for the medication, wrote Thomas Bo Jensen, MD, and colleagues in a research letter.
Denmark did not automatically substitute biosimilars, but the Danish Medicines Council recommended adalimumab biosimilars for all indications following Humira’s patent expiration. The recommendations “included switching patients to a biosimilar who were already well treated with the originator,” the researchers wrote.
To study the shift to adalimumab biosimilars across all indications in Denmark and calculate cost reductions, Dr. Jensen, of the department of clinical pharmacology at Copenhagen University Hospital Bispebjerg, and coinvestigators examined monthly data on drug sales from Amgros, which purchases all hospital drugs in the country.
“The proportion of adalimumab biosimilars increased from 71.6% (7,040 of 9,829 pens) in November 2018 to 95.1% (8,974 of 9,438 pens) in December 2018,” the researchers wrote. “Costs of adalimumab decreased by 82.8% from September 2018 to December 2018 (September: 8,197 pens at $5.13 million; December: 9,438 pens at $1.01 million).” The results were similar in rheumatology, dermatology, and gastroenterology.
The Food and Drug Administration has approved five adalimumab biosimilars in the United States, but “they will not enter the market until 2023 owing to patent disputes with AbbVie, the manufacturer of Humira,” wrote Jennifer D. Claytor, MD, of the department of internal medicine at University of California, San Francisco, and Walid Gellad, MD, of the division of general internal medicine at University of Pittsburgh, in an accompanying editorial.
The annual postrebate price of Humira doubled between 2013 and 2018, from $19,000 to $38,000, and these price increases may influence the price of biosimilars, “which will be priced using Humira’s price as an anchor,” Dr. Claytor and Dr. Gellad wrote.
A rapid shift to adalimumab biosimilars across the United States when they become available is “unlikely,” they wrote. Nonetheless, “some health care systems of comparable size to Denmark (e.g., the Veterans Affairs system) and others that are larger (e.g., Kaiser Permanente) ... have the ability to switch products quickly through use of formularies and a prescriber workforce. For example, Kaiser Permanente has successfully replaced Remicade (infliximab) with biosimilars in 80% of patients.”
Given the many biologics in development and increasing health care spending, “we need to take seriously the substantial savings offered by biosimilars and the feasibility, as evidenced by Denmark, of switching to biosimilars quickly once they are available on the market,” Dr. Claytor and Dr. Gellad concluded.
The research was supported by an unrestricted grant from Helsefonden. One author disclosed receiving grants from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb outside the current study. The editorial authors had no disclosures.
SOURCE: Jensen TB et al. JAMA Intern Med. 2020 Mar 30. doi: 10.1001/jamainternmed.2020.0338.
Adalimumab biosimilars are years away from entering the marketplace in the United States because of patent disputes, but they already have led to substantial discounts in Denmark, researchers wrote in JAMA Internal Medicine.
The Danish health care system switched almost entirely to adalimumab biosimilars after the patent on the original adalimumab product, Humira, expired there in October 2018. The switch to biosimilars led to an 82% decrease in costs for the medication, wrote Thomas Bo Jensen, MD, and colleagues in a research letter.
Denmark did not automatically substitute biosimilars, but the Danish Medicines Council recommended adalimumab biosimilars for all indications following Humira’s patent expiration. The recommendations “included switching patients to a biosimilar who were already well treated with the originator,” the researchers wrote.
To study the shift to adalimumab biosimilars across all indications in Denmark and calculate cost reductions, Dr. Jensen, of the department of clinical pharmacology at Copenhagen University Hospital Bispebjerg, and coinvestigators examined monthly data on drug sales from Amgros, which purchases all hospital drugs in the country.
“The proportion of adalimumab biosimilars increased from 71.6% (7,040 of 9,829 pens) in November 2018 to 95.1% (8,974 of 9,438 pens) in December 2018,” the researchers wrote. “Costs of adalimumab decreased by 82.8% from September 2018 to December 2018 (September: 8,197 pens at $5.13 million; December: 9,438 pens at $1.01 million).” The results were similar in rheumatology, dermatology, and gastroenterology.
The Food and Drug Administration has approved five adalimumab biosimilars in the United States, but “they will not enter the market until 2023 owing to patent disputes with AbbVie, the manufacturer of Humira,” wrote Jennifer D. Claytor, MD, of the department of internal medicine at University of California, San Francisco, and Walid Gellad, MD, of the division of general internal medicine at University of Pittsburgh, in an accompanying editorial.
The annual postrebate price of Humira doubled between 2013 and 2018, from $19,000 to $38,000, and these price increases may influence the price of biosimilars, “which will be priced using Humira’s price as an anchor,” Dr. Claytor and Dr. Gellad wrote.
A rapid shift to adalimumab biosimilars across the United States when they become available is “unlikely,” they wrote. Nonetheless, “some health care systems of comparable size to Denmark (e.g., the Veterans Affairs system) and others that are larger (e.g., Kaiser Permanente) ... have the ability to switch products quickly through use of formularies and a prescriber workforce. For example, Kaiser Permanente has successfully replaced Remicade (infliximab) with biosimilars in 80% of patients.”
Given the many biologics in development and increasing health care spending, “we need to take seriously the substantial savings offered by biosimilars and the feasibility, as evidenced by Denmark, of switching to biosimilars quickly once they are available on the market,” Dr. Claytor and Dr. Gellad concluded.
The research was supported by an unrestricted grant from Helsefonden. One author disclosed receiving grants from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb outside the current study. The editorial authors had no disclosures.
SOURCE: Jensen TB et al. JAMA Intern Med. 2020 Mar 30. doi: 10.1001/jamainternmed.2020.0338.
Adalimumab biosimilars are years away from entering the marketplace in the United States because of patent disputes, but they already have led to substantial discounts in Denmark, researchers wrote in JAMA Internal Medicine.
The Danish health care system switched almost entirely to adalimumab biosimilars after the patent on the original adalimumab product, Humira, expired there in October 2018. The switch to biosimilars led to an 82% decrease in costs for the medication, wrote Thomas Bo Jensen, MD, and colleagues in a research letter.
Denmark did not automatically substitute biosimilars, but the Danish Medicines Council recommended adalimumab biosimilars for all indications following Humira’s patent expiration. The recommendations “included switching patients to a biosimilar who were already well treated with the originator,” the researchers wrote.
To study the shift to adalimumab biosimilars across all indications in Denmark and calculate cost reductions, Dr. Jensen, of the department of clinical pharmacology at Copenhagen University Hospital Bispebjerg, and coinvestigators examined monthly data on drug sales from Amgros, which purchases all hospital drugs in the country.
“The proportion of adalimumab biosimilars increased from 71.6% (7,040 of 9,829 pens) in November 2018 to 95.1% (8,974 of 9,438 pens) in December 2018,” the researchers wrote. “Costs of adalimumab decreased by 82.8% from September 2018 to December 2018 (September: 8,197 pens at $5.13 million; December: 9,438 pens at $1.01 million).” The results were similar in rheumatology, dermatology, and gastroenterology.
The Food and Drug Administration has approved five adalimumab biosimilars in the United States, but “they will not enter the market until 2023 owing to patent disputes with AbbVie, the manufacturer of Humira,” wrote Jennifer D. Claytor, MD, of the department of internal medicine at University of California, San Francisco, and Walid Gellad, MD, of the division of general internal medicine at University of Pittsburgh, in an accompanying editorial.
The annual postrebate price of Humira doubled between 2013 and 2018, from $19,000 to $38,000, and these price increases may influence the price of biosimilars, “which will be priced using Humira’s price as an anchor,” Dr. Claytor and Dr. Gellad wrote.
A rapid shift to adalimumab biosimilars across the United States when they become available is “unlikely,” they wrote. Nonetheless, “some health care systems of comparable size to Denmark (e.g., the Veterans Affairs system) and others that are larger (e.g., Kaiser Permanente) ... have the ability to switch products quickly through use of formularies and a prescriber workforce. For example, Kaiser Permanente has successfully replaced Remicade (infliximab) with biosimilars in 80% of patients.”
Given the many biologics in development and increasing health care spending, “we need to take seriously the substantial savings offered by biosimilars and the feasibility, as evidenced by Denmark, of switching to biosimilars quickly once they are available on the market,” Dr. Claytor and Dr. Gellad concluded.
The research was supported by an unrestricted grant from Helsefonden. One author disclosed receiving grants from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb outside the current study. The editorial authors had no disclosures.
SOURCE: Jensen TB et al. JAMA Intern Med. 2020 Mar 30. doi: 10.1001/jamainternmed.2020.0338.
FROM JAMA INTERNAL MEDICINE
FDA approves ixekizumab for pediatric plaque psoriasis
The according to an announcement from Lilly.
Patients need to be candidates for systemic therapy or phototherapy and have no known hypersensitivity to the biologic.
The safety, tolerability, and efficacy of the interleukin-17a antagonist were demonstrated in a phase 3 study that included 171 patients aged 6-17 years with moderate to severe plaque psoriasis. At 12 weeks, 89% those on ixekizumab achieved a 75% improvement on Psoriasis Area and Severity Index score, compared with 25% of those on placebo, and 81% achieved a static Physician’s Global Assessment of clear or almost clear, compared with 11% of those on placebo, according to the Lilly statement.
The safety profile seen with ixekizumab (Taltz) among the pediatric patients with plaque psoriasis is consistent with what has been observed among adult patients, although there were higher rates of conjunctivitis, influenza, and urticaria among the pediatric patients, the statement noted. The biologic may increase the risk of infection, and patients should be evaluated for tuberculosis, hypersensitivity, and inflammatory bowel disease. It is also recommended that routine immunizations be completed before initiating treatment.
Ixekizumab was initially approved for treating adults with moderate to severe plaque psoriasis in 2016, followed by approvals for treatment of adults with active psoriatic arthritis in 2017, and for adults with ankylosing spondylitis in August 2019.
The biologic therapies – etanercept, a tumor necrosis factor blocker, and ustekinumab (Stelara), an IL-12/23 antagonist – were previously approved by the FDA for pediatric psoriasis, in children ages 4 years and older and 12 years and older, respectively.
Updated prescribing information for ixekizumab can be found on the Lilly website.
[email protected]
The according to an announcement from Lilly.
Patients need to be candidates for systemic therapy or phototherapy and have no known hypersensitivity to the biologic.
The safety, tolerability, and efficacy of the interleukin-17a antagonist were demonstrated in a phase 3 study that included 171 patients aged 6-17 years with moderate to severe plaque psoriasis. At 12 weeks, 89% those on ixekizumab achieved a 75% improvement on Psoriasis Area and Severity Index score, compared with 25% of those on placebo, and 81% achieved a static Physician’s Global Assessment of clear or almost clear, compared with 11% of those on placebo, according to the Lilly statement.
The safety profile seen with ixekizumab (Taltz) among the pediatric patients with plaque psoriasis is consistent with what has been observed among adult patients, although there were higher rates of conjunctivitis, influenza, and urticaria among the pediatric patients, the statement noted. The biologic may increase the risk of infection, and patients should be evaluated for tuberculosis, hypersensitivity, and inflammatory bowel disease. It is also recommended that routine immunizations be completed before initiating treatment.
Ixekizumab was initially approved for treating adults with moderate to severe plaque psoriasis in 2016, followed by approvals for treatment of adults with active psoriatic arthritis in 2017, and for adults with ankylosing spondylitis in August 2019.
The biologic therapies – etanercept, a tumor necrosis factor blocker, and ustekinumab (Stelara), an IL-12/23 antagonist – were previously approved by the FDA for pediatric psoriasis, in children ages 4 years and older and 12 years and older, respectively.
Updated prescribing information for ixekizumab can be found on the Lilly website.
[email protected]
The according to an announcement from Lilly.
Patients need to be candidates for systemic therapy or phototherapy and have no known hypersensitivity to the biologic.
The safety, tolerability, and efficacy of the interleukin-17a antagonist were demonstrated in a phase 3 study that included 171 patients aged 6-17 years with moderate to severe plaque psoriasis. At 12 weeks, 89% those on ixekizumab achieved a 75% improvement on Psoriasis Area and Severity Index score, compared with 25% of those on placebo, and 81% achieved a static Physician’s Global Assessment of clear or almost clear, compared with 11% of those on placebo, according to the Lilly statement.
The safety profile seen with ixekizumab (Taltz) among the pediatric patients with plaque psoriasis is consistent with what has been observed among adult patients, although there were higher rates of conjunctivitis, influenza, and urticaria among the pediatric patients, the statement noted. The biologic may increase the risk of infection, and patients should be evaluated for tuberculosis, hypersensitivity, and inflammatory bowel disease. It is also recommended that routine immunizations be completed before initiating treatment.
Ixekizumab was initially approved for treating adults with moderate to severe plaque psoriasis in 2016, followed by approvals for treatment of adults with active psoriatic arthritis in 2017, and for adults with ankylosing spondylitis in August 2019.
The biologic therapies – etanercept, a tumor necrosis factor blocker, and ustekinumab (Stelara), an IL-12/23 antagonist – were previously approved by the FDA for pediatric psoriasis, in children ages 4 years and older and 12 years and older, respectively.
Updated prescribing information for ixekizumab can be found on the Lilly website.
[email protected]
Oral propranolol shown safe in PHACE
LAHAINA, HAWAII – Reassuring evidence of the safety of oral propranolol for treatment of complicated infantile hemangiomas in patients with PHACE syndrome comes from a recent multicenter study.
Oral propranolol is now well-ensconced as first-line therapy for complicated infantile hemangiomas in otherwise healthy children. However, the beta-blocker’s use in PHACE (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and Eye abnormalities) syndrome has been controversial, with concerns raised by some that it might raise the risk for arterial ischemic stroke. Not so, Moise L. Levy, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“I’m not suggesting you use propranolol with reckless abandon in this population, but this stroke concern is something that should be put to bed based on this study,” advised Dr. Levy, professor of dermatology and pediatrics at Dell Medical School in Austin, Tex., and physician-in-chief at Dell Children’s Medical Center.
PHACE syndrome is characterized by large, thick, plaque-like hemangiomas greater than 5 cm in size, most commonly on the face, although they can be located elsewhere.
“There was concern that if you found severely altered cerebrovascular arterial flow and you put a kid on a beta-blocker you might be causing some harm. But what I will tell you is that in this recently published paper this was not in fact an issue,” he said.
Dr. Levy was not an investigator in the multicenter retrospective study, which included 76 patients with PHACE syndrome treated for infantile hemangioma with oral propranolol at 0.3 mg/kg per dose or more at 11 academic tertiary care pediatric dermatology clinics. Treatment started at a median age of 56 days.
There were no strokes, TIAs, cardiovascular events, or other significant problems associated with treatment. Twenty-nine children experienced mild adverse events: minor gastrointestinal or respiratory symptoms, and sleep disturbances were threefold more frequent than reported with placebo in another study. The investigators noted that the safety experience in their PHACE syndrome population compared favorably with that in 726 infants without PHACE syndrome who received oral propranolol for hemangiomas, where the incidence of serious adverse events on treatment was 0.4% (JAMA Dermatol. 2019 Dec 11. doi: 10.1001/jamadermatol.2019.3839).
‘Hemangiomas – but we were taught that they go away’
Dr. Levy gave a shout-out to the American Academy of Pediatrics for publishing interdisciplinary expert consensus-based practice guidelines for the management of infantile hemangiomas, which he praised as “quite well done” (Pediatrics. 2019 Jan;143[1]. pii: e20183475. doi: 10.1542/peds.2018-3475).
Following release of the guidelines last year, he and other pediatric vascular anomalies experts saw an uptick in referrals from general pediatricians, which has since tapered off.
“It’s probably like for all of us: We read an article, it’s fresh on the mind, then you forget about the article and what you’ve read. So we need a little reinforcement from a learning perspective. This is a great article,” he said.
The guidelines debunk as myth the classic teaching that infantile hemangiomas go away. Explicit information is provided about the high-risk anatomic sites warranting consideration for early referral, including the periocular, lumbosacral, and perineal areas, the lip, and lower face.
“The major point is early identification of those lesions requiring evaluation and intervention. Hemangiomas generally speaking are at their ultimate size by 3-5 months of age. The bottom line is if you think something needs to be done, please send that patient, or act upon that patient, sooner rather than later. I can’t tell you how many cases of hemangiomas I’ve seen when the kid is 18 months of age, 3 years of age, 5 years, with a large area of redundant skin, scarring, or something of that sort, and it would have been really nice to have seen them earlier and acted upon them then,” the pediatric dermatologist said.
The guidelines recommend intervention or referral by 1 month of age, ideally. Guidance is provided about the use of oral propranolol as first-line therapy.
“Propranolol is something that has been a real game changer for us,” he noted. “Many people continue to be worried about side effects in using this, particularly in the young childhood population, but this paper shows pretty clearly that hypotension or bradycardia is not a real concern. I never hospitalize these patients for propranolol therapy except in high-risk populations: very preemie, any history of breathing problems. We check the blood pressure and heart rate at baseline, again at 7-10 days, and at every visit. We’ve never found any significant drop in blood pressure.”
Dr. Levy reported financial relationships with half a dozen pharmaceutical companies, none relevant to his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – Reassuring evidence of the safety of oral propranolol for treatment of complicated infantile hemangiomas in patients with PHACE syndrome comes from a recent multicenter study.
Oral propranolol is now well-ensconced as first-line therapy for complicated infantile hemangiomas in otherwise healthy children. However, the beta-blocker’s use in PHACE (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and Eye abnormalities) syndrome has been controversial, with concerns raised by some that it might raise the risk for arterial ischemic stroke. Not so, Moise L. Levy, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“I’m not suggesting you use propranolol with reckless abandon in this population, but this stroke concern is something that should be put to bed based on this study,” advised Dr. Levy, professor of dermatology and pediatrics at Dell Medical School in Austin, Tex., and physician-in-chief at Dell Children’s Medical Center.
PHACE syndrome is characterized by large, thick, plaque-like hemangiomas greater than 5 cm in size, most commonly on the face, although they can be located elsewhere.
“There was concern that if you found severely altered cerebrovascular arterial flow and you put a kid on a beta-blocker you might be causing some harm. But what I will tell you is that in this recently published paper this was not in fact an issue,” he said.
Dr. Levy was not an investigator in the multicenter retrospective study, which included 76 patients with PHACE syndrome treated for infantile hemangioma with oral propranolol at 0.3 mg/kg per dose or more at 11 academic tertiary care pediatric dermatology clinics. Treatment started at a median age of 56 days.
There were no strokes, TIAs, cardiovascular events, or other significant problems associated with treatment. Twenty-nine children experienced mild adverse events: minor gastrointestinal or respiratory symptoms, and sleep disturbances were threefold more frequent than reported with placebo in another study. The investigators noted that the safety experience in their PHACE syndrome population compared favorably with that in 726 infants without PHACE syndrome who received oral propranolol for hemangiomas, where the incidence of serious adverse events on treatment was 0.4% (JAMA Dermatol. 2019 Dec 11. doi: 10.1001/jamadermatol.2019.3839).
‘Hemangiomas – but we were taught that they go away’
Dr. Levy gave a shout-out to the American Academy of Pediatrics for publishing interdisciplinary expert consensus-based practice guidelines for the management of infantile hemangiomas, which he praised as “quite well done” (Pediatrics. 2019 Jan;143[1]. pii: e20183475. doi: 10.1542/peds.2018-3475).
Following release of the guidelines last year, he and other pediatric vascular anomalies experts saw an uptick in referrals from general pediatricians, which has since tapered off.
“It’s probably like for all of us: We read an article, it’s fresh on the mind, then you forget about the article and what you’ve read. So we need a little reinforcement from a learning perspective. This is a great article,” he said.
The guidelines debunk as myth the classic teaching that infantile hemangiomas go away. Explicit information is provided about the high-risk anatomic sites warranting consideration for early referral, including the periocular, lumbosacral, and perineal areas, the lip, and lower face.
“The major point is early identification of those lesions requiring evaluation and intervention. Hemangiomas generally speaking are at their ultimate size by 3-5 months of age. The bottom line is if you think something needs to be done, please send that patient, or act upon that patient, sooner rather than later. I can’t tell you how many cases of hemangiomas I’ve seen when the kid is 18 months of age, 3 years of age, 5 years, with a large area of redundant skin, scarring, or something of that sort, and it would have been really nice to have seen them earlier and acted upon them then,” the pediatric dermatologist said.
The guidelines recommend intervention or referral by 1 month of age, ideally. Guidance is provided about the use of oral propranolol as first-line therapy.
“Propranolol is something that has been a real game changer for us,” he noted. “Many people continue to be worried about side effects in using this, particularly in the young childhood population, but this paper shows pretty clearly that hypotension or bradycardia is not a real concern. I never hospitalize these patients for propranolol therapy except in high-risk populations: very preemie, any history of breathing problems. We check the blood pressure and heart rate at baseline, again at 7-10 days, and at every visit. We’ve never found any significant drop in blood pressure.”
Dr. Levy reported financial relationships with half a dozen pharmaceutical companies, none relevant to his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – Reassuring evidence of the safety of oral propranolol for treatment of complicated infantile hemangiomas in patients with PHACE syndrome comes from a recent multicenter study.
Oral propranolol is now well-ensconced as first-line therapy for complicated infantile hemangiomas in otherwise healthy children. However, the beta-blocker’s use in PHACE (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and Eye abnormalities) syndrome has been controversial, with concerns raised by some that it might raise the risk for arterial ischemic stroke. Not so, Moise L. Levy, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“I’m not suggesting you use propranolol with reckless abandon in this population, but this stroke concern is something that should be put to bed based on this study,” advised Dr. Levy, professor of dermatology and pediatrics at Dell Medical School in Austin, Tex., and physician-in-chief at Dell Children’s Medical Center.
PHACE syndrome is characterized by large, thick, plaque-like hemangiomas greater than 5 cm in size, most commonly on the face, although they can be located elsewhere.
“There was concern that if you found severely altered cerebrovascular arterial flow and you put a kid on a beta-blocker you might be causing some harm. But what I will tell you is that in this recently published paper this was not in fact an issue,” he said.
Dr. Levy was not an investigator in the multicenter retrospective study, which included 76 patients with PHACE syndrome treated for infantile hemangioma with oral propranolol at 0.3 mg/kg per dose or more at 11 academic tertiary care pediatric dermatology clinics. Treatment started at a median age of 56 days.
There were no strokes, TIAs, cardiovascular events, or other significant problems associated with treatment. Twenty-nine children experienced mild adverse events: minor gastrointestinal or respiratory symptoms, and sleep disturbances were threefold more frequent than reported with placebo in another study. The investigators noted that the safety experience in their PHACE syndrome population compared favorably with that in 726 infants without PHACE syndrome who received oral propranolol for hemangiomas, where the incidence of serious adverse events on treatment was 0.4% (JAMA Dermatol. 2019 Dec 11. doi: 10.1001/jamadermatol.2019.3839).
‘Hemangiomas – but we were taught that they go away’
Dr. Levy gave a shout-out to the American Academy of Pediatrics for publishing interdisciplinary expert consensus-based practice guidelines for the management of infantile hemangiomas, which he praised as “quite well done” (Pediatrics. 2019 Jan;143[1]. pii: e20183475. doi: 10.1542/peds.2018-3475).
Following release of the guidelines last year, he and other pediatric vascular anomalies experts saw an uptick in referrals from general pediatricians, which has since tapered off.
“It’s probably like for all of us: We read an article, it’s fresh on the mind, then you forget about the article and what you’ve read. So we need a little reinforcement from a learning perspective. This is a great article,” he said.
The guidelines debunk as myth the classic teaching that infantile hemangiomas go away. Explicit information is provided about the high-risk anatomic sites warranting consideration for early referral, including the periocular, lumbosacral, and perineal areas, the lip, and lower face.
“The major point is early identification of those lesions requiring evaluation and intervention. Hemangiomas generally speaking are at their ultimate size by 3-5 months of age. The bottom line is if you think something needs to be done, please send that patient, or act upon that patient, sooner rather than later. I can’t tell you how many cases of hemangiomas I’ve seen when the kid is 18 months of age, 3 years of age, 5 years, with a large area of redundant skin, scarring, or something of that sort, and it would have been really nice to have seen them earlier and acted upon them then,” the pediatric dermatologist said.
The guidelines recommend intervention or referral by 1 month of age, ideally. Guidance is provided about the use of oral propranolol as first-line therapy.
“Propranolol is something that has been a real game changer for us,” he noted. “Many people continue to be worried about side effects in using this, particularly in the young childhood population, but this paper shows pretty clearly that hypotension or bradycardia is not a real concern. I never hospitalize these patients for propranolol therapy except in high-risk populations: very preemie, any history of breathing problems. We check the blood pressure and heart rate at baseline, again at 7-10 days, and at every visit. We’ve never found any significant drop in blood pressure.”
Dr. Levy reported financial relationships with half a dozen pharmaceutical companies, none relevant to his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR
Don’t call it perioral dermatitis
LAHAINA, HAWAII – , according to Jessica Sprague, MD, a pediatric dermatologist at the University of California, San Diego, and Rady Children’s Hospital.
Years ago, some of her senior colleagues at the children’s hospital carried out a retrospective study of 79 patients, aged 6 months to 18 years, who were treated for what’s typically called perioral dermatitis. Of note, only 40% of patients had isolated perioral involvement, while 30% of the patients had no perioral lesions at all. Perinasal lesions were present in 43%, and 25% had periocular involvement, she noted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
The peak incidence of periorificial dermatitis in this series was under age 5 years. At presentation, the rash had been present for an average of 8 months. Seventy-two percent of patients had a history of exposure to corticosteroids, most often in the form of topical steroids, but in some cases inhaled or systemic steroids.
“Obviously you want to discontinue the topical steroid. Sometimes you need to taper them off, or you can switch to a topical calcineurin inhibitor [TCI] because they tend to flare a lot when you stop their topical steroid, although there are cases of TCIs precipitating periorificial dermatitis, so keep that in mind,” Dr. Sprague said.
If a patient is on inhaled steroids by mask for asthma, switching to a tube can sometimes limit the exposure, she continued.
Her first-line therapy for mild to moderate periorificial dermatitis, and the one supported by the strongest evidence base, is metronidazole cream. Other topical agents shown to be effective include azelaic acid, sulfacetamide, clindamycin, and topical calcineurin inhibitors.
Oral therapy is a good option for more extensive or recalcitrant cases.
“If parents are very anxious, like before school photos or holiday photos, sometimes I’ll use oral therapy as well. In younger kids, I prefer erythromycin at 30 mg/kg per day t.i.d. for 3-6 weeks. In kids 8 years old and up you can use doxycycline at 50-100 mg b.i.d., again for 3-6 weeks. And you have to tell them it’s going to take a while for this to go away,” Dr. Sprague said.
She reported having no financial conflicts regarding her presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – , according to Jessica Sprague, MD, a pediatric dermatologist at the University of California, San Diego, and Rady Children’s Hospital.
Years ago, some of her senior colleagues at the children’s hospital carried out a retrospective study of 79 patients, aged 6 months to 18 years, who were treated for what’s typically called perioral dermatitis. Of note, only 40% of patients had isolated perioral involvement, while 30% of the patients had no perioral lesions at all. Perinasal lesions were present in 43%, and 25% had periocular involvement, she noted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
The peak incidence of periorificial dermatitis in this series was under age 5 years. At presentation, the rash had been present for an average of 8 months. Seventy-two percent of patients had a history of exposure to corticosteroids, most often in the form of topical steroids, but in some cases inhaled or systemic steroids.
“Obviously you want to discontinue the topical steroid. Sometimes you need to taper them off, or you can switch to a topical calcineurin inhibitor [TCI] because they tend to flare a lot when you stop their topical steroid, although there are cases of TCIs precipitating periorificial dermatitis, so keep that in mind,” Dr. Sprague said.
If a patient is on inhaled steroids by mask for asthma, switching to a tube can sometimes limit the exposure, she continued.
Her first-line therapy for mild to moderate periorificial dermatitis, and the one supported by the strongest evidence base, is metronidazole cream. Other topical agents shown to be effective include azelaic acid, sulfacetamide, clindamycin, and topical calcineurin inhibitors.
Oral therapy is a good option for more extensive or recalcitrant cases.
“If parents are very anxious, like before school photos or holiday photos, sometimes I’ll use oral therapy as well. In younger kids, I prefer erythromycin at 30 mg/kg per day t.i.d. for 3-6 weeks. In kids 8 years old and up you can use doxycycline at 50-100 mg b.i.d., again for 3-6 weeks. And you have to tell them it’s going to take a while for this to go away,” Dr. Sprague said.
She reported having no financial conflicts regarding her presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – , according to Jessica Sprague, MD, a pediatric dermatologist at the University of California, San Diego, and Rady Children’s Hospital.
Years ago, some of her senior colleagues at the children’s hospital carried out a retrospective study of 79 patients, aged 6 months to 18 years, who were treated for what’s typically called perioral dermatitis. Of note, only 40% of patients had isolated perioral involvement, while 30% of the patients had no perioral lesions at all. Perinasal lesions were present in 43%, and 25% had periocular involvement, she noted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
The peak incidence of periorificial dermatitis in this series was under age 5 years. At presentation, the rash had been present for an average of 8 months. Seventy-two percent of patients had a history of exposure to corticosteroids, most often in the form of topical steroids, but in some cases inhaled or systemic steroids.
“Obviously you want to discontinue the topical steroid. Sometimes you need to taper them off, or you can switch to a topical calcineurin inhibitor [TCI] because they tend to flare a lot when you stop their topical steroid, although there are cases of TCIs precipitating periorificial dermatitis, so keep that in mind,” Dr. Sprague said.
If a patient is on inhaled steroids by mask for asthma, switching to a tube can sometimes limit the exposure, she continued.
Her first-line therapy for mild to moderate periorificial dermatitis, and the one supported by the strongest evidence base, is metronidazole cream. Other topical agents shown to be effective include azelaic acid, sulfacetamide, clindamycin, and topical calcineurin inhibitors.
Oral therapy is a good option for more extensive or recalcitrant cases.
“If parents are very anxious, like before school photos or holiday photos, sometimes I’ll use oral therapy as well. In younger kids, I prefer erythromycin at 30 mg/kg per day t.i.d. for 3-6 weeks. In kids 8 years old and up you can use doxycycline at 50-100 mg b.i.d., again for 3-6 weeks. And you have to tell them it’s going to take a while for this to go away,” Dr. Sprague said.
She reported having no financial conflicts regarding her presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR
New topicals coming for pediatric atopic dermatitis
LAHAINA, HAWAII – Novel topical medications are in the works that will address the longstanding unmet need for a Food and Drug Administration–approved noncorticosteroid topical for use in pediatric atopic dermatitis, Lawrence F. Eichenfield, MD, reported at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
These new agents will be embraced by clinicians for use in delicate skin areas, as well as in the common clinical scenario involving steroid-averse parents, predicted Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital.
First up is crisaborole (Eucrisa), which is approved for atopic dermatitis (AD) in children aged two years and older and has been under review at the Food and Drug Administration for use in infantile AD. (On March 24, several weeks after the meeting, the FDA approved crisaborole down to aged three months for treatment of mild to moderate AD). Agents earlier in the developmental pipeline include two topical Janus kinase (JAK) inhibitors, ruxolitinib and delgocitinib, as well as tapinarof.
Crisaborole: This phosphodiesterase 4 inhibitor is FDA approved down to 2 years of age. In the phase 4, open-label CrisADe CARE 1 study, crisaborole was studied in 137 children ages 3 months to under 24 months. CrisADe CARE 1, presented at the 2019 annual conference of the Pediatric Dermatology Research Alliance (PeDRA), showed close to a 60% reduction from baseline in Eczema Area and Severity Index (EASI) scores after 28 days of twice-daily therapy in the youngsters, 61% of who had moderate AD, the rest mild disease.
Tolerability and safety were reassuring in the phase 4 study. Although about 3% of subjects each experienced application site pain, discomfort, or erythema, the rate of study discontinuation was impressively low at 2.9%, Dr. Eichenfield observed.
Delgocitinib: Japanese investigators have reported positive results in a phase 2 study of delgocitinib ointment in 98 children and adolescents aged 2-15 years, with AD. After 4 weeks of twice-daily treatment, modified EASI scores improved by a mean of 54% with delgocitinib 0.25% and by 62% with 0.5%, compared with less than a 5% improvement with the vehicle control (J Allergy Clin Immunol. 2019 Dec;144[6]:1575-83). The ointment formulation is being developed specifically for the Japanese market.
Studies of an alternative formulation of the JAK inhibitor as a cream rather than ointment, intended for the U.S. and European markets, are in the early stages, conducted by Leo Pharma. Delgocitinib cream, under study in adults and children down to age 2 years with AD, is also under study for chronic hand dermatitis, a program Dr. Eichenfield is enthusiastic about.
“Hand eczema is something you’re going to hear a lot about in the next 2 years. In the U.S., we have no drug approved specifically for hand eczema. And we actually see a lot of hand eczema in pediatric and adolescent patients. I’d say 75%-80% of the ones I see also have atopic dermatitis,” he said.
Ruxolitinib: Incyte, which is developing the topical JAK inhibitor, recently announced positive results in the first of four phase 3 randomized trials, this one conducted in AD patients aged 12 years and older. The efficacy appears to be comparable to that of topical steroids. Studies in younger children are also planned. Ruxolitinib cream is in advanced clinical trials for treatment of vitiligo.
Tapinarof: This topical aryl hydrocarbon receptor agonist downregulates Th17 cytokines, an attribute desirable for treatment of psoriasis. But it also downregulates Th2 cytokines and improves the damaged skin barrier characteristic of AD via upregulation of the filaggrin and involucrin genes in keratinocytes. In a phase 2b, double-blind clinical trial conducted in 247 adults and adolescents with moderate to severe AD, 12 weeks of once-daily tapinarof 1% enabled 51% of patients to achieve a 75% or greater improvement in EASI scores, compared with 18% in controls on vehicle (J Am Acad Dermatol. 2019 Jan;80[1]:89-98.e3).
Dermavant, which is developing the drug, plans to seek an initial indication for treatment of psoriasis, where a phase 3 study is underway, before pursuing regulatory approval in AD.
Dr. Eichenfield disclosed serving as a consultant or investigator for various pharmaceutical companies, including Pfizer, and Dermavant.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
This article was updated 3/27/20.
LAHAINA, HAWAII – Novel topical medications are in the works that will address the longstanding unmet need for a Food and Drug Administration–approved noncorticosteroid topical for use in pediatric atopic dermatitis, Lawrence F. Eichenfield, MD, reported at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
These new agents will be embraced by clinicians for use in delicate skin areas, as well as in the common clinical scenario involving steroid-averse parents, predicted Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital.
First up is crisaborole (Eucrisa), which is approved for atopic dermatitis (AD) in children aged two years and older and has been under review at the Food and Drug Administration for use in infantile AD. (On March 24, several weeks after the meeting, the FDA approved crisaborole down to aged three months for treatment of mild to moderate AD). Agents earlier in the developmental pipeline include two topical Janus kinase (JAK) inhibitors, ruxolitinib and delgocitinib, as well as tapinarof.
Crisaborole: This phosphodiesterase 4 inhibitor is FDA approved down to 2 years of age. In the phase 4, open-label CrisADe CARE 1 study, crisaborole was studied in 137 children ages 3 months to under 24 months. CrisADe CARE 1, presented at the 2019 annual conference of the Pediatric Dermatology Research Alliance (PeDRA), showed close to a 60% reduction from baseline in Eczema Area and Severity Index (EASI) scores after 28 days of twice-daily therapy in the youngsters, 61% of who had moderate AD, the rest mild disease.
Tolerability and safety were reassuring in the phase 4 study. Although about 3% of subjects each experienced application site pain, discomfort, or erythema, the rate of study discontinuation was impressively low at 2.9%, Dr. Eichenfield observed.
Delgocitinib: Japanese investigators have reported positive results in a phase 2 study of delgocitinib ointment in 98 children and adolescents aged 2-15 years, with AD. After 4 weeks of twice-daily treatment, modified EASI scores improved by a mean of 54% with delgocitinib 0.25% and by 62% with 0.5%, compared with less than a 5% improvement with the vehicle control (J Allergy Clin Immunol. 2019 Dec;144[6]:1575-83). The ointment formulation is being developed specifically for the Japanese market.
Studies of an alternative formulation of the JAK inhibitor as a cream rather than ointment, intended for the U.S. and European markets, are in the early stages, conducted by Leo Pharma. Delgocitinib cream, under study in adults and children down to age 2 years with AD, is also under study for chronic hand dermatitis, a program Dr. Eichenfield is enthusiastic about.
“Hand eczema is something you’re going to hear a lot about in the next 2 years. In the U.S., we have no drug approved specifically for hand eczema. And we actually see a lot of hand eczema in pediatric and adolescent patients. I’d say 75%-80% of the ones I see also have atopic dermatitis,” he said.
Ruxolitinib: Incyte, which is developing the topical JAK inhibitor, recently announced positive results in the first of four phase 3 randomized trials, this one conducted in AD patients aged 12 years and older. The efficacy appears to be comparable to that of topical steroids. Studies in younger children are also planned. Ruxolitinib cream is in advanced clinical trials for treatment of vitiligo.
Tapinarof: This topical aryl hydrocarbon receptor agonist downregulates Th17 cytokines, an attribute desirable for treatment of psoriasis. But it also downregulates Th2 cytokines and improves the damaged skin barrier characteristic of AD via upregulation of the filaggrin and involucrin genes in keratinocytes. In a phase 2b, double-blind clinical trial conducted in 247 adults and adolescents with moderate to severe AD, 12 weeks of once-daily tapinarof 1% enabled 51% of patients to achieve a 75% or greater improvement in EASI scores, compared with 18% in controls on vehicle (J Am Acad Dermatol. 2019 Jan;80[1]:89-98.e3).
Dermavant, which is developing the drug, plans to seek an initial indication for treatment of psoriasis, where a phase 3 study is underway, before pursuing regulatory approval in AD.
Dr. Eichenfield disclosed serving as a consultant or investigator for various pharmaceutical companies, including Pfizer, and Dermavant.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
This article was updated 3/27/20.
LAHAINA, HAWAII – Novel topical medications are in the works that will address the longstanding unmet need for a Food and Drug Administration–approved noncorticosteroid topical for use in pediatric atopic dermatitis, Lawrence F. Eichenfield, MD, reported at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
These new agents will be embraced by clinicians for use in delicate skin areas, as well as in the common clinical scenario involving steroid-averse parents, predicted Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital.
First up is crisaborole (Eucrisa), which is approved for atopic dermatitis (AD) in children aged two years and older and has been under review at the Food and Drug Administration for use in infantile AD. (On March 24, several weeks after the meeting, the FDA approved crisaborole down to aged three months for treatment of mild to moderate AD). Agents earlier in the developmental pipeline include two topical Janus kinase (JAK) inhibitors, ruxolitinib and delgocitinib, as well as tapinarof.
Crisaborole: This phosphodiesterase 4 inhibitor is FDA approved down to 2 years of age. In the phase 4, open-label CrisADe CARE 1 study, crisaborole was studied in 137 children ages 3 months to under 24 months. CrisADe CARE 1, presented at the 2019 annual conference of the Pediatric Dermatology Research Alliance (PeDRA), showed close to a 60% reduction from baseline in Eczema Area and Severity Index (EASI) scores after 28 days of twice-daily therapy in the youngsters, 61% of who had moderate AD, the rest mild disease.
Tolerability and safety were reassuring in the phase 4 study. Although about 3% of subjects each experienced application site pain, discomfort, or erythema, the rate of study discontinuation was impressively low at 2.9%, Dr. Eichenfield observed.
Delgocitinib: Japanese investigators have reported positive results in a phase 2 study of delgocitinib ointment in 98 children and adolescents aged 2-15 years, with AD. After 4 weeks of twice-daily treatment, modified EASI scores improved by a mean of 54% with delgocitinib 0.25% and by 62% with 0.5%, compared with less than a 5% improvement with the vehicle control (J Allergy Clin Immunol. 2019 Dec;144[6]:1575-83). The ointment formulation is being developed specifically for the Japanese market.
Studies of an alternative formulation of the JAK inhibitor as a cream rather than ointment, intended for the U.S. and European markets, are in the early stages, conducted by Leo Pharma. Delgocitinib cream, under study in adults and children down to age 2 years with AD, is also under study for chronic hand dermatitis, a program Dr. Eichenfield is enthusiastic about.
“Hand eczema is something you’re going to hear a lot about in the next 2 years. In the U.S., we have no drug approved specifically for hand eczema. And we actually see a lot of hand eczema in pediatric and adolescent patients. I’d say 75%-80% of the ones I see also have atopic dermatitis,” he said.
Ruxolitinib: Incyte, which is developing the topical JAK inhibitor, recently announced positive results in the first of four phase 3 randomized trials, this one conducted in AD patients aged 12 years and older. The efficacy appears to be comparable to that of topical steroids. Studies in younger children are also planned. Ruxolitinib cream is in advanced clinical trials for treatment of vitiligo.
Tapinarof: This topical aryl hydrocarbon receptor agonist downregulates Th17 cytokines, an attribute desirable for treatment of psoriasis. But it also downregulates Th2 cytokines and improves the damaged skin barrier characteristic of AD via upregulation of the filaggrin and involucrin genes in keratinocytes. In a phase 2b, double-blind clinical trial conducted in 247 adults and adolescents with moderate to severe AD, 12 weeks of once-daily tapinarof 1% enabled 51% of patients to achieve a 75% or greater improvement in EASI scores, compared with 18% in controls on vehicle (J Am Acad Dermatol. 2019 Jan;80[1]:89-98.e3).
Dermavant, which is developing the drug, plans to seek an initial indication for treatment of psoriasis, where a phase 3 study is underway, before pursuing regulatory approval in AD.
Dr. Eichenfield disclosed serving as a consultant or investigator for various pharmaceutical companies, including Pfizer, and Dermavant.
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This article was updated 3/27/20.
REPORTING FROM THE SDEF HAWAII DERMATOLOGY SEMINAR