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Could ChatGPT write this column?
, but I am starting to think it is the real deal. Just how powerful is it? Well, ChatGPT might in fact be writing this column right now. It isn’t. No really, it’s me. But if not for the few cues (“super-buzzy”) that you’ll recognize as my writing voice, there might not be any way for you to know if I wrote this or not.
It’s perfectly OK if you’ve no clue what I’m talking about. ChatGPT is an AI chatbot that burst into public view just a couple months ago. Not your parent’s chatbot, this one is capable of answering questions in conversational language. It is jaw-droppingly good. Like Google, you can type in a question and it offers you answers. Rather than giving you a list of websites and a few Wikipedia blurbs, however, ChatGPT answers your question in human-like text. It can also create content on demand. For example, I asked it to write a Valentine poem to a dermatologist, and it gave me five stanzas starting with:
Oh gentle healer of skin so fair,
Not good enough to send to my wife. But not bad.
If you ask it again, it will create a whole new one for you. Amusing, yes? What if you asked ChatGPT to explain psoriasis, or any medical condition for that matter, to a patient? The replies are quite good. Some even better than what I’m currently using for my patients. It can also offer treatment recommendations, vacation advice, and plan, with recipes, a dinner party for six with one vegan and one gluten-free couple. If you are a programmer, it can write code. Ask it for a Wordpress plugin to add to your website and your eyes will widen as you see it magically appear before you. What if you find that you just don’t like your daughter’s new boyfriend? Yep, it will write the text or email for you to help with this discussion. I’ve saved that one.
I tried “What are treatments for bullous pemphigoid that has been refractory to topical steroid, oral prednisone, and oral tetracyclines?” It replied with five ideas, including the standard methotrexate and azathioprine but also IVIG, Rituxan, even other biologics. Write an op note? Appeal a denied prior authorization to a payer? Write a clinic note for a complete skin exam? Check, check, check. Are you starting to think it might be the real deal, too?
Before we sell the farm though, there are significant limitations. Despite how swotty ChatGPT seems, it is not smart. That is, “it” has no idea what “it” is saying. ChatGPT is an incredibly sophisticated algorithm that has learned the probability of what word comes next in a conversation. To do so, it read the Internet. Billions (trillions?) of words make it possible to predict what is the best answer to any question. But – it’s only as good as the Internet, so there’s that. My patient who used ChatGPT has dissecting cellulitis and asked what to do for scarring alopecia. Some of the answers were reasonable, but some, such as transplanting hairs into the scarred areas, would not likely be helpful. That is unless ChatGPT knows something I don’t.
Having wasted hours of time playing with this thing rather than writing my column, I asked ChatGPT to write an article about itself in the style of Christopher Hitchens. It was nothing like his incisive and eloquent prose, but it wrote 500 words in a few seconds ending with:
“The reality is that there is no substitute for human interaction and empathy in the field of dermatology. Dermatologists must be cautious in their adoption of ChatGPT and ensure that they are not sacrificing the quality of patient care in the pursuit of efficiency and convenience.”
I’m not sure I could have said it better myself.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
, but I am starting to think it is the real deal. Just how powerful is it? Well, ChatGPT might in fact be writing this column right now. It isn’t. No really, it’s me. But if not for the few cues (“super-buzzy”) that you’ll recognize as my writing voice, there might not be any way for you to know if I wrote this or not.
It’s perfectly OK if you’ve no clue what I’m talking about. ChatGPT is an AI chatbot that burst into public view just a couple months ago. Not your parent’s chatbot, this one is capable of answering questions in conversational language. It is jaw-droppingly good. Like Google, you can type in a question and it offers you answers. Rather than giving you a list of websites and a few Wikipedia blurbs, however, ChatGPT answers your question in human-like text. It can also create content on demand. For example, I asked it to write a Valentine poem to a dermatologist, and it gave me five stanzas starting with:
Oh gentle healer of skin so fair,
Not good enough to send to my wife. But not bad.
If you ask it again, it will create a whole new one for you. Amusing, yes? What if you asked ChatGPT to explain psoriasis, or any medical condition for that matter, to a patient? The replies are quite good. Some even better than what I’m currently using for my patients. It can also offer treatment recommendations, vacation advice, and plan, with recipes, a dinner party for six with one vegan and one gluten-free couple. If you are a programmer, it can write code. Ask it for a Wordpress plugin to add to your website and your eyes will widen as you see it magically appear before you. What if you find that you just don’t like your daughter’s new boyfriend? Yep, it will write the text or email for you to help with this discussion. I’ve saved that one.
I tried “What are treatments for bullous pemphigoid that has been refractory to topical steroid, oral prednisone, and oral tetracyclines?” It replied with five ideas, including the standard methotrexate and azathioprine but also IVIG, Rituxan, even other biologics. Write an op note? Appeal a denied prior authorization to a payer? Write a clinic note for a complete skin exam? Check, check, check. Are you starting to think it might be the real deal, too?
Before we sell the farm though, there are significant limitations. Despite how swotty ChatGPT seems, it is not smart. That is, “it” has no idea what “it” is saying. ChatGPT is an incredibly sophisticated algorithm that has learned the probability of what word comes next in a conversation. To do so, it read the Internet. Billions (trillions?) of words make it possible to predict what is the best answer to any question. But – it’s only as good as the Internet, so there’s that. My patient who used ChatGPT has dissecting cellulitis and asked what to do for scarring alopecia. Some of the answers were reasonable, but some, such as transplanting hairs into the scarred areas, would not likely be helpful. That is unless ChatGPT knows something I don’t.
Having wasted hours of time playing with this thing rather than writing my column, I asked ChatGPT to write an article about itself in the style of Christopher Hitchens. It was nothing like his incisive and eloquent prose, but it wrote 500 words in a few seconds ending with:
“The reality is that there is no substitute for human interaction and empathy in the field of dermatology. Dermatologists must be cautious in their adoption of ChatGPT and ensure that they are not sacrificing the quality of patient care in the pursuit of efficiency and convenience.”
I’m not sure I could have said it better myself.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
, but I am starting to think it is the real deal. Just how powerful is it? Well, ChatGPT might in fact be writing this column right now. It isn’t. No really, it’s me. But if not for the few cues (“super-buzzy”) that you’ll recognize as my writing voice, there might not be any way for you to know if I wrote this or not.
It’s perfectly OK if you’ve no clue what I’m talking about. ChatGPT is an AI chatbot that burst into public view just a couple months ago. Not your parent’s chatbot, this one is capable of answering questions in conversational language. It is jaw-droppingly good. Like Google, you can type in a question and it offers you answers. Rather than giving you a list of websites and a few Wikipedia blurbs, however, ChatGPT answers your question in human-like text. It can also create content on demand. For example, I asked it to write a Valentine poem to a dermatologist, and it gave me five stanzas starting with:
Oh gentle healer of skin so fair,
Not good enough to send to my wife. But not bad.
If you ask it again, it will create a whole new one for you. Amusing, yes? What if you asked ChatGPT to explain psoriasis, or any medical condition for that matter, to a patient? The replies are quite good. Some even better than what I’m currently using for my patients. It can also offer treatment recommendations, vacation advice, and plan, with recipes, a dinner party for six with one vegan and one gluten-free couple. If you are a programmer, it can write code. Ask it for a Wordpress plugin to add to your website and your eyes will widen as you see it magically appear before you. What if you find that you just don’t like your daughter’s new boyfriend? Yep, it will write the text or email for you to help with this discussion. I’ve saved that one.
I tried “What are treatments for bullous pemphigoid that has been refractory to topical steroid, oral prednisone, and oral tetracyclines?” It replied with five ideas, including the standard methotrexate and azathioprine but also IVIG, Rituxan, even other biologics. Write an op note? Appeal a denied prior authorization to a payer? Write a clinic note for a complete skin exam? Check, check, check. Are you starting to think it might be the real deal, too?
Before we sell the farm though, there are significant limitations. Despite how swotty ChatGPT seems, it is not smart. That is, “it” has no idea what “it” is saying. ChatGPT is an incredibly sophisticated algorithm that has learned the probability of what word comes next in a conversation. To do so, it read the Internet. Billions (trillions?) of words make it possible to predict what is the best answer to any question. But – it’s only as good as the Internet, so there’s that. My patient who used ChatGPT has dissecting cellulitis and asked what to do for scarring alopecia. Some of the answers were reasonable, but some, such as transplanting hairs into the scarred areas, would not likely be helpful. That is unless ChatGPT knows something I don’t.
Having wasted hours of time playing with this thing rather than writing my column, I asked ChatGPT to write an article about itself in the style of Christopher Hitchens. It was nothing like his incisive and eloquent prose, but it wrote 500 words in a few seconds ending with:
“The reality is that there is no substitute for human interaction and empathy in the field of dermatology. Dermatologists must be cautious in their adoption of ChatGPT and ensure that they are not sacrificing the quality of patient care in the pursuit of efficiency and convenience.”
I’m not sure I could have said it better myself.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
Health plans get very poor scores for access to autoimmune drugs
Both public and private health plans score poorly when it comes to providing access to autoimmune medication, according to a report commissioned by the Autoimmune Association and Let My Doctors Decide, a national partnership of health care professionals. The analysis, published Jan. 26, found that 75% of insurers in the United States have policies that can limit coverage for Food and Drug Administration–approved medications for Crohn’s disease, lupus nephritis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.
“Choice among health plans is a hallmark of the American health insurance system, yet this analysis shows that people living with autoimmune conditions have few, if any, coverage choices that do not involve significant to severe access restrictions,” the authors wrote.
The study looked at three common utilization management policies by health plans that can limit coverage of certain medications: step therapy, formulary/tier placement, and prior authorization. To compare health plans, researchers weighted these policies using a point system. Each medication indicated for each condition was given a score of 0-4 based on access restrictions in a health plan. If a plan used step therapy, it received one point, and requiring prior authorization added an additional point. They also added points based on where a drug appeared on a plan’s formulary. A lower total score meant fewer access barriers. The numbers were then added, and each health plan received a grade of A, B, C, or F based on their average score. The datasets and analysis were provided and performed by the data analytics firm MMIT.
Nearly 9 in 10 Medicare plans received a C or worse for coverage of medication received via mail order or the pharmacy. In commercial plans, the majority of plans scored Cs or Fs for six of the seven conditions, excluding lupus nephritis, where 67% of all commercial health plans scored a B for access to these medications.
Physician-administered medications tended to receive poorer coverage than drugs received via pharmacy. Across all conditions, 65% of Medicare Advantage plans scored an F for physician-administered medication access. For both psoriasis and multiple sclerosis, at least 80% of Medicare plans earned failing scores because of these restrictions. Coverage was poorer on both commercial and health exchange plans, where across all conditions, 83% achieved failing scores. Two exceptions were the Southern and Northern California PPO plans by the Kaiser Foundation Health Plan. Out of the largest 25 health plans in the United States, these two plans earned As in coverage for physician-administered medications across all seven autoimmune conditions.
The report shows “a growing disconnect between science and health insurance benefit designs that were developed in the 1960s and 1970s,” Kenneth Thorpe, PhD, of Emory University, Atlanta, said in an interview. Insurers originally designed these benefits to prevent excessive utilization in a population of mostly acutely ill patients, he said, whereas now, 90% of healthcare spending is linked to chronic conditions. For these patients, research shows that incentivizing patients to adhere to medications results in fewer hospitalizations and, therefore, more cost savings, Thorpe noted. These plans also do not consider that there is no average patient, he said, and healthcare providers should be able to match each patient to the best treatment option for them rather than trying out other less expensive medications first. “To the extent that physicians can have the flexibility to provide medications and treatments to patients that are going to have the best clinical response, that’s better outcomes at lower cost,” Dr. Thorpe said. While research shows heterogeneity in patient outcomes with different medication, “benefit designs from the past just don’t recognize that.”
Neither America’s Health Insurance Plans nor Pharmaceutical Care Management Association responded to a request for comment.
Quardricos Driskell, executive director of Let My Doctors Decide and vice president of government relations and public policy at the Autoimmune Association, hopes the study will spur action by policy makers and health plans to improve access to medications for the people who need them. Another larger point of the report is to “uphold the sanctity of protecting the doctor and patient relationship,” he said in an interview, adding “that decisions fundamentally need to be made not by insurance plans or middleman pharmacy benefit managers, but by the provider and patient.”
Mr. Driskell and Dr. Thorpe reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Both public and private health plans score poorly when it comes to providing access to autoimmune medication, according to a report commissioned by the Autoimmune Association and Let My Doctors Decide, a national partnership of health care professionals. The analysis, published Jan. 26, found that 75% of insurers in the United States have policies that can limit coverage for Food and Drug Administration–approved medications for Crohn’s disease, lupus nephritis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.
“Choice among health plans is a hallmark of the American health insurance system, yet this analysis shows that people living with autoimmune conditions have few, if any, coverage choices that do not involve significant to severe access restrictions,” the authors wrote.
The study looked at three common utilization management policies by health plans that can limit coverage of certain medications: step therapy, formulary/tier placement, and prior authorization. To compare health plans, researchers weighted these policies using a point system. Each medication indicated for each condition was given a score of 0-4 based on access restrictions in a health plan. If a plan used step therapy, it received one point, and requiring prior authorization added an additional point. They also added points based on where a drug appeared on a plan’s formulary. A lower total score meant fewer access barriers. The numbers were then added, and each health plan received a grade of A, B, C, or F based on their average score. The datasets and analysis were provided and performed by the data analytics firm MMIT.
Nearly 9 in 10 Medicare plans received a C or worse for coverage of medication received via mail order or the pharmacy. In commercial plans, the majority of plans scored Cs or Fs for six of the seven conditions, excluding lupus nephritis, where 67% of all commercial health plans scored a B for access to these medications.
Physician-administered medications tended to receive poorer coverage than drugs received via pharmacy. Across all conditions, 65% of Medicare Advantage plans scored an F for physician-administered medication access. For both psoriasis and multiple sclerosis, at least 80% of Medicare plans earned failing scores because of these restrictions. Coverage was poorer on both commercial and health exchange plans, where across all conditions, 83% achieved failing scores. Two exceptions were the Southern and Northern California PPO plans by the Kaiser Foundation Health Plan. Out of the largest 25 health plans in the United States, these two plans earned As in coverage for physician-administered medications across all seven autoimmune conditions.
The report shows “a growing disconnect between science and health insurance benefit designs that were developed in the 1960s and 1970s,” Kenneth Thorpe, PhD, of Emory University, Atlanta, said in an interview. Insurers originally designed these benefits to prevent excessive utilization in a population of mostly acutely ill patients, he said, whereas now, 90% of healthcare spending is linked to chronic conditions. For these patients, research shows that incentivizing patients to adhere to medications results in fewer hospitalizations and, therefore, more cost savings, Thorpe noted. These plans also do not consider that there is no average patient, he said, and healthcare providers should be able to match each patient to the best treatment option for them rather than trying out other less expensive medications first. “To the extent that physicians can have the flexibility to provide medications and treatments to patients that are going to have the best clinical response, that’s better outcomes at lower cost,” Dr. Thorpe said. While research shows heterogeneity in patient outcomes with different medication, “benefit designs from the past just don’t recognize that.”
Neither America’s Health Insurance Plans nor Pharmaceutical Care Management Association responded to a request for comment.
Quardricos Driskell, executive director of Let My Doctors Decide and vice president of government relations and public policy at the Autoimmune Association, hopes the study will spur action by policy makers and health plans to improve access to medications for the people who need them. Another larger point of the report is to “uphold the sanctity of protecting the doctor and patient relationship,” he said in an interview, adding “that decisions fundamentally need to be made not by insurance plans or middleman pharmacy benefit managers, but by the provider and patient.”
Mr. Driskell and Dr. Thorpe reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Both public and private health plans score poorly when it comes to providing access to autoimmune medication, according to a report commissioned by the Autoimmune Association and Let My Doctors Decide, a national partnership of health care professionals. The analysis, published Jan. 26, found that 75% of insurers in the United States have policies that can limit coverage for Food and Drug Administration–approved medications for Crohn’s disease, lupus nephritis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.
“Choice among health plans is a hallmark of the American health insurance system, yet this analysis shows that people living with autoimmune conditions have few, if any, coverage choices that do not involve significant to severe access restrictions,” the authors wrote.
The study looked at three common utilization management policies by health plans that can limit coverage of certain medications: step therapy, formulary/tier placement, and prior authorization. To compare health plans, researchers weighted these policies using a point system. Each medication indicated for each condition was given a score of 0-4 based on access restrictions in a health plan. If a plan used step therapy, it received one point, and requiring prior authorization added an additional point. They also added points based on where a drug appeared on a plan’s formulary. A lower total score meant fewer access barriers. The numbers were then added, and each health plan received a grade of A, B, C, or F based on their average score. The datasets and analysis were provided and performed by the data analytics firm MMIT.
Nearly 9 in 10 Medicare plans received a C or worse for coverage of medication received via mail order or the pharmacy. In commercial plans, the majority of plans scored Cs or Fs for six of the seven conditions, excluding lupus nephritis, where 67% of all commercial health plans scored a B for access to these medications.
Physician-administered medications tended to receive poorer coverage than drugs received via pharmacy. Across all conditions, 65% of Medicare Advantage plans scored an F for physician-administered medication access. For both psoriasis and multiple sclerosis, at least 80% of Medicare plans earned failing scores because of these restrictions. Coverage was poorer on both commercial and health exchange plans, where across all conditions, 83% achieved failing scores. Two exceptions were the Southern and Northern California PPO plans by the Kaiser Foundation Health Plan. Out of the largest 25 health plans in the United States, these two plans earned As in coverage for physician-administered medications across all seven autoimmune conditions.
The report shows “a growing disconnect between science and health insurance benefit designs that were developed in the 1960s and 1970s,” Kenneth Thorpe, PhD, of Emory University, Atlanta, said in an interview. Insurers originally designed these benefits to prevent excessive utilization in a population of mostly acutely ill patients, he said, whereas now, 90% of healthcare spending is linked to chronic conditions. For these patients, research shows that incentivizing patients to adhere to medications results in fewer hospitalizations and, therefore, more cost savings, Thorpe noted. These plans also do not consider that there is no average patient, he said, and healthcare providers should be able to match each patient to the best treatment option for them rather than trying out other less expensive medications first. “To the extent that physicians can have the flexibility to provide medications and treatments to patients that are going to have the best clinical response, that’s better outcomes at lower cost,” Dr. Thorpe said. While research shows heterogeneity in patient outcomes with different medication, “benefit designs from the past just don’t recognize that.”
Neither America’s Health Insurance Plans nor Pharmaceutical Care Management Association responded to a request for comment.
Quardricos Driskell, executive director of Let My Doctors Decide and vice president of government relations and public policy at the Autoimmune Association, hopes the study will spur action by policy makers and health plans to improve access to medications for the people who need them. Another larger point of the report is to “uphold the sanctity of protecting the doctor and patient relationship,” he said in an interview, adding “that decisions fundamentally need to be made not by insurance plans or middleman pharmacy benefit managers, but by the provider and patient.”
Mr. Driskell and Dr. Thorpe reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Secukinumab shows benefit for hidradenitis suppurativa out to 52 weeks
results from two pivotal phase 3 clinical trials showed.
The findings build on week 16 data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety, and tolerability of the interleukin-17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS, and were presented at the 2022 annual congress of the European Academy of Dermatology and Venereology. In those studies, at 16 weeks, 42%-46% of patients achieved an HS Clinical Response (HiSCR) – the primary outcome measure in both trials. For the most recent analysis, which was published in The Lancet, investigators found that, at 52 weeks, 56.4% of patients in SUNSHINE and 65% of patients in SUNRISE who received secukinumab 300 mg every 2 weeks achieved a HiSCR, compared with 56.3% of patients in SUNSHINE and 62.2% of patients in SUNRISE who received secukinumab 300 mg every 4 weeks.
“This is great news for people with HS: it improves our knowledge about how to best treat patients today and leads us to new areas that will help us treat them even better in the future,” Alexa B. Kimball, MD, MPH, the lead investigator for both trials, said in an interview. “Dermatologists have been using biologics for decades. This data provides clinicians with information they can use to easily expand their HS management repertoire to include secukinumab.”
To date, the tumor necrosis factor inhibitor adalimumab is the only approved biologic therapy approved for the treatment of moderate-to-severe HS, in people aged 12 years and older.
The two trials were conducted in 40 countries, with SUNSHINE enrolling 541 patients, and SUNRISE enrolling 543. Patients in each study were randomized to one of three experimental arms: secukinumab 300 mg every 2 weeks after five weekly loading doses; secukinumab 300 mg every 4 weeks after five weekly loading doses; placebo dose every 2 weeks after five weekly placebo doses. The mean age was 37 years, about 55% were female, and about 76% were White (about 9% were Black and about 10% were Asian). Dr. Kimball, investigator at Beth Israel Deaconess Medical Center and professor of dermatology at Harvard Medical School, Boston, and coauthors observed that the group that received secukinumab every 4 weeks did not meet the primary endpoint in the SUNSHINE trial, but it was met in the SUNRISE trial. “Research and subgroup analyses are required and might improve our understanding of the effect of patient characteristics on treatment response and further refine the dosing recommendations for different populations,” they wrote.
In a pooled analysis, 55.2% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 2 weeks had a reduction in pain as measured by the Patient’s Global Assessment of Skin Pain Numeric Rating Scale, compared with 53% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 4 weeks. The most common adverse events up to week 16 in both trials were headache, nasopharyngitis, and hidradenitis; no deaths occurred.
“One limitation of most studies in HS is that the placebo-controlled period is short, so the data obtained after that time is harder to interpret,” Dr. Kimball said in an interview. “In my experience, optimizing treatment can take almost a year and I hope we will see longer controlled periods in future studies.” Another limitation of the studies she acknowledged was a modest imbalance with respect to disease severity between the treatment groups at baseline. “It was a little surprising that some imbalances in the characteristics of randomized subjects in different arms of the study impacted efficacy levels,” she said. “We’ll need to continue to identify how to match patients and dosing regimens to get the best results.”
According to a press release from Novartis, trial results have been submitted to regulatory authorities in Europe and the United States, and decisions are expected in 2023. If approved, secukinumab will be the first and only IL-17 inhibitor for the treatment of moderate to severe HS.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, described HS as “an extraordinarily disabling, painful, deforming condition for which we only have one [Food and Drug Administration]–approved systemic therapy, requiring us to wear our ‘off-label bandit’ name tags proudly to tackle therapeutic challenges.
“Anecdotally,” he said, “we dabble with off-label biologics indicated for psoriasis in this setting, though limitations exist ranging from lack of large-scale clinical data to the recurring theme that psoriasis dosing typically doesn’t cut it, making access to said medications even more difficult. Investigators in this study addresses both gaps very effectively, and I for one welcome the implications and hopeful regulatory impact with open arms.”
The study was funded by Novartis. Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies. Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.
results from two pivotal phase 3 clinical trials showed.
The findings build on week 16 data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety, and tolerability of the interleukin-17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS, and were presented at the 2022 annual congress of the European Academy of Dermatology and Venereology. In those studies, at 16 weeks, 42%-46% of patients achieved an HS Clinical Response (HiSCR) – the primary outcome measure in both trials. For the most recent analysis, which was published in The Lancet, investigators found that, at 52 weeks, 56.4% of patients in SUNSHINE and 65% of patients in SUNRISE who received secukinumab 300 mg every 2 weeks achieved a HiSCR, compared with 56.3% of patients in SUNSHINE and 62.2% of patients in SUNRISE who received secukinumab 300 mg every 4 weeks.
“This is great news for people with HS: it improves our knowledge about how to best treat patients today and leads us to new areas that will help us treat them even better in the future,” Alexa B. Kimball, MD, MPH, the lead investigator for both trials, said in an interview. “Dermatologists have been using biologics for decades. This data provides clinicians with information they can use to easily expand their HS management repertoire to include secukinumab.”
To date, the tumor necrosis factor inhibitor adalimumab is the only approved biologic therapy approved for the treatment of moderate-to-severe HS, in people aged 12 years and older.
The two trials were conducted in 40 countries, with SUNSHINE enrolling 541 patients, and SUNRISE enrolling 543. Patients in each study were randomized to one of three experimental arms: secukinumab 300 mg every 2 weeks after five weekly loading doses; secukinumab 300 mg every 4 weeks after five weekly loading doses; placebo dose every 2 weeks after five weekly placebo doses. The mean age was 37 years, about 55% were female, and about 76% were White (about 9% were Black and about 10% were Asian). Dr. Kimball, investigator at Beth Israel Deaconess Medical Center and professor of dermatology at Harvard Medical School, Boston, and coauthors observed that the group that received secukinumab every 4 weeks did not meet the primary endpoint in the SUNSHINE trial, but it was met in the SUNRISE trial. “Research and subgroup analyses are required and might improve our understanding of the effect of patient characteristics on treatment response and further refine the dosing recommendations for different populations,” they wrote.
In a pooled analysis, 55.2% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 2 weeks had a reduction in pain as measured by the Patient’s Global Assessment of Skin Pain Numeric Rating Scale, compared with 53% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 4 weeks. The most common adverse events up to week 16 in both trials were headache, nasopharyngitis, and hidradenitis; no deaths occurred.
“One limitation of most studies in HS is that the placebo-controlled period is short, so the data obtained after that time is harder to interpret,” Dr. Kimball said in an interview. “In my experience, optimizing treatment can take almost a year and I hope we will see longer controlled periods in future studies.” Another limitation of the studies she acknowledged was a modest imbalance with respect to disease severity between the treatment groups at baseline. “It was a little surprising that some imbalances in the characteristics of randomized subjects in different arms of the study impacted efficacy levels,” she said. “We’ll need to continue to identify how to match patients and dosing regimens to get the best results.”
According to a press release from Novartis, trial results have been submitted to regulatory authorities in Europe and the United States, and decisions are expected in 2023. If approved, secukinumab will be the first and only IL-17 inhibitor for the treatment of moderate to severe HS.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, described HS as “an extraordinarily disabling, painful, deforming condition for which we only have one [Food and Drug Administration]–approved systemic therapy, requiring us to wear our ‘off-label bandit’ name tags proudly to tackle therapeutic challenges.
“Anecdotally,” he said, “we dabble with off-label biologics indicated for psoriasis in this setting, though limitations exist ranging from lack of large-scale clinical data to the recurring theme that psoriasis dosing typically doesn’t cut it, making access to said medications even more difficult. Investigators in this study addresses both gaps very effectively, and I for one welcome the implications and hopeful regulatory impact with open arms.”
The study was funded by Novartis. Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies. Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.
results from two pivotal phase 3 clinical trials showed.
The findings build on week 16 data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety, and tolerability of the interleukin-17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS, and were presented at the 2022 annual congress of the European Academy of Dermatology and Venereology. In those studies, at 16 weeks, 42%-46% of patients achieved an HS Clinical Response (HiSCR) – the primary outcome measure in both trials. For the most recent analysis, which was published in The Lancet, investigators found that, at 52 weeks, 56.4% of patients in SUNSHINE and 65% of patients in SUNRISE who received secukinumab 300 mg every 2 weeks achieved a HiSCR, compared with 56.3% of patients in SUNSHINE and 62.2% of patients in SUNRISE who received secukinumab 300 mg every 4 weeks.
“This is great news for people with HS: it improves our knowledge about how to best treat patients today and leads us to new areas that will help us treat them even better in the future,” Alexa B. Kimball, MD, MPH, the lead investigator for both trials, said in an interview. “Dermatologists have been using biologics for decades. This data provides clinicians with information they can use to easily expand their HS management repertoire to include secukinumab.”
To date, the tumor necrosis factor inhibitor adalimumab is the only approved biologic therapy approved for the treatment of moderate-to-severe HS, in people aged 12 years and older.
The two trials were conducted in 40 countries, with SUNSHINE enrolling 541 patients, and SUNRISE enrolling 543. Patients in each study were randomized to one of three experimental arms: secukinumab 300 mg every 2 weeks after five weekly loading doses; secukinumab 300 mg every 4 weeks after five weekly loading doses; placebo dose every 2 weeks after five weekly placebo doses. The mean age was 37 years, about 55% were female, and about 76% were White (about 9% were Black and about 10% were Asian). Dr. Kimball, investigator at Beth Israel Deaconess Medical Center and professor of dermatology at Harvard Medical School, Boston, and coauthors observed that the group that received secukinumab every 4 weeks did not meet the primary endpoint in the SUNSHINE trial, but it was met in the SUNRISE trial. “Research and subgroup analyses are required and might improve our understanding of the effect of patient characteristics on treatment response and further refine the dosing recommendations for different populations,” they wrote.
In a pooled analysis, 55.2% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 2 weeks had a reduction in pain as measured by the Patient’s Global Assessment of Skin Pain Numeric Rating Scale, compared with 53% of patients from SUNSHINE and SUNRISE who received secukinumab 300 mg every 4 weeks. The most common adverse events up to week 16 in both trials were headache, nasopharyngitis, and hidradenitis; no deaths occurred.
“One limitation of most studies in HS is that the placebo-controlled period is short, so the data obtained after that time is harder to interpret,” Dr. Kimball said in an interview. “In my experience, optimizing treatment can take almost a year and I hope we will see longer controlled periods in future studies.” Another limitation of the studies she acknowledged was a modest imbalance with respect to disease severity between the treatment groups at baseline. “It was a little surprising that some imbalances in the characteristics of randomized subjects in different arms of the study impacted efficacy levels,” she said. “We’ll need to continue to identify how to match patients and dosing regimens to get the best results.”
According to a press release from Novartis, trial results have been submitted to regulatory authorities in Europe and the United States, and decisions are expected in 2023. If approved, secukinumab will be the first and only IL-17 inhibitor for the treatment of moderate to severe HS.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, described HS as “an extraordinarily disabling, painful, deforming condition for which we only have one [Food and Drug Administration]–approved systemic therapy, requiring us to wear our ‘off-label bandit’ name tags proudly to tackle therapeutic challenges.
“Anecdotally,” he said, “we dabble with off-label biologics indicated for psoriasis in this setting, though limitations exist ranging from lack of large-scale clinical data to the recurring theme that psoriasis dosing typically doesn’t cut it, making access to said medications even more difficult. Investigators in this study addresses both gaps very effectively, and I for one welcome the implications and hopeful regulatory impact with open arms.”
The study was funded by Novartis. Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies. Dr. Friedman reported financial relationships with Sanova, Pfizer, Novartis, and other companies.
FROM THE LANCET
More than 97K new cutaneous melanoma diagnoses expected in 2023
SAN DIEGO – , following cancer of the colorectal area, lung and bronchus, prostate, and breast.
“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist who practices in Macon, Ga., said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”
In 2023, the ACS estimates that about 97,610 new melanomas will be diagnosed in the United States (58,120 men and 39,490 women), and about 7,990 people are expected to die of melanoma (5,420 men and 2,570 women). In addition, ACS data from 2017-2019 project that about 2.1% of men and women will be diagnosed with cutaneous melanoma in their lifetime. To date, more than 1.3 million people in the United States live with cutaneous melanoma, and the overall 5-year survival is 93.7%.
Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due primarily to sun exposure and to changing recreational behaviors and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3% to 7% per year, “which translates into a doubling of rates every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.
While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color. Blacks present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.
Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1, and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.
The main environmental risk factor for melanoma is exposure to ultraviolet radiation. “You can break it down in terms of whether this exposure is lifetime, intermittent intense UV exposure, from the use of tanning beds, or due to sunburns during childhood,” Dr. Kent said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. Other environmental risk factors include distance from the equator, having a high socioeconomic status, being immunosuppressed, and exposure to heavy metals, insecticides, or hormones.
In a recently published study, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1,212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than were first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than were first melanomas.
In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio [HR], 6.36 vs. 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03).
Second melanomas were also more strongly associated with a history of multiple skin cancer excisions than were first melanomas (HR, 2.63 vs. 1.86; P = .05). “Interestingly, there were no differences in UV exposure between the first primary and second primary melanoma groups,” said Dr. Kent, who was not involved with the study.
He noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey (NAMCS) found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits – even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said. “We as dermatologists have work to do to help educate them.”
Dr. Kent reported having no relevant disclosures.
SAN DIEGO – , following cancer of the colorectal area, lung and bronchus, prostate, and breast.
“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist who practices in Macon, Ga., said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”
In 2023, the ACS estimates that about 97,610 new melanomas will be diagnosed in the United States (58,120 men and 39,490 women), and about 7,990 people are expected to die of melanoma (5,420 men and 2,570 women). In addition, ACS data from 2017-2019 project that about 2.1% of men and women will be diagnosed with cutaneous melanoma in their lifetime. To date, more than 1.3 million people in the United States live with cutaneous melanoma, and the overall 5-year survival is 93.7%.
Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due primarily to sun exposure and to changing recreational behaviors and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3% to 7% per year, “which translates into a doubling of rates every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.
While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color. Blacks present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.
Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1, and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.
The main environmental risk factor for melanoma is exposure to ultraviolet radiation. “You can break it down in terms of whether this exposure is lifetime, intermittent intense UV exposure, from the use of tanning beds, or due to sunburns during childhood,” Dr. Kent said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. Other environmental risk factors include distance from the equator, having a high socioeconomic status, being immunosuppressed, and exposure to heavy metals, insecticides, or hormones.
In a recently published study, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1,212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than were first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than were first melanomas.
In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio [HR], 6.36 vs. 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03).
Second melanomas were also more strongly associated with a history of multiple skin cancer excisions than were first melanomas (HR, 2.63 vs. 1.86; P = .05). “Interestingly, there were no differences in UV exposure between the first primary and second primary melanoma groups,” said Dr. Kent, who was not involved with the study.
He noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey (NAMCS) found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits – even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said. “We as dermatologists have work to do to help educate them.”
Dr. Kent reported having no relevant disclosures.
SAN DIEGO – , following cancer of the colorectal area, lung and bronchus, prostate, and breast.
“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist who practices in Macon, Ga., said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”
In 2023, the ACS estimates that about 97,610 new melanomas will be diagnosed in the United States (58,120 men and 39,490 women), and about 7,990 people are expected to die of melanoma (5,420 men and 2,570 women). In addition, ACS data from 2017-2019 project that about 2.1% of men and women will be diagnosed with cutaneous melanoma in their lifetime. To date, more than 1.3 million people in the United States live with cutaneous melanoma, and the overall 5-year survival is 93.7%.
Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due primarily to sun exposure and to changing recreational behaviors and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3% to 7% per year, “which translates into a doubling of rates every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.
While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color. Blacks present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.
Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1, and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.
The main environmental risk factor for melanoma is exposure to ultraviolet radiation. “You can break it down in terms of whether this exposure is lifetime, intermittent intense UV exposure, from the use of tanning beds, or due to sunburns during childhood,” Dr. Kent said at the meeting, which was hosted by Scripps MD Anderson Cancer Center. Other environmental risk factors include distance from the equator, having a high socioeconomic status, being immunosuppressed, and exposure to heavy metals, insecticides, or hormones.
In a recently published study, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1,212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than were first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than were first melanomas.
In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio [HR], 6.36 vs. 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03).
Second melanomas were also more strongly associated with a history of multiple skin cancer excisions than were first melanomas (HR, 2.63 vs. 1.86; P = .05). “Interestingly, there were no differences in UV exposure between the first primary and second primary melanoma groups,” said Dr. Kent, who was not involved with the study.
He noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey (NAMCS) found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits – even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said. “We as dermatologists have work to do to help educate them.”
Dr. Kent reported having no relevant disclosures.
AT MELANOMA 2023
Notalgia paresthetica: Difelikefalin helps upper-back itch, but with side effects
from a randomized, double-blinded placebo-controlled trial suggest.
However, side effects were significant and caused 19% in the intervention group to discontinue the trial versus 6% in the placebo group.
Results of the study were published online in the New England Journal of Medicine.
There is currently no treatment approved by the U.S. Food and Drug Administration for the common condition, which typically causes itch in the hard-to-reach area between the shoulder blades or mid-back.
Drug reduced moderate to severe itch
Difelikefalin – a selective kappa-opioid receptor agonist – is FDA approved only as an injection for treating moderate to severe itch from chronic kidney disease in adults undergoing hemodialysis, and is marketed as Korsuva for that indication.
However, in a new trial, led by Brian S. Kim, MD, professor of dermatology and vice chair of research at the Icahn School of Medicine at Mount Sinai, New York, the drug gave moderate relief to patients with notalgia paresthetica who had moderate to severe itch.
Patients were randomly assigned 1:1 to receive oral difelikefalin 2 mg or a placebo twice daily for 8 weeks. The primary outcome was change in the weekly average of the daily 0-10 Worst Itch Numeric Rating Scale, for which 0 is “no itch” and 10 is “worst itch imaginable.”
Secondary clinical outcomes were itch-related quality-of-life and itch-related sleep measures.
The study included 126 patients; 62 received difelikefalin and 63 received placebo. One patient assigned to the difelikefalin group withdrew consent before the first dose.
The average baseline score on the Worst Itch scale was 7.6 (severe itch) in each group. Mean scores in the difelikefalin dropped by 4 points versus 2.4 points in the placebo group (95% confidence interval, −2.6 to −0.6; P = .001).
Difelikefalin did not help with sleep disturbance, compared with placebo, “except possibly in patients with impaired sleep at baseline,” the authors write. “Larger and longer trials are required to determine the effect and risks of difelikefalin treatment in this disorder.”
In a Mount Sinai press release, Dr. Kim, who is also director of the Lebwohl Center for Neuroinflammation and Sensation at Mount Sinai, called the team’s findings “encouraging.”
“The encouraging results achieved in this trial could reenergize the field and mark an important step toward improving symptoms of itch for patients with notalgia paresthetica,” he said.
Side effects ‘worrisome’
The main side effects reported included headaches, dizziness, constipation and increased urine output.
Shawn Kwatra, MD, director of the Johns Hopkins Itch Center, Baltimore, told this news organization that dizziness was “especially worrisome,” noting the average age of participants in the trial was 59-60 years. “We are very concerned about folks having falls or hip fractures,” he said.
“Things we use more commonly are topical steroids, topical capsaicin, the capsaicin patch, muscle strengthening, and gabapentin,” Dr. Kwatra said. “Off-label we use botulinum toxin (Botox) as well. I’m able to control” almost all of my notalgia paresthetica patients, he added.
In his view, for this type of drug, he said, “the right home for it is more for a generalized neuropathic pruritus or nociplastic itch vs. something very localized which is more amenable to topical therapies.”
He said that the associated central nervous system effects, such as dizziness and headache, “would limit therapeutic use to only the most severe cases in my mind.”
The trial was funded by Cara Therapeutics, manufacturer of difelikefalin.
Dr. Kim and coauthor Mark Lebwohl, MD, are paid consultants/advisers to Cara Therapeutics. Other coauthors also reported ties to Cara. Dr. Kwatra previously had done consulting work for Cara Therapeutics and is an advisory board member/consultant for AbbVie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Castle Biosciences, Celldex Therapeutics, Galderma, Genzada Pharmaceuticals, Incyte Corporation, Johnson & Johnson, Leo Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi and has served as an investigator for Galderma, Incyte, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
from a randomized, double-blinded placebo-controlled trial suggest.
However, side effects were significant and caused 19% in the intervention group to discontinue the trial versus 6% in the placebo group.
Results of the study were published online in the New England Journal of Medicine.
There is currently no treatment approved by the U.S. Food and Drug Administration for the common condition, which typically causes itch in the hard-to-reach area between the shoulder blades or mid-back.
Drug reduced moderate to severe itch
Difelikefalin – a selective kappa-opioid receptor agonist – is FDA approved only as an injection for treating moderate to severe itch from chronic kidney disease in adults undergoing hemodialysis, and is marketed as Korsuva for that indication.
However, in a new trial, led by Brian S. Kim, MD, professor of dermatology and vice chair of research at the Icahn School of Medicine at Mount Sinai, New York, the drug gave moderate relief to patients with notalgia paresthetica who had moderate to severe itch.
Patients were randomly assigned 1:1 to receive oral difelikefalin 2 mg or a placebo twice daily for 8 weeks. The primary outcome was change in the weekly average of the daily 0-10 Worst Itch Numeric Rating Scale, for which 0 is “no itch” and 10 is “worst itch imaginable.”
Secondary clinical outcomes were itch-related quality-of-life and itch-related sleep measures.
The study included 126 patients; 62 received difelikefalin and 63 received placebo. One patient assigned to the difelikefalin group withdrew consent before the first dose.
The average baseline score on the Worst Itch scale was 7.6 (severe itch) in each group. Mean scores in the difelikefalin dropped by 4 points versus 2.4 points in the placebo group (95% confidence interval, −2.6 to −0.6; P = .001).
Difelikefalin did not help with sleep disturbance, compared with placebo, “except possibly in patients with impaired sleep at baseline,” the authors write. “Larger and longer trials are required to determine the effect and risks of difelikefalin treatment in this disorder.”
In a Mount Sinai press release, Dr. Kim, who is also director of the Lebwohl Center for Neuroinflammation and Sensation at Mount Sinai, called the team’s findings “encouraging.”
“The encouraging results achieved in this trial could reenergize the field and mark an important step toward improving symptoms of itch for patients with notalgia paresthetica,” he said.
Side effects ‘worrisome’
The main side effects reported included headaches, dizziness, constipation and increased urine output.
Shawn Kwatra, MD, director of the Johns Hopkins Itch Center, Baltimore, told this news organization that dizziness was “especially worrisome,” noting the average age of participants in the trial was 59-60 years. “We are very concerned about folks having falls or hip fractures,” he said.
“Things we use more commonly are topical steroids, topical capsaicin, the capsaicin patch, muscle strengthening, and gabapentin,” Dr. Kwatra said. “Off-label we use botulinum toxin (Botox) as well. I’m able to control” almost all of my notalgia paresthetica patients, he added.
In his view, for this type of drug, he said, “the right home for it is more for a generalized neuropathic pruritus or nociplastic itch vs. something very localized which is more amenable to topical therapies.”
He said that the associated central nervous system effects, such as dizziness and headache, “would limit therapeutic use to only the most severe cases in my mind.”
The trial was funded by Cara Therapeutics, manufacturer of difelikefalin.
Dr. Kim and coauthor Mark Lebwohl, MD, are paid consultants/advisers to Cara Therapeutics. Other coauthors also reported ties to Cara. Dr. Kwatra previously had done consulting work for Cara Therapeutics and is an advisory board member/consultant for AbbVie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Castle Biosciences, Celldex Therapeutics, Galderma, Genzada Pharmaceuticals, Incyte Corporation, Johnson & Johnson, Leo Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi and has served as an investigator for Galderma, Incyte, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
from a randomized, double-blinded placebo-controlled trial suggest.
However, side effects were significant and caused 19% in the intervention group to discontinue the trial versus 6% in the placebo group.
Results of the study were published online in the New England Journal of Medicine.
There is currently no treatment approved by the U.S. Food and Drug Administration for the common condition, which typically causes itch in the hard-to-reach area between the shoulder blades or mid-back.
Drug reduced moderate to severe itch
Difelikefalin – a selective kappa-opioid receptor agonist – is FDA approved only as an injection for treating moderate to severe itch from chronic kidney disease in adults undergoing hemodialysis, and is marketed as Korsuva for that indication.
However, in a new trial, led by Brian S. Kim, MD, professor of dermatology and vice chair of research at the Icahn School of Medicine at Mount Sinai, New York, the drug gave moderate relief to patients with notalgia paresthetica who had moderate to severe itch.
Patients were randomly assigned 1:1 to receive oral difelikefalin 2 mg or a placebo twice daily for 8 weeks. The primary outcome was change in the weekly average of the daily 0-10 Worst Itch Numeric Rating Scale, for which 0 is “no itch” and 10 is “worst itch imaginable.”
Secondary clinical outcomes were itch-related quality-of-life and itch-related sleep measures.
The study included 126 patients; 62 received difelikefalin and 63 received placebo. One patient assigned to the difelikefalin group withdrew consent before the first dose.
The average baseline score on the Worst Itch scale was 7.6 (severe itch) in each group. Mean scores in the difelikefalin dropped by 4 points versus 2.4 points in the placebo group (95% confidence interval, −2.6 to −0.6; P = .001).
Difelikefalin did not help with sleep disturbance, compared with placebo, “except possibly in patients with impaired sleep at baseline,” the authors write. “Larger and longer trials are required to determine the effect and risks of difelikefalin treatment in this disorder.”
In a Mount Sinai press release, Dr. Kim, who is also director of the Lebwohl Center for Neuroinflammation and Sensation at Mount Sinai, called the team’s findings “encouraging.”
“The encouraging results achieved in this trial could reenergize the field and mark an important step toward improving symptoms of itch for patients with notalgia paresthetica,” he said.
Side effects ‘worrisome’
The main side effects reported included headaches, dizziness, constipation and increased urine output.
Shawn Kwatra, MD, director of the Johns Hopkins Itch Center, Baltimore, told this news organization that dizziness was “especially worrisome,” noting the average age of participants in the trial was 59-60 years. “We are very concerned about folks having falls or hip fractures,” he said.
“Things we use more commonly are topical steroids, topical capsaicin, the capsaicin patch, muscle strengthening, and gabapentin,” Dr. Kwatra said. “Off-label we use botulinum toxin (Botox) as well. I’m able to control” almost all of my notalgia paresthetica patients, he added.
In his view, for this type of drug, he said, “the right home for it is more for a generalized neuropathic pruritus or nociplastic itch vs. something very localized which is more amenable to topical therapies.”
He said that the associated central nervous system effects, such as dizziness and headache, “would limit therapeutic use to only the most severe cases in my mind.”
The trial was funded by Cara Therapeutics, manufacturer of difelikefalin.
Dr. Kim and coauthor Mark Lebwohl, MD, are paid consultants/advisers to Cara Therapeutics. Other coauthors also reported ties to Cara. Dr. Kwatra previously had done consulting work for Cara Therapeutics and is an advisory board member/consultant for AbbVie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Castle Biosciences, Celldex Therapeutics, Galderma, Genzada Pharmaceuticals, Incyte Corporation, Johnson & Johnson, Leo Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi and has served as an investigator for Galderma, Incyte, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Isothiazolinone contact allergy up in North America, down in Europe
, a trend that is likely driven by regulatory differences, a retrospective cohort study suggests.
“Between 2009 to 2018, the global burden of isothiazolinone allergy showed divergent trends between North American and European countries,” lead study author Margo J. Reeder, MD, of the University of Wisconsin in Madison and her colleagues write. The study was published online in JAMA Dermatology.
Isothiazolinone contact allergy peaked in Europe in 2013-2014 before gradually decreasing, they found. The prevalence of isothiazolinone allergy steadily increased in North America during the study period. “Earlier and more stringent regulation of MI [methylisothiazolinone] in Europe is associated with these divergent trends,” they write.
Common ingredients worldwide
Isothiazolinone preservatives, which are added to personal and industrial products, cause allergic contact dermatitis worldwide, the authors write. The preservatives are found in a wide range of leave-on and rinse-off water-based personal care products, such as shampoo and other hair products, dishwashing liquid, face cream, body lotion, shower gel, liquid soap, and wet wipes, as well as in water-based paint.
A mixture of methylchloroisothiazolinone (MCI) and MI has been used to prevent microbial growth in products since the 1980s. In 2005, U.S. and European regulators approved MI alone at higher concentrations as a preservative in personal care products. Coupled with consumer concerns about other preservatives, such as parabens (a rare allergen), use of MI in personal care products increased, the authors write.
Subsequently, researchers reported a global increase in the prevalence of contact allergy to isothiazolinones, the authors write. Regulatory restrictions on MI in personal care products were implemented in 2013 in Europe and in 2015 in Canada but not in the United States.
Patch test data reveal latest trends
To compare prevalence trends of allergic contact allergy to MI and sensitization to the MCI/MI mixture in North America and in Europe, Dr. Reeder and her colleagues compared the prevalence of positive patch test reactions to MCI/MI and to MI alone in North America and in Europe between 2009 and 2018.
They analyzed data from the North American Contact Dermatitis Group (NACDG), the European Surveillance System on Contact Allergies (ESSCA), and the Information Network of Departments of Dermatology (IVDK) in 2-year intervals. The data came from patients who had been patch tested at referral patch test clinics in North America and Europe.
Over the decade, the study sites conducted patch testing for 226,161 patients for MCI/MI and 118,779 for MI. Most data came from Europe. The researchers found the following:
- In Europe, isothiazolinone allergy peaked in 2013 and 2014; MCI/MI positivity reached 7.6% (ESSCA) and 5.4% (IVDK) before decreasing to 4.4% (ESSCA) and 3.2% (IVDK) in 2017-2018.
- In North America, MCI/MI positivity rose steadily from 2.5% in 2009-2010 to 10.8% in 2017-2018.
- In Europe, there were 5.5% (ESSCA) and 3.4% (IVDK) positive reactions to MI, compared with 15% (NACDG) in North America in 2017-2018.
Divergent contact allergy trends linked to regulatory approaches
The downward trend of isothiazolinone allergy in Europe after its peak in 2013 and 2014 may have been due in part, the authors explain, to a memo released in 2013 by Cosmetics Europe after it and the European Society of Contact Dermatitis reviewed reports of increased contact allergy to MI. The memo urged companies to remove MI from leave-on products.
Later that year, the European Union’s Scientific Committee on Consumer Safety advised omitting MI from leave-on consumer personal care products and moved to restrict the ingredient in rinse-off products to less than 15 ppm. The recommendation took effect in 2015.
That year, Canada banned the use of MCI/MI in leave-on products but allowed MI alone in leave-on products until 2018. The total concentration of MI and MCI in wash-off products was limited to less than 15 ppm.
The authors add that, to their knowledge, the U.S. government does not restrict the use of MCI/MI or MI.
Policy implications for contact allergy
MI is still widely used in “countless products,” including shampoos, skin cleansers, dishwashing and laundry detergents, paints, and adhesives, Daniel W. Shaw, MD, associate professor of dermatology at the University of California, San Diego, told this news organization by email.
“Exact figures between the U.S. and Europe are difficult to compare due to differing patch test concentrations, but the overall trends strongly suggest that stricter and earlier regulation in Europe resulted in lower MI allergy prevalence there than in the U.S.,” added Dr. Shaw, who was not involved in the study.
Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University in Winston-Salem, N.C., said by email that accurate information on allergic reaction prevalence is difficult to find.
“The NACDG, ESSCA, and IVDK databases may contain the best data available, but the data depend on people who get patch tested and are not directly informative of the allergy rates in the general population,” added Dr. Feldman, who was not involved in the study.
“The great majority of people in the population may not be allergic,” he said. “For those with itchy rashes, getting patch tested or avoiding products with preservatives may be prudent. Broad regulations, however, should consider the overall risks and benefits in the population, and this particular study does not fully capture those issues.”
“This study shows that government regulations are important to limit consumer exposure to common allergens, especially to the concentrations used in personal care products,” Kelly Tyler, MD, associate professor of dermatology at the Ohio State University Wexner Medical Center in Columbus, noted by email. She was not involved in the study.
She advised clinicians to ask their patients who may have allergic contact dermatitis whether they have been exposed to products containing these compounds.
“All personal care products in the store contain preservatives, and their maximum concentrations should be limited,” she advised. “The Expert Panel for Cosmetic Ingredient Safety should establish stricter guidelines for MI use in personal care products, especially given the findings of this study.”
Has MI contact allergy in North America peaked?
“In the U.S., MI has not been banned from leave-on skin-care products, but recently, its use has markedly decreased,” Dr. Shaw commented. “Hopefully, the prevalence of MI contact allergy will also begin to decrease.”
New evidence is promising. In a related study published online in Dermatology, Joel G. DeKoven, MD, MHSc, FRCPC, of the University of Toronto and his colleagues reported the NACDG 2019-2020 patch test results for MI in North America. They found that 13.8% of patients tested positive for MI.
“For the first time, MI positivity did not increase between reporting periods,” they conclude. “The epidemic of MI contact allergy in North America may have reached a plateau.”
Information regarding funding for the study was not provided. Dr. Reeder has financial relationships with the American Contact Dermatitis Society and a publishing company. Several coauthors have financial relationships with the pharmaceutical industry. Dr. Tyler, Dr. Shaw, and Dr. Feldman report no relevant financial relationship.
A version of this article first appeared on Medscape.com.
, a trend that is likely driven by regulatory differences, a retrospective cohort study suggests.
“Between 2009 to 2018, the global burden of isothiazolinone allergy showed divergent trends between North American and European countries,” lead study author Margo J. Reeder, MD, of the University of Wisconsin in Madison and her colleagues write. The study was published online in JAMA Dermatology.
Isothiazolinone contact allergy peaked in Europe in 2013-2014 before gradually decreasing, they found. The prevalence of isothiazolinone allergy steadily increased in North America during the study period. “Earlier and more stringent regulation of MI [methylisothiazolinone] in Europe is associated with these divergent trends,” they write.
Common ingredients worldwide
Isothiazolinone preservatives, which are added to personal and industrial products, cause allergic contact dermatitis worldwide, the authors write. The preservatives are found in a wide range of leave-on and rinse-off water-based personal care products, such as shampoo and other hair products, dishwashing liquid, face cream, body lotion, shower gel, liquid soap, and wet wipes, as well as in water-based paint.
A mixture of methylchloroisothiazolinone (MCI) and MI has been used to prevent microbial growth in products since the 1980s. In 2005, U.S. and European regulators approved MI alone at higher concentrations as a preservative in personal care products. Coupled with consumer concerns about other preservatives, such as parabens (a rare allergen), use of MI in personal care products increased, the authors write.
Subsequently, researchers reported a global increase in the prevalence of contact allergy to isothiazolinones, the authors write. Regulatory restrictions on MI in personal care products were implemented in 2013 in Europe and in 2015 in Canada but not in the United States.
Patch test data reveal latest trends
To compare prevalence trends of allergic contact allergy to MI and sensitization to the MCI/MI mixture in North America and in Europe, Dr. Reeder and her colleagues compared the prevalence of positive patch test reactions to MCI/MI and to MI alone in North America and in Europe between 2009 and 2018.
They analyzed data from the North American Contact Dermatitis Group (NACDG), the European Surveillance System on Contact Allergies (ESSCA), and the Information Network of Departments of Dermatology (IVDK) in 2-year intervals. The data came from patients who had been patch tested at referral patch test clinics in North America and Europe.
Over the decade, the study sites conducted patch testing for 226,161 patients for MCI/MI and 118,779 for MI. Most data came from Europe. The researchers found the following:
- In Europe, isothiazolinone allergy peaked in 2013 and 2014; MCI/MI positivity reached 7.6% (ESSCA) and 5.4% (IVDK) before decreasing to 4.4% (ESSCA) and 3.2% (IVDK) in 2017-2018.
- In North America, MCI/MI positivity rose steadily from 2.5% in 2009-2010 to 10.8% in 2017-2018.
- In Europe, there were 5.5% (ESSCA) and 3.4% (IVDK) positive reactions to MI, compared with 15% (NACDG) in North America in 2017-2018.
Divergent contact allergy trends linked to regulatory approaches
The downward trend of isothiazolinone allergy in Europe after its peak in 2013 and 2014 may have been due in part, the authors explain, to a memo released in 2013 by Cosmetics Europe after it and the European Society of Contact Dermatitis reviewed reports of increased contact allergy to MI. The memo urged companies to remove MI from leave-on products.
Later that year, the European Union’s Scientific Committee on Consumer Safety advised omitting MI from leave-on consumer personal care products and moved to restrict the ingredient in rinse-off products to less than 15 ppm. The recommendation took effect in 2015.
That year, Canada banned the use of MCI/MI in leave-on products but allowed MI alone in leave-on products until 2018. The total concentration of MI and MCI in wash-off products was limited to less than 15 ppm.
The authors add that, to their knowledge, the U.S. government does not restrict the use of MCI/MI or MI.
Policy implications for contact allergy
MI is still widely used in “countless products,” including shampoos, skin cleansers, dishwashing and laundry detergents, paints, and adhesives, Daniel W. Shaw, MD, associate professor of dermatology at the University of California, San Diego, told this news organization by email.
“Exact figures between the U.S. and Europe are difficult to compare due to differing patch test concentrations, but the overall trends strongly suggest that stricter and earlier regulation in Europe resulted in lower MI allergy prevalence there than in the U.S.,” added Dr. Shaw, who was not involved in the study.
Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University in Winston-Salem, N.C., said by email that accurate information on allergic reaction prevalence is difficult to find.
“The NACDG, ESSCA, and IVDK databases may contain the best data available, but the data depend on people who get patch tested and are not directly informative of the allergy rates in the general population,” added Dr. Feldman, who was not involved in the study.
“The great majority of people in the population may not be allergic,” he said. “For those with itchy rashes, getting patch tested or avoiding products with preservatives may be prudent. Broad regulations, however, should consider the overall risks and benefits in the population, and this particular study does not fully capture those issues.”
“This study shows that government regulations are important to limit consumer exposure to common allergens, especially to the concentrations used in personal care products,” Kelly Tyler, MD, associate professor of dermatology at the Ohio State University Wexner Medical Center in Columbus, noted by email. She was not involved in the study.
She advised clinicians to ask their patients who may have allergic contact dermatitis whether they have been exposed to products containing these compounds.
“All personal care products in the store contain preservatives, and their maximum concentrations should be limited,” she advised. “The Expert Panel for Cosmetic Ingredient Safety should establish stricter guidelines for MI use in personal care products, especially given the findings of this study.”
Has MI contact allergy in North America peaked?
“In the U.S., MI has not been banned from leave-on skin-care products, but recently, its use has markedly decreased,” Dr. Shaw commented. “Hopefully, the prevalence of MI contact allergy will also begin to decrease.”
New evidence is promising. In a related study published online in Dermatology, Joel G. DeKoven, MD, MHSc, FRCPC, of the University of Toronto and his colleagues reported the NACDG 2019-2020 patch test results for MI in North America. They found that 13.8% of patients tested positive for MI.
“For the first time, MI positivity did not increase between reporting periods,” they conclude. “The epidemic of MI contact allergy in North America may have reached a plateau.”
Information regarding funding for the study was not provided. Dr. Reeder has financial relationships with the American Contact Dermatitis Society and a publishing company. Several coauthors have financial relationships with the pharmaceutical industry. Dr. Tyler, Dr. Shaw, and Dr. Feldman report no relevant financial relationship.
A version of this article first appeared on Medscape.com.
, a trend that is likely driven by regulatory differences, a retrospective cohort study suggests.
“Between 2009 to 2018, the global burden of isothiazolinone allergy showed divergent trends between North American and European countries,” lead study author Margo J. Reeder, MD, of the University of Wisconsin in Madison and her colleagues write. The study was published online in JAMA Dermatology.
Isothiazolinone contact allergy peaked in Europe in 2013-2014 before gradually decreasing, they found. The prevalence of isothiazolinone allergy steadily increased in North America during the study period. “Earlier and more stringent regulation of MI [methylisothiazolinone] in Europe is associated with these divergent trends,” they write.
Common ingredients worldwide
Isothiazolinone preservatives, which are added to personal and industrial products, cause allergic contact dermatitis worldwide, the authors write. The preservatives are found in a wide range of leave-on and rinse-off water-based personal care products, such as shampoo and other hair products, dishwashing liquid, face cream, body lotion, shower gel, liquid soap, and wet wipes, as well as in water-based paint.
A mixture of methylchloroisothiazolinone (MCI) and MI has been used to prevent microbial growth in products since the 1980s. In 2005, U.S. and European regulators approved MI alone at higher concentrations as a preservative in personal care products. Coupled with consumer concerns about other preservatives, such as parabens (a rare allergen), use of MI in personal care products increased, the authors write.
Subsequently, researchers reported a global increase in the prevalence of contact allergy to isothiazolinones, the authors write. Regulatory restrictions on MI in personal care products were implemented in 2013 in Europe and in 2015 in Canada but not in the United States.
Patch test data reveal latest trends
To compare prevalence trends of allergic contact allergy to MI and sensitization to the MCI/MI mixture in North America and in Europe, Dr. Reeder and her colleagues compared the prevalence of positive patch test reactions to MCI/MI and to MI alone in North America and in Europe between 2009 and 2018.
They analyzed data from the North American Contact Dermatitis Group (NACDG), the European Surveillance System on Contact Allergies (ESSCA), and the Information Network of Departments of Dermatology (IVDK) in 2-year intervals. The data came from patients who had been patch tested at referral patch test clinics in North America and Europe.
Over the decade, the study sites conducted patch testing for 226,161 patients for MCI/MI and 118,779 for MI. Most data came from Europe. The researchers found the following:
- In Europe, isothiazolinone allergy peaked in 2013 and 2014; MCI/MI positivity reached 7.6% (ESSCA) and 5.4% (IVDK) before decreasing to 4.4% (ESSCA) and 3.2% (IVDK) in 2017-2018.
- In North America, MCI/MI positivity rose steadily from 2.5% in 2009-2010 to 10.8% in 2017-2018.
- In Europe, there were 5.5% (ESSCA) and 3.4% (IVDK) positive reactions to MI, compared with 15% (NACDG) in North America in 2017-2018.
Divergent contact allergy trends linked to regulatory approaches
The downward trend of isothiazolinone allergy in Europe after its peak in 2013 and 2014 may have been due in part, the authors explain, to a memo released in 2013 by Cosmetics Europe after it and the European Society of Contact Dermatitis reviewed reports of increased contact allergy to MI. The memo urged companies to remove MI from leave-on products.
Later that year, the European Union’s Scientific Committee on Consumer Safety advised omitting MI from leave-on consumer personal care products and moved to restrict the ingredient in rinse-off products to less than 15 ppm. The recommendation took effect in 2015.
That year, Canada banned the use of MCI/MI in leave-on products but allowed MI alone in leave-on products until 2018. The total concentration of MI and MCI in wash-off products was limited to less than 15 ppm.
The authors add that, to their knowledge, the U.S. government does not restrict the use of MCI/MI or MI.
Policy implications for contact allergy
MI is still widely used in “countless products,” including shampoos, skin cleansers, dishwashing and laundry detergents, paints, and adhesives, Daniel W. Shaw, MD, associate professor of dermatology at the University of California, San Diego, told this news organization by email.
“Exact figures between the U.S. and Europe are difficult to compare due to differing patch test concentrations, but the overall trends strongly suggest that stricter and earlier regulation in Europe resulted in lower MI allergy prevalence there than in the U.S.,” added Dr. Shaw, who was not involved in the study.
Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University in Winston-Salem, N.C., said by email that accurate information on allergic reaction prevalence is difficult to find.
“The NACDG, ESSCA, and IVDK databases may contain the best data available, but the data depend on people who get patch tested and are not directly informative of the allergy rates in the general population,” added Dr. Feldman, who was not involved in the study.
“The great majority of people in the population may not be allergic,” he said. “For those with itchy rashes, getting patch tested or avoiding products with preservatives may be prudent. Broad regulations, however, should consider the overall risks and benefits in the population, and this particular study does not fully capture those issues.”
“This study shows that government regulations are important to limit consumer exposure to common allergens, especially to the concentrations used in personal care products,” Kelly Tyler, MD, associate professor of dermatology at the Ohio State University Wexner Medical Center in Columbus, noted by email. She was not involved in the study.
She advised clinicians to ask their patients who may have allergic contact dermatitis whether they have been exposed to products containing these compounds.
“All personal care products in the store contain preservatives, and their maximum concentrations should be limited,” she advised. “The Expert Panel for Cosmetic Ingredient Safety should establish stricter guidelines for MI use in personal care products, especially given the findings of this study.”
Has MI contact allergy in North America peaked?
“In the U.S., MI has not been banned from leave-on skin-care products, but recently, its use has markedly decreased,” Dr. Shaw commented. “Hopefully, the prevalence of MI contact allergy will also begin to decrease.”
New evidence is promising. In a related study published online in Dermatology, Joel G. DeKoven, MD, MHSc, FRCPC, of the University of Toronto and his colleagues reported the NACDG 2019-2020 patch test results for MI in North America. They found that 13.8% of patients tested positive for MI.
“For the first time, MI positivity did not increase between reporting periods,” they conclude. “The epidemic of MI contact allergy in North America may have reached a plateau.”
Information regarding funding for the study was not provided. Dr. Reeder has financial relationships with the American Contact Dermatitis Society and a publishing company. Several coauthors have financial relationships with the pharmaceutical industry. Dr. Tyler, Dr. Shaw, and Dr. Feldman report no relevant financial relationship.
A version of this article first appeared on Medscape.com.
An 11-year-old boy presents with small itchy bumps on the wrists, face, arms, and legs
The patient was diagnosed with lichen nitidus, given the characteristic clinical presentation.
Lichen nitidus is a rare chronic inflammatory condition of the skin that most commonly presents in children and young adults and does not seem to be restricted to any sex or race. The classic lesions are described as asymptomatic to slightly pruritic, small (1 mm), skin-colored to hypopigmented flat-topped papules.
Koebner phenomenon is usually seen in which the skin lesions appear in areas of traumatized healthy skin. The extremities, abdomen, chest, and penis are common locations for the lesions to occur. Rarely, the oral mucosa or nails can be involved. It has been described in patients with a diagnosis of Crohn’s disease, Niemann-Pick disease, Down syndrome, and HIV. The rare, generalized purpuric variant has been reported in a few cases associated with interferon and ribavirin treatment for hepatitis C infection and nivolumab treatment for cancer. The pathophysiology of lichen nitidus is unknown.
Lichen nitidus can occur in the presence of other skin conditions like lichen planus, atopic dermatitis, vitiligo, erythema nodosum, and lichen spinulosus. Histopathologic characteristics of lichen nitidus are described as a “ball and claw” of epidermal rete around a lymphohistiocytic infiltrate. Parakeratosis overlying epidermal atrophy and focal basal liquefaction degeneration is also seen.
The differential diagnosis of lichen nitidus includes flat warts, which can present as clusters of small flat-topped papules that can show a pseudo-Koebner phenomenon (where the virus is seeded in traumatized skin). The morphological difference between the condition is that lichen nitidus lesions are usually monomorphic, compared with flat warts, which usually present with different sizes and shapes.
Patients with a history of allergic contact dermatitis may present with a generalized monomorphic eruption of skin-colored papules (known as ID reaction) that can sometimes be very similar to lichen nitidus. Allergic contact dermatitis tends to respond fairly quickly to topical or systemic corticosteroids, unlike lichen nitidus. There are a few reports that consider lichen nitidus to be a variant of lichen planus, although they have different histopathologic findings. Lichen planus lesions are described as polygonal, pruritic, purple to pink papules most commonly seen on the wrists, lower back, and ankles. Lichen planus can be seen in patients with hepatitis C and may also occur secondary to medication.
Milia are small keratin cysts on the skin that are commonly seen in babies as primary milia and can be seen in older children secondary to trauma (commonly on the eyelids) or medications. Given their size and monomorphic appearance, they can sometimes be confused with lichen nitidus.
Lichen nitidus is often asymptomatic and the lesions resolve within a few months to years. Topical corticosteroids can be helpful to alleviate the symptoms in patients who present with pruritus. In more persistent and generalized cases, phototherapy, systemic corticosteroids, acitretin, isotretinoin, or cyclosporine can be considered.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
Chu J and Lam JM. CMAJ. 2014 Dec 9;186(18):E688.
Lestringant G et al. Dermatology 1996;192:171-3.
Peterson JA et al. Proc (Bayl Univ Med Cent). 2021 Aug 25;35(1):70-2.
Schwartz C and Goodman MB. “Lichen nitidus,” in StatPearls. Treasure Island, Fla.: StatPearls Publishing, 2022.
The patient was diagnosed with lichen nitidus, given the characteristic clinical presentation.
Lichen nitidus is a rare chronic inflammatory condition of the skin that most commonly presents in children and young adults and does not seem to be restricted to any sex or race. The classic lesions are described as asymptomatic to slightly pruritic, small (1 mm), skin-colored to hypopigmented flat-topped papules.
Koebner phenomenon is usually seen in which the skin lesions appear in areas of traumatized healthy skin. The extremities, abdomen, chest, and penis are common locations for the lesions to occur. Rarely, the oral mucosa or nails can be involved. It has been described in patients with a diagnosis of Crohn’s disease, Niemann-Pick disease, Down syndrome, and HIV. The rare, generalized purpuric variant has been reported in a few cases associated with interferon and ribavirin treatment for hepatitis C infection and nivolumab treatment for cancer. The pathophysiology of lichen nitidus is unknown.
Lichen nitidus can occur in the presence of other skin conditions like lichen planus, atopic dermatitis, vitiligo, erythema nodosum, and lichen spinulosus. Histopathologic characteristics of lichen nitidus are described as a “ball and claw” of epidermal rete around a lymphohistiocytic infiltrate. Parakeratosis overlying epidermal atrophy and focal basal liquefaction degeneration is also seen.
The differential diagnosis of lichen nitidus includes flat warts, which can present as clusters of small flat-topped papules that can show a pseudo-Koebner phenomenon (where the virus is seeded in traumatized skin). The morphological difference between the condition is that lichen nitidus lesions are usually monomorphic, compared with flat warts, which usually present with different sizes and shapes.
Patients with a history of allergic contact dermatitis may present with a generalized monomorphic eruption of skin-colored papules (known as ID reaction) that can sometimes be very similar to lichen nitidus. Allergic contact dermatitis tends to respond fairly quickly to topical or systemic corticosteroids, unlike lichen nitidus. There are a few reports that consider lichen nitidus to be a variant of lichen planus, although they have different histopathologic findings. Lichen planus lesions are described as polygonal, pruritic, purple to pink papules most commonly seen on the wrists, lower back, and ankles. Lichen planus can be seen in patients with hepatitis C and may also occur secondary to medication.
Milia are small keratin cysts on the skin that are commonly seen in babies as primary milia and can be seen in older children secondary to trauma (commonly on the eyelids) or medications. Given their size and monomorphic appearance, they can sometimes be confused with lichen nitidus.
Lichen nitidus is often asymptomatic and the lesions resolve within a few months to years. Topical corticosteroids can be helpful to alleviate the symptoms in patients who present with pruritus. In more persistent and generalized cases, phototherapy, systemic corticosteroids, acitretin, isotretinoin, or cyclosporine can be considered.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
Chu J and Lam JM. CMAJ. 2014 Dec 9;186(18):E688.
Lestringant G et al. Dermatology 1996;192:171-3.
Peterson JA et al. Proc (Bayl Univ Med Cent). 2021 Aug 25;35(1):70-2.
Schwartz C and Goodman MB. “Lichen nitidus,” in StatPearls. Treasure Island, Fla.: StatPearls Publishing, 2022.
The patient was diagnosed with lichen nitidus, given the characteristic clinical presentation.
Lichen nitidus is a rare chronic inflammatory condition of the skin that most commonly presents in children and young adults and does not seem to be restricted to any sex or race. The classic lesions are described as asymptomatic to slightly pruritic, small (1 mm), skin-colored to hypopigmented flat-topped papules.
Koebner phenomenon is usually seen in which the skin lesions appear in areas of traumatized healthy skin. The extremities, abdomen, chest, and penis are common locations for the lesions to occur. Rarely, the oral mucosa or nails can be involved. It has been described in patients with a diagnosis of Crohn’s disease, Niemann-Pick disease, Down syndrome, and HIV. The rare, generalized purpuric variant has been reported in a few cases associated with interferon and ribavirin treatment for hepatitis C infection and nivolumab treatment for cancer. The pathophysiology of lichen nitidus is unknown.
Lichen nitidus can occur in the presence of other skin conditions like lichen planus, atopic dermatitis, vitiligo, erythema nodosum, and lichen spinulosus. Histopathologic characteristics of lichen nitidus are described as a “ball and claw” of epidermal rete around a lymphohistiocytic infiltrate. Parakeratosis overlying epidermal atrophy and focal basal liquefaction degeneration is also seen.
The differential diagnosis of lichen nitidus includes flat warts, which can present as clusters of small flat-topped papules that can show a pseudo-Koebner phenomenon (where the virus is seeded in traumatized skin). The morphological difference between the condition is that lichen nitidus lesions are usually monomorphic, compared with flat warts, which usually present with different sizes and shapes.
Patients with a history of allergic contact dermatitis may present with a generalized monomorphic eruption of skin-colored papules (known as ID reaction) that can sometimes be very similar to lichen nitidus. Allergic contact dermatitis tends to respond fairly quickly to topical or systemic corticosteroids, unlike lichen nitidus. There are a few reports that consider lichen nitidus to be a variant of lichen planus, although they have different histopathologic findings. Lichen planus lesions are described as polygonal, pruritic, purple to pink papules most commonly seen on the wrists, lower back, and ankles. Lichen planus can be seen in patients with hepatitis C and may also occur secondary to medication.
Milia are small keratin cysts on the skin that are commonly seen in babies as primary milia and can be seen in older children secondary to trauma (commonly on the eyelids) or medications. Given their size and monomorphic appearance, they can sometimes be confused with lichen nitidus.
Lichen nitidus is often asymptomatic and the lesions resolve within a few months to years. Topical corticosteroids can be helpful to alleviate the symptoms in patients who present with pruritus. In more persistent and generalized cases, phototherapy, systemic corticosteroids, acitretin, isotretinoin, or cyclosporine can be considered.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
Chu J and Lam JM. CMAJ. 2014 Dec 9;186(18):E688.
Lestringant G et al. Dermatology 1996;192:171-3.
Peterson JA et al. Proc (Bayl Univ Med Cent). 2021 Aug 25;35(1):70-2.
Schwartz C and Goodman MB. “Lichen nitidus,” in StatPearls. Treasure Island, Fla.: StatPearls Publishing, 2022.
An 11-year-old male with a prior history of atopic dermatitis as a young child, presents with 6 months of slightly itchy, small bumps on the wrists, face, arms, and legs. Has been treated with fluocinolone oil and hydrocortisone 2.5% for a month with no change in the lesions. Besides the use of topical corticosteroids, he has not been taking any other medications.
On physical examination he has multiple skin-colored, flat-topped papules that coalesce into plaques on the arms, legs, chest, and back (Photo 1). Koebner phenomenon was also seen on the knees and arms. There were no lesions in the mouth or on the nails.
Embattled iPLEDGE program: Changes ahead?
In December 2021, major changes took effect in the iPLEDGE program, the Food and Drug Administration–required safety program for managing the risks of isotretinoin’s teratogenicity and preventing exposure during pregnancy. Now, more modifications may be coming to the acne drug’s safety program.
The risk evaluation and mitigation strategy (REMS) requirements. The aim, according to the FDA meeting announcement, is “to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.”
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane. Its former brand name was Accutane.
Problems began to surface days after a new, gender-neutral approach to the risk mitigation program was launched on Dec. 13, 2021. That program had been approved earlier by the FDA.
However, the problems that were encountered were a result of glitches in changes in the platform that had been planned, and were not related to the gender-neutral changes. The iPLEDGE program had transitioned to the new platform, and the rollout was far from smooth. Dermatologists, pharmacists, patients, parents of patients, and others were frustrated and angry that they could not access the new platform and obtain the medication promptly. Reaching the help line to sort out problems was another exercise in frustration. Wait times while on hold were unbearably long, or problems were not resolved over the phone.
(The new gender-neutral approach, which advocates said was needed to preserve inclusiveness of their patients, including transgender patients, places potential patients into two categories: those who can become pregnant, and those who cannot. Previously, there were three categories into which patients were classified: females who have reproductive potential, females who do not have reproductive potential, and males.)
Before pharmacists can fill a prescription for isotretinoin, a medical provider must confirm a patient’s negative pregnancy test and inform a patient with reproductive potential of the risks of the medication.
In January 2022, to deal with the chaotic launch and subsequent problems, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve the problems reported by clinicians, pharmacists, and patients.
The American Academy of Dermatology Association formed an iPLEDGE work group to address the issues and suggest solutions. It has made several requests of and suggestions for the IPMG, which manages the program, according to Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at Penn State Hershey (Pa.) Medical Center, and a member of the work group.
“We are asking them to eliminate the monthly attestation for patients who can’t get pregnant and to review and modify restrictive and punitive waiting and lockout periods for all patients,” she told this news organization.
As of February 2023, most of the platform glitches had been smoothed out, Dr. Zaenglein said. Still, “improvements to the design of the website could improve the user interface,” she added.
The FDA has established a docket for the public to submit comments before the meeting. The docket number is FDA-2022-N-3071. The electronic filing system will accept comments until 11:59 p.m. Eastern time on March 27. Background material and a link to the live webcast of the panel meeting will be available to the public no later than 2 days before the meeting and will be posted on the FDA web page or at the time of the meeting.
A version of this article first appeared on Medscape.com.
In December 2021, major changes took effect in the iPLEDGE program, the Food and Drug Administration–required safety program for managing the risks of isotretinoin’s teratogenicity and preventing exposure during pregnancy. Now, more modifications may be coming to the acne drug’s safety program.
The risk evaluation and mitigation strategy (REMS) requirements. The aim, according to the FDA meeting announcement, is “to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.”
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane. Its former brand name was Accutane.
Problems began to surface days after a new, gender-neutral approach to the risk mitigation program was launched on Dec. 13, 2021. That program had been approved earlier by the FDA.
However, the problems that were encountered were a result of glitches in changes in the platform that had been planned, and were not related to the gender-neutral changes. The iPLEDGE program had transitioned to the new platform, and the rollout was far from smooth. Dermatologists, pharmacists, patients, parents of patients, and others were frustrated and angry that they could not access the new platform and obtain the medication promptly. Reaching the help line to sort out problems was another exercise in frustration. Wait times while on hold were unbearably long, or problems were not resolved over the phone.
(The new gender-neutral approach, which advocates said was needed to preserve inclusiveness of their patients, including transgender patients, places potential patients into two categories: those who can become pregnant, and those who cannot. Previously, there were three categories into which patients were classified: females who have reproductive potential, females who do not have reproductive potential, and males.)
Before pharmacists can fill a prescription for isotretinoin, a medical provider must confirm a patient’s negative pregnancy test and inform a patient with reproductive potential of the risks of the medication.
In January 2022, to deal with the chaotic launch and subsequent problems, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve the problems reported by clinicians, pharmacists, and patients.
The American Academy of Dermatology Association formed an iPLEDGE work group to address the issues and suggest solutions. It has made several requests of and suggestions for the IPMG, which manages the program, according to Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at Penn State Hershey (Pa.) Medical Center, and a member of the work group.
“We are asking them to eliminate the monthly attestation for patients who can’t get pregnant and to review and modify restrictive and punitive waiting and lockout periods for all patients,” she told this news organization.
As of February 2023, most of the platform glitches had been smoothed out, Dr. Zaenglein said. Still, “improvements to the design of the website could improve the user interface,” she added.
The FDA has established a docket for the public to submit comments before the meeting. The docket number is FDA-2022-N-3071. The electronic filing system will accept comments until 11:59 p.m. Eastern time on March 27. Background material and a link to the live webcast of the panel meeting will be available to the public no later than 2 days before the meeting and will be posted on the FDA web page or at the time of the meeting.
A version of this article first appeared on Medscape.com.
In December 2021, major changes took effect in the iPLEDGE program, the Food and Drug Administration–required safety program for managing the risks of isotretinoin’s teratogenicity and preventing exposure during pregnancy. Now, more modifications may be coming to the acne drug’s safety program.
The risk evaluation and mitigation strategy (REMS) requirements. The aim, according to the FDA meeting announcement, is “to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of isotretinoin oral capsules for patients.”
Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane. Its former brand name was Accutane.
Problems began to surface days after a new, gender-neutral approach to the risk mitigation program was launched on Dec. 13, 2021. That program had been approved earlier by the FDA.
However, the problems that were encountered were a result of glitches in changes in the platform that had been planned, and were not related to the gender-neutral changes. The iPLEDGE program had transitioned to the new platform, and the rollout was far from smooth. Dermatologists, pharmacists, patients, parents of patients, and others were frustrated and angry that they could not access the new platform and obtain the medication promptly. Reaching the help line to sort out problems was another exercise in frustration. Wait times while on hold were unbearably long, or problems were not resolved over the phone.
(The new gender-neutral approach, which advocates said was needed to preserve inclusiveness of their patients, including transgender patients, places potential patients into two categories: those who can become pregnant, and those who cannot. Previously, there were three categories into which patients were classified: females who have reproductive potential, females who do not have reproductive potential, and males.)
Before pharmacists can fill a prescription for isotretinoin, a medical provider must confirm a patient’s negative pregnancy test and inform a patient with reproductive potential of the risks of the medication.
In January 2022, to deal with the chaotic launch and subsequent problems, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve the problems reported by clinicians, pharmacists, and patients.
The American Academy of Dermatology Association formed an iPLEDGE work group to address the issues and suggest solutions. It has made several requests of and suggestions for the IPMG, which manages the program, according to Andrea L. Zaenglein, MD, professor of dermatology and pediatrics at Penn State Hershey (Pa.) Medical Center, and a member of the work group.
“We are asking them to eliminate the monthly attestation for patients who can’t get pregnant and to review and modify restrictive and punitive waiting and lockout periods for all patients,” she told this news organization.
As of February 2023, most of the platform glitches had been smoothed out, Dr. Zaenglein said. Still, “improvements to the design of the website could improve the user interface,” she added.
The FDA has established a docket for the public to submit comments before the meeting. The docket number is FDA-2022-N-3071. The electronic filing system will accept comments until 11:59 p.m. Eastern time on March 27. Background material and a link to the live webcast of the panel meeting will be available to the public no later than 2 days before the meeting and will be posted on the FDA web page or at the time of the meeting.
A version of this article first appeared on Medscape.com.
FDA expands oral JAK abrocitinib to adolescents with AD
Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.
It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.
The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.
Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.
The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.
Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.
Select JADE TEEN findings include the following:
- IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
- EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
- Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.
Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.
In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.
He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.
Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.
JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.
Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.
A version of this article first appeared on Medscape.com.
Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.
It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.
The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.
Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.
The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.
Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.
Select JADE TEEN findings include the following:
- IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
- EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
- Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.
Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.
In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.
He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.
Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.
JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.
Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.
A version of this article first appeared on Medscape.com.
Abrocitinib, taken once daily, previously was approved only for treating adults aged 18 and older.
It joins upadacitinib (Rinvoq), previously the only oral JAK inhibitor to be approved for use by adolescents aged 12 through 17 with refractory moderate to severe AD.
The indication has been expanded for teens whose disease is not adequately controlled with other systemic drugs, including biologics, or those for whom use of those drugs is not advised.
Prescribing information was updated to reflect data from JADE TEEN, a phase 3, randomized, placebo-controlled trial that supported the indication for adolescents. That trial evaluated both the 100-mg and 200-mg doses of abrocitinib in comparison with placebo in 285 adolescents aged 12-18 who had moderate to severe AD and who were also receiving background therapy with topical medications.
The most common toxicities that were reported in at least 1% of patients treated with abrocitinib for up to 16 weeks included nasopharyngitis, nausea, and headache.
Efficacy measures included improvements in itch, skin clearance, and disease severity using the Investigator Global Assessment (IGA), the Peak Pruritus Numerical Rating Scale (PP-NRS), and the Eczema Area and Severity Index (EASI), according to the Pfizer statement announcing the expanded approval.
Select JADE TEEN findings include the following:
- IGA response rate of 0 or 1 at week 12: 39% with abrocitinib 100 mg; 46% with abrocitinib 200 mg; and 24% with placebo.
- EASI-75 response rate at week 12: 64%, 71%, and 41%, respectively.
- Proportion of participants achieving PP-NRS with at least a 4-point decrease from baseline at week 2: 13%, 25%, and 8%, respectively.
Data included in the prescribing information now encompass five randomized, placebo-controlled clinical trials and a long-term extension study with more than 1,600 patients treated with abrocitinib, according to the statement from Pfizer.
In a 2021 story, when JADE TEEN trial results were presented, Lawrence Eichenfield, MD, professor of dermatology and pediatrics, University of California, San Diego, and Rady Children’s Hospital, San Diego, told this news organization that he welcomed oral JAKs as a weapon against atopic dermatitis.
He noted that moderate to severe AD can have a tremendous impact on adolescents. “Traditionally, we have treated it with intermittent topical corticosteroids, but this has left a significant percentage of patients without long-term disease control,” he said.
Abrocitinib is not recommended for use with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
AD, one of the most common inflammatory skin diseases, affects approximately 5%-10% of adults in the United States and approximately 11% of children. About one in three adults and one in three children and adolescents aged 17 and younger with AD have moderate to severe disease.
JAK inhibition is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin.
Prescribing information includes a warning that use of abrocitinib should be avoided by patients with an active, serious infection, including localized infections. A boxed warning is included in the labels of JAK inhibitors regarding the risk of serious infections, mortality, major cardiovascular events, and thrombosis.
Treatment risks and benefits should be carefully considered for patients with chronic or recurrent infections or those who have lived in or traveled in areas of endemic tuberculosis or endemic mycoses, the information states.
A version of this article first appeared on Medscape.com.
Study documents link between preadolescent acne and elevated BMI
The that used age- and sex-matched controls.
The investigators also identified “a potential association” with precocious puberty that they said “should be considered, especially among those presenting [with acne] under 8 or 9 years old.” The study was published in Pediatric Dermatology .
Senior author Megha M. Tollefson, MD, and coauthors used resources of the Rochester Epidemiology Project to identify all residents of Olmstead County, Minn., who were diagnosed with acne between the ages of 7 and 12 years during 2010-2018. They then randomly selected two age and sex-matched community controls in order to evaluate the relationship of preadolescent acne and BMI.
They confirmed 643 acne cases, and calculated an annual age- and sex-adjusted incidence rate for ages 7-12 of 58 per 10,000 person-years (95% confidence interval, 53.5-62.5). The incidence rate was significantly higher in females than males (89.2 vs. 28.2 per 10,000 person-years; P < .001), and it significantly increased with age (incidence rates of 4.3, 24.4, and 144.3 per 10,000 person-years among those ages 7-8, 9-10, and 11-12 years, respectively).
The median BMI percentile among children with acne was significantly higher than those without an acne diagnosis (75.0 vs. 65.0; P <.001). They also were much more likely to be obese: 16.7% of the children with acne had a BMI in at least the 95th percentile, compared with 12.2% among controls with no acne diagnosis (P = .01). (The qualifying 581 acne cases for this analysis had BMIs recorded within 8 months of the index data, in addition to not having pre-existing acne-relevant endocrine disorders.)
“High BMI is a strong risk factor for acne development and severity in adults, but until now pediatric studies have revealed mixed information ... [and have been] largely retrospective reviews without controls,” Dr. Tollefson, professor of pediatrics and dermatology at the Mayo Clinic, Rochester, Minn., and colleagues wrote.
‘Valuable’ data
Leah Lalor, MD, a pediatric dermatologist not involved with the research, said she is happy to see it. “It’s really valuable,” she said in an interview. “It’s actually the first study that gives us incidence data for preadolescent acne. We all have [had our estimates], but this study quantifies it ... and it will set the stage for further studies of preadolescents in the future.”
The study also documents that “girls are more likely to present to the clinic with acne, and to do so at younger ages, which we’ve suspected and which makes physiologic sense since girls tend to go through puberty earlier than boys,” said Dr. Lalor, assistant professor of dermatology and pediatrics at the Medical College of Wisconsin and the Children’s Wisconsin Clinics, both in Milwaukee. “And most interestingly, it really reveals that BMI is higher among preadolescents with acne than those without.”
The important caveat, she emphasized, is that the study population in Olmstead County, Minn. has a relatively higher level of education, wealth, and employment than the rest of the United States.
The investigators also found that use of systemic acne medications increased with increasing BMI (odds ratio, 1.43 per 5 kg/m2 increase in BMI; 95% CI, 1.07-1.92; P = .015). Approximately 5% of underweight or normal children were prescribed systemic acne medications, compared with 8.1% of overweight children, and 10.3% of those who were obese – data that suggest that most preadolescents with acne had mild to moderate disease and that more severe acne may be associated with increasing BMI percentiles, the authors wrote.
Approximately 4% of the 643 preadolescents with acne were diagnosed with an acne-relevant endocrine disorder prior to or at the time of acne diagnosis – most commonly precocious puberty. Of the 24 diagnoses of precocious puberty, 22 were in females, with a mean age at diagnosis of 7.3 years.
Puberty before age 8 in girls and 9 in boys is classified as precocious puberty. “Thus, a thorough review of systems and exam should be done in this population [with acne] to look for precocious puberty with a low threshold for systemic evaluation if indicated,” the authors wrote, also noting that 19 or the 482 female patients with acne were subsequently diagnosed with polycystic ovary syndrome.
Dr. Lalor said she “automatically” refers children with acne who are younger than 7 for an endocrine workup, but not necessarily children ages 7, 8, or 9 because “that’s considered within the normal realm of starting to get some acne.” Acne in the context of other symptoms such as body odor, hair, or thelarche may prompt referral in these ages, however, she said.
Future research
Obesity may influence preadolescent acne development through its effect on puberty, as overweight and obese girls achieve puberty earlier than those with normal BMI. And “insulin resistance, which may be related to obesity, has been implicated with inducing or worsening acne potentially related to shifts in IGF-1 [insulin-like growth factor 1] signaling and hyperandrogenemia,” Dr. Tollefson and colleagues wrote. Nutrition is also a possible confounder in the study.
“Patients and families have long felt that certain foods or practices contribute to acne, though this has been difficult to prove,” Dr. Lalor said. “We know that excess skim milk seems to contribute ... and there’s a correlation between high glycemic load diets [and acne].”
Assessing dietary habits in conjunction with BMI, and acne incidence and severity, would be valuable. So would research to determine “if decreasing the BMI percentile [in children with acne] would improve or prevent acne, without doing any acne treatments,” she said.
The study was supported by the National Institute on Aging and the Rochester Epidemiology Project. The authors reported no conflicts of interest. Dr. Lalor also reported no conflicts of interest.
The that used age- and sex-matched controls.
The investigators also identified “a potential association” with precocious puberty that they said “should be considered, especially among those presenting [with acne] under 8 or 9 years old.” The study was published in Pediatric Dermatology .
Senior author Megha M. Tollefson, MD, and coauthors used resources of the Rochester Epidemiology Project to identify all residents of Olmstead County, Minn., who were diagnosed with acne between the ages of 7 and 12 years during 2010-2018. They then randomly selected two age and sex-matched community controls in order to evaluate the relationship of preadolescent acne and BMI.
They confirmed 643 acne cases, and calculated an annual age- and sex-adjusted incidence rate for ages 7-12 of 58 per 10,000 person-years (95% confidence interval, 53.5-62.5). The incidence rate was significantly higher in females than males (89.2 vs. 28.2 per 10,000 person-years; P < .001), and it significantly increased with age (incidence rates of 4.3, 24.4, and 144.3 per 10,000 person-years among those ages 7-8, 9-10, and 11-12 years, respectively).
The median BMI percentile among children with acne was significantly higher than those without an acne diagnosis (75.0 vs. 65.0; P <.001). They also were much more likely to be obese: 16.7% of the children with acne had a BMI in at least the 95th percentile, compared with 12.2% among controls with no acne diagnosis (P = .01). (The qualifying 581 acne cases for this analysis had BMIs recorded within 8 months of the index data, in addition to not having pre-existing acne-relevant endocrine disorders.)
“High BMI is a strong risk factor for acne development and severity in adults, but until now pediatric studies have revealed mixed information ... [and have been] largely retrospective reviews without controls,” Dr. Tollefson, professor of pediatrics and dermatology at the Mayo Clinic, Rochester, Minn., and colleagues wrote.
‘Valuable’ data
Leah Lalor, MD, a pediatric dermatologist not involved with the research, said she is happy to see it. “It’s really valuable,” she said in an interview. “It’s actually the first study that gives us incidence data for preadolescent acne. We all have [had our estimates], but this study quantifies it ... and it will set the stage for further studies of preadolescents in the future.”
The study also documents that “girls are more likely to present to the clinic with acne, and to do so at younger ages, which we’ve suspected and which makes physiologic sense since girls tend to go through puberty earlier than boys,” said Dr. Lalor, assistant professor of dermatology and pediatrics at the Medical College of Wisconsin and the Children’s Wisconsin Clinics, both in Milwaukee. “And most interestingly, it really reveals that BMI is higher among preadolescents with acne than those without.”
The important caveat, she emphasized, is that the study population in Olmstead County, Minn. has a relatively higher level of education, wealth, and employment than the rest of the United States.
The investigators also found that use of systemic acne medications increased with increasing BMI (odds ratio, 1.43 per 5 kg/m2 increase in BMI; 95% CI, 1.07-1.92; P = .015). Approximately 5% of underweight or normal children were prescribed systemic acne medications, compared with 8.1% of overweight children, and 10.3% of those who were obese – data that suggest that most preadolescents with acne had mild to moderate disease and that more severe acne may be associated with increasing BMI percentiles, the authors wrote.
Approximately 4% of the 643 preadolescents with acne were diagnosed with an acne-relevant endocrine disorder prior to or at the time of acne diagnosis – most commonly precocious puberty. Of the 24 diagnoses of precocious puberty, 22 were in females, with a mean age at diagnosis of 7.3 years.
Puberty before age 8 in girls and 9 in boys is classified as precocious puberty. “Thus, a thorough review of systems and exam should be done in this population [with acne] to look for precocious puberty with a low threshold for systemic evaluation if indicated,” the authors wrote, also noting that 19 or the 482 female patients with acne were subsequently diagnosed with polycystic ovary syndrome.
Dr. Lalor said she “automatically” refers children with acne who are younger than 7 for an endocrine workup, but not necessarily children ages 7, 8, or 9 because “that’s considered within the normal realm of starting to get some acne.” Acne in the context of other symptoms such as body odor, hair, or thelarche may prompt referral in these ages, however, she said.
Future research
Obesity may influence preadolescent acne development through its effect on puberty, as overweight and obese girls achieve puberty earlier than those with normal BMI. And “insulin resistance, which may be related to obesity, has been implicated with inducing or worsening acne potentially related to shifts in IGF-1 [insulin-like growth factor 1] signaling and hyperandrogenemia,” Dr. Tollefson and colleagues wrote. Nutrition is also a possible confounder in the study.
“Patients and families have long felt that certain foods or practices contribute to acne, though this has been difficult to prove,” Dr. Lalor said. “We know that excess skim milk seems to contribute ... and there’s a correlation between high glycemic load diets [and acne].”
Assessing dietary habits in conjunction with BMI, and acne incidence and severity, would be valuable. So would research to determine “if decreasing the BMI percentile [in children with acne] would improve or prevent acne, without doing any acne treatments,” she said.
The study was supported by the National Institute on Aging and the Rochester Epidemiology Project. The authors reported no conflicts of interest. Dr. Lalor also reported no conflicts of interest.
The that used age- and sex-matched controls.
The investigators also identified “a potential association” with precocious puberty that they said “should be considered, especially among those presenting [with acne] under 8 or 9 years old.” The study was published in Pediatric Dermatology .
Senior author Megha M. Tollefson, MD, and coauthors used resources of the Rochester Epidemiology Project to identify all residents of Olmstead County, Minn., who were diagnosed with acne between the ages of 7 and 12 years during 2010-2018. They then randomly selected two age and sex-matched community controls in order to evaluate the relationship of preadolescent acne and BMI.
They confirmed 643 acne cases, and calculated an annual age- and sex-adjusted incidence rate for ages 7-12 of 58 per 10,000 person-years (95% confidence interval, 53.5-62.5). The incidence rate was significantly higher in females than males (89.2 vs. 28.2 per 10,000 person-years; P < .001), and it significantly increased with age (incidence rates of 4.3, 24.4, and 144.3 per 10,000 person-years among those ages 7-8, 9-10, and 11-12 years, respectively).
The median BMI percentile among children with acne was significantly higher than those without an acne diagnosis (75.0 vs. 65.0; P <.001). They also were much more likely to be obese: 16.7% of the children with acne had a BMI in at least the 95th percentile, compared with 12.2% among controls with no acne diagnosis (P = .01). (The qualifying 581 acne cases for this analysis had BMIs recorded within 8 months of the index data, in addition to not having pre-existing acne-relevant endocrine disorders.)
“High BMI is a strong risk factor for acne development and severity in adults, but until now pediatric studies have revealed mixed information ... [and have been] largely retrospective reviews without controls,” Dr. Tollefson, professor of pediatrics and dermatology at the Mayo Clinic, Rochester, Minn., and colleagues wrote.
‘Valuable’ data
Leah Lalor, MD, a pediatric dermatologist not involved with the research, said she is happy to see it. “It’s really valuable,” she said in an interview. “It’s actually the first study that gives us incidence data for preadolescent acne. We all have [had our estimates], but this study quantifies it ... and it will set the stage for further studies of preadolescents in the future.”
The study also documents that “girls are more likely to present to the clinic with acne, and to do so at younger ages, which we’ve suspected and which makes physiologic sense since girls tend to go through puberty earlier than boys,” said Dr. Lalor, assistant professor of dermatology and pediatrics at the Medical College of Wisconsin and the Children’s Wisconsin Clinics, both in Milwaukee. “And most interestingly, it really reveals that BMI is higher among preadolescents with acne than those without.”
The important caveat, she emphasized, is that the study population in Olmstead County, Minn. has a relatively higher level of education, wealth, and employment than the rest of the United States.
The investigators also found that use of systemic acne medications increased with increasing BMI (odds ratio, 1.43 per 5 kg/m2 increase in BMI; 95% CI, 1.07-1.92; P = .015). Approximately 5% of underweight or normal children were prescribed systemic acne medications, compared with 8.1% of overweight children, and 10.3% of those who were obese – data that suggest that most preadolescents with acne had mild to moderate disease and that more severe acne may be associated with increasing BMI percentiles, the authors wrote.
Approximately 4% of the 643 preadolescents with acne were diagnosed with an acne-relevant endocrine disorder prior to or at the time of acne diagnosis – most commonly precocious puberty. Of the 24 diagnoses of precocious puberty, 22 were in females, with a mean age at diagnosis of 7.3 years.
Puberty before age 8 in girls and 9 in boys is classified as precocious puberty. “Thus, a thorough review of systems and exam should be done in this population [with acne] to look for precocious puberty with a low threshold for systemic evaluation if indicated,” the authors wrote, also noting that 19 or the 482 female patients with acne were subsequently diagnosed with polycystic ovary syndrome.
Dr. Lalor said she “automatically” refers children with acne who are younger than 7 for an endocrine workup, but not necessarily children ages 7, 8, or 9 because “that’s considered within the normal realm of starting to get some acne.” Acne in the context of other symptoms such as body odor, hair, or thelarche may prompt referral in these ages, however, she said.
Future research
Obesity may influence preadolescent acne development through its effect on puberty, as overweight and obese girls achieve puberty earlier than those with normal BMI. And “insulin resistance, which may be related to obesity, has been implicated with inducing or worsening acne potentially related to shifts in IGF-1 [insulin-like growth factor 1] signaling and hyperandrogenemia,” Dr. Tollefson and colleagues wrote. Nutrition is also a possible confounder in the study.
“Patients and families have long felt that certain foods or practices contribute to acne, though this has been difficult to prove,” Dr. Lalor said. “We know that excess skim milk seems to contribute ... and there’s a correlation between high glycemic load diets [and acne].”
Assessing dietary habits in conjunction with BMI, and acne incidence and severity, would be valuable. So would research to determine “if decreasing the BMI percentile [in children with acne] would improve or prevent acne, without doing any acne treatments,” she said.
The study was supported by the National Institute on Aging and the Rochester Epidemiology Project. The authors reported no conflicts of interest. Dr. Lalor also reported no conflicts of interest.
FROM PEDIATRIC DERMATOLOGY