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How to Reduce Cardiovascular Morbidity and Mortality in Psoriasis and PsA
Patients with psoriatic disease have significantly higher risks of myocardial infarction, stroke, and cardiovascular mortality than does the general population, yet research consistently paints what dermatologist Joel M. Gelfand, MD, calls an “abysmal” picture: Only a minority of patients with psoriatic disease know about their increased risks, only a minority of dermatologists and rheumatologists screen for cardiovascular risk factors like lipid levels and blood pressure, and only a minority of patients diagnosed with hyperlipidemia are adequately treated with statin therapy.
In the literature and at medical meetings, Dr. Gelfand and others who have studied cardiovascular disease (CVD) comorbidity and physician practices have been urging dermatologists and rheumatologists to play a more consistent and active role in primary cardiovascular prevention for patients with psoriatic disease, who are up to 50% more likely than patients without it to develop CVD and who tend to have atherosclerosis at earlier ages.
According to the 2019 joint American Academy of Dermatology (AAD)–National Psoriasis Foundation (NPF) guidelines for managing psoriasis “with awareness and attention to comorbidities,” this means not only ensuring that all patients with psoriasis receive standard CV risk assessment (screening for hypertension, diabetes, and hyperlipidemia), but also recognizing that patients who are candidates for systemic therapy or phototherapy — or who have psoriasis involving > 10% of body surface area — may benefit from earlier and more frequent screening.
CV risk and premature mortality rises with the severity of skin disease, and patients with psoriatic arthritis (PsA) are believed to have risk levels similar to patients with moderate-severe psoriasis, cardiologist Michael S. Garshick, MD, director of the cardio-rheumatology program at New York University Langone Health, said in an interview.
In a recent survey study of 100 patients seen at NYU Langone Health’s psoriasis specialty clinic, only one-third indicated they had been advised by their physicians to be screened for CV risk factors, and only one-third reported having been told of the connection between psoriasis and CVD risk. Dr. Garshick shared the unpublished findings at the annual research symposium of the NPF in October.
Similarly, data from the National Ambulatory Medical Care Survey shows that just 16% of psoriasis-related visits to dermatology providers from 2007 to 2016 involved screening for CV risk factors. Screening rates were 11% for body mass index, 7.4% for blood pressure, 2.9% for cholesterol, and 1.7% for glucose, Dr. Gelfand and coauthors reported in 2023. .
Such findings are concerning because research shows that fewer than a quarter of patients with psoriasis have a primary care visit within a year of establishing care with their physicians, and that, overall, fewer than half of commercially insured adults under age 65 visit a primary care physician each year, according to John S. Barbieri, MD, of the department of dermatology at Brigham and Women’s Hospital in Boston. He included these findings when reporting in 2022 on a survey study on CVD screening.
In many cases, dermatologists and rheumatologists may be the primary providers for patients with psoriatic disease. So, “the question is, how can the dermatologist or rheumatologist use their interactions as a touchpoint to improve the patient’s well-being?” Dr. Barbieri said in an interview.
For the dermatologist, educating patients about the higher CVD risk fits well into conversations about “how there may be inflammation inside the body as well as in the skin,” he said. “Talk about cardiovascular risk just as you talk about PsA risk.” Both specialists, he added, can incorporate blood pressure readings and look for opportunities to measure lipid levels and hemoglobin A1c (HbA1c). These labs can easily be integrated into a biologic work-up.
“The hard part — and this needs to be individualized — is how do you want to handle [abnormal readings]? Do you want to take on a lot of the ownership and calculate [10-year CVD] risk scores and then counsel patients accordingly?” Dr. Barbieri said. “Or do you want to try to refer, and encourage them to work with their PCP? There a high-touch version and a low-touch version of how you can turn screening into action, into a care plan.”
Beyond traditional risk elevation, the primary care hand-off
Rheumatologists “in general may be more apt to screen for cardiovascular disease” as a result of their internal medicine residency training, and “we’re generally more comfortable prescribing ... if we need to,” said Alexis R. Ogdie, MD, a rheumatologist at the Hospital of the University of Pennsylvania, Philadelphia, and director of the Penn Psoriatic Arthritis Clinic.
Referral to a preventive cardiologist for management of abnormal lab results or ongoing monitoring and prevention is ideal, but when hand-offs to primary care physicians are made — the more common scenario — education is important. “A common problem is that there is underrecognition of the cardiovascular risk being elevated in our patients,” she said, above and beyond risk posed by traditional risk factors such as dyslipidemia, hypertension, metabolic syndrome, and obesity, all of which have been shown to occur more frequently in patients with psoriatic disease than in the general population.
Risk stratification guides CVD prevention in the general population, and “if you use typical scores for cardiovascular risk, they may underestimate risk for our patients with PsA,” said Dr. Ogdie, who has reported on CV risk in patients with PsA. “Relative to what the patient’s perceived risk is, they may be treated similarly (to the general population). But relative to their actual risk, they’re undertreated.”
The 2019 AAD-NPF psoriasis guidelines recommend utilizing a 1.5 multiplication factor in risk score models, such as the American College of Cardiology’s Atherosclerotic Cardiovascular Disease (ASCVD) Risk Estimator, when the patient has a body surface area >10% or is a candidate for systemic therapy or phototherapy.
Similarly, the 2018 American Heart Association (AHA)-ACC Guideline on the Management of Blood Cholesterol defines psoriasis, along with RA, metabolic syndrome, HIV, and other diseases, as a “cardiovascular risk enhancer” that should be factored into assessments of ASCVD risk. (The guideline does not specify a psoriasis severity threshold.)
“It’s the first time the specialty [of cardiology] has said, ‘pay attention to a skin disease,’ ” Dr. Gelfand said at the NPF meeting.
Using the 1.5 multiplication factor, a patient who otherwise would be classified in the AHA/ACC guideline as “borderline risk,” with a 10-year ASCVD risk of 5% to <7.5%, would instead have an “intermediate” 10-year ASCVD risk of ≥7.5% to <20%. Application of the AHA-ACC “risk enhancer” would have a similar effect.
For management, the main impact of psoriasis being considered a risk enhancer is that “it lowers the threshold for treatment with standard cardiovascular prevention medications such as statins.”
In general, “we should be taking a more aggressive approach to the management of traditional cardiovascular risk factors” in patients with psoriatic disease, he said. Instead of telling a patient with mildly elevated blood pressure, ‘I’ll see you in a year or two,’ or a patient entering a prediabetic stage to “watch what you eat, and I’ll see you in a couple of years,” clinicians need to be more vigilant.
“It’s about recognizing that these traditional cardiometabolic risk factors, synergistically with psoriasis, can start enhancing CV risk at an earlier age than we might expect,” said Dr. Garshick, whose 2021 review of CV risk in psoriasis describes how the inflammatory milieu in psoriasis is linked to atherosclerosis development.
Cardiologists are aware of this, but “many primary care physicians are not. It takes time for medical knowledge to diffuse,” Dr. Gelfand said. “Tell the PCP, in notes or in a form letter, that there is a higher risk of CV disease, and reference the AHA/ACC guidelines,” he advised. “You don’t want your patient to go to their doctor and the doctor to [be uninformed].”
‘Patients trust us’
Dr. Gelfand has been at the forefront of research on psoriasis and heart disease. A study he coauthored in 2006, for instance, documented an independent risk of MI, with adjusted relative risks of 1.29 and 3.10 for a 30-year-old patient with mild or severe disease, respectively, and higher risks for a 60-year-old. In 2010, he and coinvestigators found that severe psoriasis was an independent risk factor for CV mortality (HR, 1.57) after adjusting for age, sex, smoking, diabetes, hypertension, and hyperlipidemia.
Today, along with Dr. Barbieri, Dr. Ogdie, and others, he is studying the feasibility and efficacy of a proposed national, “centralized care coordinator” model of care whereby dermatologists and rheumatologists would educate the patient, order lipid and HbA1c measurements as medically appropriate, and then refer patients as needed to a care coordinator. The care coordinator would calculate a 10-year CVD risk score and counsel the patient on possible next steps.
In a pilot study of 85 patients at four sites, 92% of patients followed through on their physician’s recommendations to have labs drawn, and 86% indicated the model was acceptable and feasible. A total of 27% of patients had “newly identified, previously undiagnosed, elevated cardiovascular disease risk,” and exploratory effectiveness results indicated a successful reduction in predicted CVD risk in patients who started statins, Dr. Gelfand reported at the NPF meeting.
With funding from the NPF, a larger, single-arm, pragmatic “CP3” trial (NCT05908240) is enrolling 525 patients with psoriasis at 10-20 academic and nonacademic dermatology sites across the United States to further test the model. The primary endpoint will be the change in LDL cholesterol measured at 6 months among people with a 10-year risk ≥5%. Secondary endpoints will cover improvement in disease severity and quality of life, behavior modification, patient experience, and other issues.
“We have only 10-15 minutes [with patients] ... a care coordinator who is empathetic and understanding and [informed] could make a big difference,” Dr. Gelfand said at the NPF meeting. If findings are positive, the model would be tested in rheumatology sites as well. The hope, he said, is that the NPF would be able to fund an in-house care coordinator(s) for the long-term.
Notably, a patient survey conducted as part of exploratory research leading up to the care coordinator project showed that patients trust their dermatologist or rheumatologist for CVD education and screening. Among 160 patients with psoriasis and 162 patients with PsA, 76% and 90% agreed that “I would like it if my dermatologist/rheumatologist educated me about my risk of heart disease,” and 60% and 75%, respectively, agree that “it would be convenient for me to have my cholesterol checked by my dermatologist/rheumatologist.”
“Patients trust us,” Dr. Gelfand said at the NPF meeting. “And the pilot study shows us that patients are motivated.”
Taking an individualized, holistic, longitudinal approach
“Sometimes you do have to triage bit,” Dr. Gelfand said in an interview. “For a young person with normal body weight who doesn’t smoke and has mild psoriasis, one could just educate and advise that they see their primary care physician” for monitoring.
“But for the same patient who is obese, maybe smokes, and doesn’t have a primary care physician, I’d order labs,” he said. “You don’t want a patient walking out the door with an [undiagnosed] LDL of 160 or hypertension.”
Age is also an important consideration, as excess CVD risk associated with autoimmune diseases like psoriasis rises with age, Dr. Gelfand said during a seminar on psoriasis and PsA held at NYU Langone in December. For a young person, typically, “I need to focus on education and lifestyle … setting them on a healthy lifestyle trajectory,” he said. “Once they get to 40, from 40 to 75 or so, that’s a sweet spot for medical intervention to lower cardiovascular risk.”
Even at older ages, however, lipid management is not the be-all and end-all, he said in the interview. “We have to be holistic.”
One advantage of having highly successful therapies for psoriasis, and to a lesser extent PsA, is the time that becomes available during follow-up visits — once disease is under control — to “focus on other things,” he said. Waiting until disease is under control to discuss diet, exercise, or smoking, for instance, makes sense anyway, he said. “You don’t want to overwhelm patients with too much to do at once.”
Indeed, said dermatologist Robert E. Kalb, MD, of the Buffalo Medical Group in Buffalo, NY, “patients have an open mind [about discussing cardiovascular disease risk], but it is not high on their radar. Most of them just want to get their skin clear.” (Dr. Kalb participated in the care coordinator pilot study, and said in an interview that since its completion, he has been more routinely ordering relevant labs.)
Rheumatologists are less fortunate with highly successful therapies, but “over the continuum of care, we do have time in office visits” to discuss issues like smoking, exercise, and lifestyle, Dr. Ogdie said. “I think of each of those pieces as part of our job.”
In the future, as researchers learn more about the impact of psoriasis and PsA treatments on CVD risk, it may be possible to tailor treatments or to prescribe treatments knowing that the therapies could reduce risk. Observational and epidemiologic data suggest that tumor necrosis factor-alpha inhibitor therapy over 3 years reduces the risk of MI, and that patients whose psoriasis is treated have reduced aortic inflammation, improved myocardial strain, and reduced coronary plaque burden, Dr. Garshick said at the NPF meeting.
“But when we look at the randomized controlled trials, they’re actually inconclusive that targeting inflammation in psoriatic disease reduces surrogates of cardiovascular disease,” he said. Dr. Garshick’s own research focuses on platelet and endothelial biology in psoriasis.
Dr. Barbieri reported he had no relevant disclosures. Dr. Garshick reported consulting fees from Bristol-Myers Squibb, Kiniksa, Horizon Therapeutics, and Agepha. Dr. Ogdie reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Takeda, and UCB. Dr. Gelfand reported serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, GlaxoSmithKline, and other companies.
Patients with psoriatic disease have significantly higher risks of myocardial infarction, stroke, and cardiovascular mortality than does the general population, yet research consistently paints what dermatologist Joel M. Gelfand, MD, calls an “abysmal” picture: Only a minority of patients with psoriatic disease know about their increased risks, only a minority of dermatologists and rheumatologists screen for cardiovascular risk factors like lipid levels and blood pressure, and only a minority of patients diagnosed with hyperlipidemia are adequately treated with statin therapy.
In the literature and at medical meetings, Dr. Gelfand and others who have studied cardiovascular disease (CVD) comorbidity and physician practices have been urging dermatologists and rheumatologists to play a more consistent and active role in primary cardiovascular prevention for patients with psoriatic disease, who are up to 50% more likely than patients without it to develop CVD and who tend to have atherosclerosis at earlier ages.
According to the 2019 joint American Academy of Dermatology (AAD)–National Psoriasis Foundation (NPF) guidelines for managing psoriasis “with awareness and attention to comorbidities,” this means not only ensuring that all patients with psoriasis receive standard CV risk assessment (screening for hypertension, diabetes, and hyperlipidemia), but also recognizing that patients who are candidates for systemic therapy or phototherapy — or who have psoriasis involving > 10% of body surface area — may benefit from earlier and more frequent screening.
CV risk and premature mortality rises with the severity of skin disease, and patients with psoriatic arthritis (PsA) are believed to have risk levels similar to patients with moderate-severe psoriasis, cardiologist Michael S. Garshick, MD, director of the cardio-rheumatology program at New York University Langone Health, said in an interview.
In a recent survey study of 100 patients seen at NYU Langone Health’s psoriasis specialty clinic, only one-third indicated they had been advised by their physicians to be screened for CV risk factors, and only one-third reported having been told of the connection between psoriasis and CVD risk. Dr. Garshick shared the unpublished findings at the annual research symposium of the NPF in October.
Similarly, data from the National Ambulatory Medical Care Survey shows that just 16% of psoriasis-related visits to dermatology providers from 2007 to 2016 involved screening for CV risk factors. Screening rates were 11% for body mass index, 7.4% for blood pressure, 2.9% for cholesterol, and 1.7% for glucose, Dr. Gelfand and coauthors reported in 2023. .
Such findings are concerning because research shows that fewer than a quarter of patients with psoriasis have a primary care visit within a year of establishing care with their physicians, and that, overall, fewer than half of commercially insured adults under age 65 visit a primary care physician each year, according to John S. Barbieri, MD, of the department of dermatology at Brigham and Women’s Hospital in Boston. He included these findings when reporting in 2022 on a survey study on CVD screening.
In many cases, dermatologists and rheumatologists may be the primary providers for patients with psoriatic disease. So, “the question is, how can the dermatologist or rheumatologist use their interactions as a touchpoint to improve the patient’s well-being?” Dr. Barbieri said in an interview.
For the dermatologist, educating patients about the higher CVD risk fits well into conversations about “how there may be inflammation inside the body as well as in the skin,” he said. “Talk about cardiovascular risk just as you talk about PsA risk.” Both specialists, he added, can incorporate blood pressure readings and look for opportunities to measure lipid levels and hemoglobin A1c (HbA1c). These labs can easily be integrated into a biologic work-up.
“The hard part — and this needs to be individualized — is how do you want to handle [abnormal readings]? Do you want to take on a lot of the ownership and calculate [10-year CVD] risk scores and then counsel patients accordingly?” Dr. Barbieri said. “Or do you want to try to refer, and encourage them to work with their PCP? There a high-touch version and a low-touch version of how you can turn screening into action, into a care plan.”
Beyond traditional risk elevation, the primary care hand-off
Rheumatologists “in general may be more apt to screen for cardiovascular disease” as a result of their internal medicine residency training, and “we’re generally more comfortable prescribing ... if we need to,” said Alexis R. Ogdie, MD, a rheumatologist at the Hospital of the University of Pennsylvania, Philadelphia, and director of the Penn Psoriatic Arthritis Clinic.
Referral to a preventive cardiologist for management of abnormal lab results or ongoing monitoring and prevention is ideal, but when hand-offs to primary care physicians are made — the more common scenario — education is important. “A common problem is that there is underrecognition of the cardiovascular risk being elevated in our patients,” she said, above and beyond risk posed by traditional risk factors such as dyslipidemia, hypertension, metabolic syndrome, and obesity, all of which have been shown to occur more frequently in patients with psoriatic disease than in the general population.
Risk stratification guides CVD prevention in the general population, and “if you use typical scores for cardiovascular risk, they may underestimate risk for our patients with PsA,” said Dr. Ogdie, who has reported on CV risk in patients with PsA. “Relative to what the patient’s perceived risk is, they may be treated similarly (to the general population). But relative to their actual risk, they’re undertreated.”
The 2019 AAD-NPF psoriasis guidelines recommend utilizing a 1.5 multiplication factor in risk score models, such as the American College of Cardiology’s Atherosclerotic Cardiovascular Disease (ASCVD) Risk Estimator, when the patient has a body surface area >10% or is a candidate for systemic therapy or phototherapy.
Similarly, the 2018 American Heart Association (AHA)-ACC Guideline on the Management of Blood Cholesterol defines psoriasis, along with RA, metabolic syndrome, HIV, and other diseases, as a “cardiovascular risk enhancer” that should be factored into assessments of ASCVD risk. (The guideline does not specify a psoriasis severity threshold.)
“It’s the first time the specialty [of cardiology] has said, ‘pay attention to a skin disease,’ ” Dr. Gelfand said at the NPF meeting.
Using the 1.5 multiplication factor, a patient who otherwise would be classified in the AHA/ACC guideline as “borderline risk,” with a 10-year ASCVD risk of 5% to <7.5%, would instead have an “intermediate” 10-year ASCVD risk of ≥7.5% to <20%. Application of the AHA-ACC “risk enhancer” would have a similar effect.
For management, the main impact of psoriasis being considered a risk enhancer is that “it lowers the threshold for treatment with standard cardiovascular prevention medications such as statins.”
In general, “we should be taking a more aggressive approach to the management of traditional cardiovascular risk factors” in patients with psoriatic disease, he said. Instead of telling a patient with mildly elevated blood pressure, ‘I’ll see you in a year or two,’ or a patient entering a prediabetic stage to “watch what you eat, and I’ll see you in a couple of years,” clinicians need to be more vigilant.
“It’s about recognizing that these traditional cardiometabolic risk factors, synergistically with psoriasis, can start enhancing CV risk at an earlier age than we might expect,” said Dr. Garshick, whose 2021 review of CV risk in psoriasis describes how the inflammatory milieu in psoriasis is linked to atherosclerosis development.
Cardiologists are aware of this, but “many primary care physicians are not. It takes time for medical knowledge to diffuse,” Dr. Gelfand said. “Tell the PCP, in notes or in a form letter, that there is a higher risk of CV disease, and reference the AHA/ACC guidelines,” he advised. “You don’t want your patient to go to their doctor and the doctor to [be uninformed].”
‘Patients trust us’
Dr. Gelfand has been at the forefront of research on psoriasis and heart disease. A study he coauthored in 2006, for instance, documented an independent risk of MI, with adjusted relative risks of 1.29 and 3.10 for a 30-year-old patient with mild or severe disease, respectively, and higher risks for a 60-year-old. In 2010, he and coinvestigators found that severe psoriasis was an independent risk factor for CV mortality (HR, 1.57) after adjusting for age, sex, smoking, diabetes, hypertension, and hyperlipidemia.
Today, along with Dr. Barbieri, Dr. Ogdie, and others, he is studying the feasibility and efficacy of a proposed national, “centralized care coordinator” model of care whereby dermatologists and rheumatologists would educate the patient, order lipid and HbA1c measurements as medically appropriate, and then refer patients as needed to a care coordinator. The care coordinator would calculate a 10-year CVD risk score and counsel the patient on possible next steps.
In a pilot study of 85 patients at four sites, 92% of patients followed through on their physician’s recommendations to have labs drawn, and 86% indicated the model was acceptable and feasible. A total of 27% of patients had “newly identified, previously undiagnosed, elevated cardiovascular disease risk,” and exploratory effectiveness results indicated a successful reduction in predicted CVD risk in patients who started statins, Dr. Gelfand reported at the NPF meeting.
With funding from the NPF, a larger, single-arm, pragmatic “CP3” trial (NCT05908240) is enrolling 525 patients with psoriasis at 10-20 academic and nonacademic dermatology sites across the United States to further test the model. The primary endpoint will be the change in LDL cholesterol measured at 6 months among people with a 10-year risk ≥5%. Secondary endpoints will cover improvement in disease severity and quality of life, behavior modification, patient experience, and other issues.
“We have only 10-15 minutes [with patients] ... a care coordinator who is empathetic and understanding and [informed] could make a big difference,” Dr. Gelfand said at the NPF meeting. If findings are positive, the model would be tested in rheumatology sites as well. The hope, he said, is that the NPF would be able to fund an in-house care coordinator(s) for the long-term.
Notably, a patient survey conducted as part of exploratory research leading up to the care coordinator project showed that patients trust their dermatologist or rheumatologist for CVD education and screening. Among 160 patients with psoriasis and 162 patients with PsA, 76% and 90% agreed that “I would like it if my dermatologist/rheumatologist educated me about my risk of heart disease,” and 60% and 75%, respectively, agree that “it would be convenient for me to have my cholesterol checked by my dermatologist/rheumatologist.”
“Patients trust us,” Dr. Gelfand said at the NPF meeting. “And the pilot study shows us that patients are motivated.”
Taking an individualized, holistic, longitudinal approach
“Sometimes you do have to triage bit,” Dr. Gelfand said in an interview. “For a young person with normal body weight who doesn’t smoke and has mild psoriasis, one could just educate and advise that they see their primary care physician” for monitoring.
“But for the same patient who is obese, maybe smokes, and doesn’t have a primary care physician, I’d order labs,” he said. “You don’t want a patient walking out the door with an [undiagnosed] LDL of 160 or hypertension.”
Age is also an important consideration, as excess CVD risk associated with autoimmune diseases like psoriasis rises with age, Dr. Gelfand said during a seminar on psoriasis and PsA held at NYU Langone in December. For a young person, typically, “I need to focus on education and lifestyle … setting them on a healthy lifestyle trajectory,” he said. “Once they get to 40, from 40 to 75 or so, that’s a sweet spot for medical intervention to lower cardiovascular risk.”
Even at older ages, however, lipid management is not the be-all and end-all, he said in the interview. “We have to be holistic.”
One advantage of having highly successful therapies for psoriasis, and to a lesser extent PsA, is the time that becomes available during follow-up visits — once disease is under control — to “focus on other things,” he said. Waiting until disease is under control to discuss diet, exercise, or smoking, for instance, makes sense anyway, he said. “You don’t want to overwhelm patients with too much to do at once.”
Indeed, said dermatologist Robert E. Kalb, MD, of the Buffalo Medical Group in Buffalo, NY, “patients have an open mind [about discussing cardiovascular disease risk], but it is not high on their radar. Most of them just want to get their skin clear.” (Dr. Kalb participated in the care coordinator pilot study, and said in an interview that since its completion, he has been more routinely ordering relevant labs.)
Rheumatologists are less fortunate with highly successful therapies, but “over the continuum of care, we do have time in office visits” to discuss issues like smoking, exercise, and lifestyle, Dr. Ogdie said. “I think of each of those pieces as part of our job.”
In the future, as researchers learn more about the impact of psoriasis and PsA treatments on CVD risk, it may be possible to tailor treatments or to prescribe treatments knowing that the therapies could reduce risk. Observational and epidemiologic data suggest that tumor necrosis factor-alpha inhibitor therapy over 3 years reduces the risk of MI, and that patients whose psoriasis is treated have reduced aortic inflammation, improved myocardial strain, and reduced coronary plaque burden, Dr. Garshick said at the NPF meeting.
“But when we look at the randomized controlled trials, they’re actually inconclusive that targeting inflammation in psoriatic disease reduces surrogates of cardiovascular disease,” he said. Dr. Garshick’s own research focuses on platelet and endothelial biology in psoriasis.
Dr. Barbieri reported he had no relevant disclosures. Dr. Garshick reported consulting fees from Bristol-Myers Squibb, Kiniksa, Horizon Therapeutics, and Agepha. Dr. Ogdie reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Takeda, and UCB. Dr. Gelfand reported serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, GlaxoSmithKline, and other companies.
Patients with psoriatic disease have significantly higher risks of myocardial infarction, stroke, and cardiovascular mortality than does the general population, yet research consistently paints what dermatologist Joel M. Gelfand, MD, calls an “abysmal” picture: Only a minority of patients with psoriatic disease know about their increased risks, only a minority of dermatologists and rheumatologists screen for cardiovascular risk factors like lipid levels and blood pressure, and only a minority of patients diagnosed with hyperlipidemia are adequately treated with statin therapy.
In the literature and at medical meetings, Dr. Gelfand and others who have studied cardiovascular disease (CVD) comorbidity and physician practices have been urging dermatologists and rheumatologists to play a more consistent and active role in primary cardiovascular prevention for patients with psoriatic disease, who are up to 50% more likely than patients without it to develop CVD and who tend to have atherosclerosis at earlier ages.
According to the 2019 joint American Academy of Dermatology (AAD)–National Psoriasis Foundation (NPF) guidelines for managing psoriasis “with awareness and attention to comorbidities,” this means not only ensuring that all patients with psoriasis receive standard CV risk assessment (screening for hypertension, diabetes, and hyperlipidemia), but also recognizing that patients who are candidates for systemic therapy or phototherapy — or who have psoriasis involving > 10% of body surface area — may benefit from earlier and more frequent screening.
CV risk and premature mortality rises with the severity of skin disease, and patients with psoriatic arthritis (PsA) are believed to have risk levels similar to patients with moderate-severe psoriasis, cardiologist Michael S. Garshick, MD, director of the cardio-rheumatology program at New York University Langone Health, said in an interview.
In a recent survey study of 100 patients seen at NYU Langone Health’s psoriasis specialty clinic, only one-third indicated they had been advised by their physicians to be screened for CV risk factors, and only one-third reported having been told of the connection between psoriasis and CVD risk. Dr. Garshick shared the unpublished findings at the annual research symposium of the NPF in October.
Similarly, data from the National Ambulatory Medical Care Survey shows that just 16% of psoriasis-related visits to dermatology providers from 2007 to 2016 involved screening for CV risk factors. Screening rates were 11% for body mass index, 7.4% for blood pressure, 2.9% for cholesterol, and 1.7% for glucose, Dr. Gelfand and coauthors reported in 2023. .
Such findings are concerning because research shows that fewer than a quarter of patients with psoriasis have a primary care visit within a year of establishing care with their physicians, and that, overall, fewer than half of commercially insured adults under age 65 visit a primary care physician each year, according to John S. Barbieri, MD, of the department of dermatology at Brigham and Women’s Hospital in Boston. He included these findings when reporting in 2022 on a survey study on CVD screening.
In many cases, dermatologists and rheumatologists may be the primary providers for patients with psoriatic disease. So, “the question is, how can the dermatologist or rheumatologist use their interactions as a touchpoint to improve the patient’s well-being?” Dr. Barbieri said in an interview.
For the dermatologist, educating patients about the higher CVD risk fits well into conversations about “how there may be inflammation inside the body as well as in the skin,” he said. “Talk about cardiovascular risk just as you talk about PsA risk.” Both specialists, he added, can incorporate blood pressure readings and look for opportunities to measure lipid levels and hemoglobin A1c (HbA1c). These labs can easily be integrated into a biologic work-up.
“The hard part — and this needs to be individualized — is how do you want to handle [abnormal readings]? Do you want to take on a lot of the ownership and calculate [10-year CVD] risk scores and then counsel patients accordingly?” Dr. Barbieri said. “Or do you want to try to refer, and encourage them to work with their PCP? There a high-touch version and a low-touch version of how you can turn screening into action, into a care plan.”
Beyond traditional risk elevation, the primary care hand-off
Rheumatologists “in general may be more apt to screen for cardiovascular disease” as a result of their internal medicine residency training, and “we’re generally more comfortable prescribing ... if we need to,” said Alexis R. Ogdie, MD, a rheumatologist at the Hospital of the University of Pennsylvania, Philadelphia, and director of the Penn Psoriatic Arthritis Clinic.
Referral to a preventive cardiologist for management of abnormal lab results or ongoing monitoring and prevention is ideal, but when hand-offs to primary care physicians are made — the more common scenario — education is important. “A common problem is that there is underrecognition of the cardiovascular risk being elevated in our patients,” she said, above and beyond risk posed by traditional risk factors such as dyslipidemia, hypertension, metabolic syndrome, and obesity, all of which have been shown to occur more frequently in patients with psoriatic disease than in the general population.
Risk stratification guides CVD prevention in the general population, and “if you use typical scores for cardiovascular risk, they may underestimate risk for our patients with PsA,” said Dr. Ogdie, who has reported on CV risk in patients with PsA. “Relative to what the patient’s perceived risk is, they may be treated similarly (to the general population). But relative to their actual risk, they’re undertreated.”
The 2019 AAD-NPF psoriasis guidelines recommend utilizing a 1.5 multiplication factor in risk score models, such as the American College of Cardiology’s Atherosclerotic Cardiovascular Disease (ASCVD) Risk Estimator, when the patient has a body surface area >10% or is a candidate for systemic therapy or phototherapy.
Similarly, the 2018 American Heart Association (AHA)-ACC Guideline on the Management of Blood Cholesterol defines psoriasis, along with RA, metabolic syndrome, HIV, and other diseases, as a “cardiovascular risk enhancer” that should be factored into assessments of ASCVD risk. (The guideline does not specify a psoriasis severity threshold.)
“It’s the first time the specialty [of cardiology] has said, ‘pay attention to a skin disease,’ ” Dr. Gelfand said at the NPF meeting.
Using the 1.5 multiplication factor, a patient who otherwise would be classified in the AHA/ACC guideline as “borderline risk,” with a 10-year ASCVD risk of 5% to <7.5%, would instead have an “intermediate” 10-year ASCVD risk of ≥7.5% to <20%. Application of the AHA-ACC “risk enhancer” would have a similar effect.
For management, the main impact of psoriasis being considered a risk enhancer is that “it lowers the threshold for treatment with standard cardiovascular prevention medications such as statins.”
In general, “we should be taking a more aggressive approach to the management of traditional cardiovascular risk factors” in patients with psoriatic disease, he said. Instead of telling a patient with mildly elevated blood pressure, ‘I’ll see you in a year or two,’ or a patient entering a prediabetic stage to “watch what you eat, and I’ll see you in a couple of years,” clinicians need to be more vigilant.
“It’s about recognizing that these traditional cardiometabolic risk factors, synergistically with psoriasis, can start enhancing CV risk at an earlier age than we might expect,” said Dr. Garshick, whose 2021 review of CV risk in psoriasis describes how the inflammatory milieu in psoriasis is linked to atherosclerosis development.
Cardiologists are aware of this, but “many primary care physicians are not. It takes time for medical knowledge to diffuse,” Dr. Gelfand said. “Tell the PCP, in notes or in a form letter, that there is a higher risk of CV disease, and reference the AHA/ACC guidelines,” he advised. “You don’t want your patient to go to their doctor and the doctor to [be uninformed].”
‘Patients trust us’
Dr. Gelfand has been at the forefront of research on psoriasis and heart disease. A study he coauthored in 2006, for instance, documented an independent risk of MI, with adjusted relative risks of 1.29 and 3.10 for a 30-year-old patient with mild or severe disease, respectively, and higher risks for a 60-year-old. In 2010, he and coinvestigators found that severe psoriasis was an independent risk factor for CV mortality (HR, 1.57) after adjusting for age, sex, smoking, diabetes, hypertension, and hyperlipidemia.
Today, along with Dr. Barbieri, Dr. Ogdie, and others, he is studying the feasibility and efficacy of a proposed national, “centralized care coordinator” model of care whereby dermatologists and rheumatologists would educate the patient, order lipid and HbA1c measurements as medically appropriate, and then refer patients as needed to a care coordinator. The care coordinator would calculate a 10-year CVD risk score and counsel the patient on possible next steps.
In a pilot study of 85 patients at four sites, 92% of patients followed through on their physician’s recommendations to have labs drawn, and 86% indicated the model was acceptable and feasible. A total of 27% of patients had “newly identified, previously undiagnosed, elevated cardiovascular disease risk,” and exploratory effectiveness results indicated a successful reduction in predicted CVD risk in patients who started statins, Dr. Gelfand reported at the NPF meeting.
With funding from the NPF, a larger, single-arm, pragmatic “CP3” trial (NCT05908240) is enrolling 525 patients with psoriasis at 10-20 academic and nonacademic dermatology sites across the United States to further test the model. The primary endpoint will be the change in LDL cholesterol measured at 6 months among people with a 10-year risk ≥5%. Secondary endpoints will cover improvement in disease severity and quality of life, behavior modification, patient experience, and other issues.
“We have only 10-15 minutes [with patients] ... a care coordinator who is empathetic and understanding and [informed] could make a big difference,” Dr. Gelfand said at the NPF meeting. If findings are positive, the model would be tested in rheumatology sites as well. The hope, he said, is that the NPF would be able to fund an in-house care coordinator(s) for the long-term.
Notably, a patient survey conducted as part of exploratory research leading up to the care coordinator project showed that patients trust their dermatologist or rheumatologist for CVD education and screening. Among 160 patients with psoriasis and 162 patients with PsA, 76% and 90% agreed that “I would like it if my dermatologist/rheumatologist educated me about my risk of heart disease,” and 60% and 75%, respectively, agree that “it would be convenient for me to have my cholesterol checked by my dermatologist/rheumatologist.”
“Patients trust us,” Dr. Gelfand said at the NPF meeting. “And the pilot study shows us that patients are motivated.”
Taking an individualized, holistic, longitudinal approach
“Sometimes you do have to triage bit,” Dr. Gelfand said in an interview. “For a young person with normal body weight who doesn’t smoke and has mild psoriasis, one could just educate and advise that they see their primary care physician” for monitoring.
“But for the same patient who is obese, maybe smokes, and doesn’t have a primary care physician, I’d order labs,” he said. “You don’t want a patient walking out the door with an [undiagnosed] LDL of 160 or hypertension.”
Age is also an important consideration, as excess CVD risk associated with autoimmune diseases like psoriasis rises with age, Dr. Gelfand said during a seminar on psoriasis and PsA held at NYU Langone in December. For a young person, typically, “I need to focus on education and lifestyle … setting them on a healthy lifestyle trajectory,” he said. “Once they get to 40, from 40 to 75 or so, that’s a sweet spot for medical intervention to lower cardiovascular risk.”
Even at older ages, however, lipid management is not the be-all and end-all, he said in the interview. “We have to be holistic.”
One advantage of having highly successful therapies for psoriasis, and to a lesser extent PsA, is the time that becomes available during follow-up visits — once disease is under control — to “focus on other things,” he said. Waiting until disease is under control to discuss diet, exercise, or smoking, for instance, makes sense anyway, he said. “You don’t want to overwhelm patients with too much to do at once.”
Indeed, said dermatologist Robert E. Kalb, MD, of the Buffalo Medical Group in Buffalo, NY, “patients have an open mind [about discussing cardiovascular disease risk], but it is not high on their radar. Most of them just want to get their skin clear.” (Dr. Kalb participated in the care coordinator pilot study, and said in an interview that since its completion, he has been more routinely ordering relevant labs.)
Rheumatologists are less fortunate with highly successful therapies, but “over the continuum of care, we do have time in office visits” to discuss issues like smoking, exercise, and lifestyle, Dr. Ogdie said. “I think of each of those pieces as part of our job.”
In the future, as researchers learn more about the impact of psoriasis and PsA treatments on CVD risk, it may be possible to tailor treatments or to prescribe treatments knowing that the therapies could reduce risk. Observational and epidemiologic data suggest that tumor necrosis factor-alpha inhibitor therapy over 3 years reduces the risk of MI, and that patients whose psoriasis is treated have reduced aortic inflammation, improved myocardial strain, and reduced coronary plaque burden, Dr. Garshick said at the NPF meeting.
“But when we look at the randomized controlled trials, they’re actually inconclusive that targeting inflammation in psoriatic disease reduces surrogates of cardiovascular disease,” he said. Dr. Garshick’s own research focuses on platelet and endothelial biology in psoriasis.
Dr. Barbieri reported he had no relevant disclosures. Dr. Garshick reported consulting fees from Bristol-Myers Squibb, Kiniksa, Horizon Therapeutics, and Agepha. Dr. Ogdie reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Takeda, and UCB. Dr. Gelfand reported serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, GlaxoSmithKline, and other companies.
Cluster of Eye Syphilis Cases Prompts CDC Concern
, according to a report by the Centers for Disease Control and Prevention.
With the incidence of syphilis infection in women increasing in the United States, experts are asking clinicians to be on the lookout for unusual ocular presentations.
“This is the first time such a cluster has been reported in the US,” the International Society for Infectious Diseases posted on ProMED.
Five women in Southwest Michigan who had a common male sex partner developed syphilis infections in their eyes. No new cases have been found related to these five cases after the women and the man received medical care.
If left untreated, the bacterium, Treponema pallidum, can infect the eyes, the ears, and the central nervous system.
The women, identified as non-Hispanic White, were aged 40-60 years and were not infected with HIV. They were diagnosed with early-stage syphilis and all were hospitalized and treated with intravenous penicillin. Routes of sexual exposure among the women included anal (40%), oral (40%), and vaginal (100%), the report states.
The common male sex partner they all met online was found to have early latent syphilis but never developed ocular syphilis.
It is not the eyes that are being exposed. Rather, it is an ocular presentation brought about by a systemic infection carried through the bloodstream after sexual exposure, explains William Nettleton, MD, MPH, medical director of the Kalamazoo and Calhoun public health departments in Michigan and lead author of the report.
“If we screen, identify, and treat syphilis promptly, we can prevent systemic manifestations,” he says.
Clinicians should be aware that the ocular manifestations can come at different stages of syphilis. “For patients you think may have ocular syphilis,” Dr. Nettleton says, “an immediate ophthalmologic evaluation is indicated.”
Symptoms Differed
The five women presented with a variety of symptoms.
Multiple attempts to contact the male partner by telephone and text were made by Michigan Department of Health and Human Services, but he did not respond. Local public health physicians reviewed the man’s electronic health record and discovered that he had sought care at a hospital emergency department in January 2022 for ulcerative penile and anal lesions.
He reported having multiple female sex partners during the previous 12 months but declined to disclose their identities; he reported no male or transgender sexual contact, according to the CDC report. Eventually he agreed to an evaluation, was found to have early latent syphilis, and was treated with penicillin.
Cases of syphilis have been soaring in the United States in recent years, reaching a 70-year high.
A version of this article appeared on Medscape.com.
, according to a report by the Centers for Disease Control and Prevention.
With the incidence of syphilis infection in women increasing in the United States, experts are asking clinicians to be on the lookout for unusual ocular presentations.
“This is the first time such a cluster has been reported in the US,” the International Society for Infectious Diseases posted on ProMED.
Five women in Southwest Michigan who had a common male sex partner developed syphilis infections in their eyes. No new cases have been found related to these five cases after the women and the man received medical care.
If left untreated, the bacterium, Treponema pallidum, can infect the eyes, the ears, and the central nervous system.
The women, identified as non-Hispanic White, were aged 40-60 years and were not infected with HIV. They were diagnosed with early-stage syphilis and all were hospitalized and treated with intravenous penicillin. Routes of sexual exposure among the women included anal (40%), oral (40%), and vaginal (100%), the report states.
The common male sex partner they all met online was found to have early latent syphilis but never developed ocular syphilis.
It is not the eyes that are being exposed. Rather, it is an ocular presentation brought about by a systemic infection carried through the bloodstream after sexual exposure, explains William Nettleton, MD, MPH, medical director of the Kalamazoo and Calhoun public health departments in Michigan and lead author of the report.
“If we screen, identify, and treat syphilis promptly, we can prevent systemic manifestations,” he says.
Clinicians should be aware that the ocular manifestations can come at different stages of syphilis. “For patients you think may have ocular syphilis,” Dr. Nettleton says, “an immediate ophthalmologic evaluation is indicated.”
Symptoms Differed
The five women presented with a variety of symptoms.
Multiple attempts to contact the male partner by telephone and text were made by Michigan Department of Health and Human Services, but he did not respond. Local public health physicians reviewed the man’s electronic health record and discovered that he had sought care at a hospital emergency department in January 2022 for ulcerative penile and anal lesions.
He reported having multiple female sex partners during the previous 12 months but declined to disclose their identities; he reported no male or transgender sexual contact, according to the CDC report. Eventually he agreed to an evaluation, was found to have early latent syphilis, and was treated with penicillin.
Cases of syphilis have been soaring in the United States in recent years, reaching a 70-year high.
A version of this article appeared on Medscape.com.
, according to a report by the Centers for Disease Control and Prevention.
With the incidence of syphilis infection in women increasing in the United States, experts are asking clinicians to be on the lookout for unusual ocular presentations.
“This is the first time such a cluster has been reported in the US,” the International Society for Infectious Diseases posted on ProMED.
Five women in Southwest Michigan who had a common male sex partner developed syphilis infections in their eyes. No new cases have been found related to these five cases after the women and the man received medical care.
If left untreated, the bacterium, Treponema pallidum, can infect the eyes, the ears, and the central nervous system.
The women, identified as non-Hispanic White, were aged 40-60 years and were not infected with HIV. They were diagnosed with early-stage syphilis and all were hospitalized and treated with intravenous penicillin. Routes of sexual exposure among the women included anal (40%), oral (40%), and vaginal (100%), the report states.
The common male sex partner they all met online was found to have early latent syphilis but never developed ocular syphilis.
It is not the eyes that are being exposed. Rather, it is an ocular presentation brought about by a systemic infection carried through the bloodstream after sexual exposure, explains William Nettleton, MD, MPH, medical director of the Kalamazoo and Calhoun public health departments in Michigan and lead author of the report.
“If we screen, identify, and treat syphilis promptly, we can prevent systemic manifestations,” he says.
Clinicians should be aware that the ocular manifestations can come at different stages of syphilis. “For patients you think may have ocular syphilis,” Dr. Nettleton says, “an immediate ophthalmologic evaluation is indicated.”
Symptoms Differed
The five women presented with a variety of symptoms.
Multiple attempts to contact the male partner by telephone and text were made by Michigan Department of Health and Human Services, but he did not respond. Local public health physicians reviewed the man’s electronic health record and discovered that he had sought care at a hospital emergency department in January 2022 for ulcerative penile and anal lesions.
He reported having multiple female sex partners during the previous 12 months but declined to disclose their identities; he reported no male or transgender sexual contact, according to the CDC report. Eventually he agreed to an evaluation, was found to have early latent syphilis, and was treated with penicillin.
Cases of syphilis have been soaring in the United States in recent years, reaching a 70-year high.
A version of this article appeared on Medscape.com.
FROM MMWR
Bilateral Burning Palmoplantar Lesions
The Diagnosis: Lichen Sclerosus
Histopathology revealed a thin epidermis with homogenization of the upper dermal collagen. By contrast, the lower dermis was sclerotic with patchy chronic dermal infiltrate (Figure). Ultimately, the patient’s clinical presentation and histopathologic findings led to a diagnosis of lichen sclerosus (LS).
Lichen sclerosus is a rare chronic inflammatory skin condition that typically is characterized by porcelainwhite atrophic plaques on the skin, most often involving the external female genitalia including the vulva and perianal area.1 It is thought to be underdiagnosed and underreported.2 Extragenital manifestations may occur, though some cases are characterized by concomitant genital involvement.3,4 Our patient presented with palmoplantar distribution of plaques without genitalia involvement. Approximately 6% to 10% of patients with extragenital LS do not have genital involvement at the time of diagnosis.3,5 Furthermore, LS involving the palms and soles is exceedingly rare.2 Although extragenital LS may be asymptomatic, patients can experience debilitating pruritus; bullae with hemorrhage and erosion; plaque thickening with repeated excoriations; and painful fissuring, especially if lesions are in areas that are susceptible to friction or tension.3,6 New lesions on previously unaffected skin also may develop secondary to trauma through the Koebner phenomenon.1,6
Histologically, LS is characterized by epidermal hyperkeratosis accompanied by follicular plugging, epidermal atrophy with flattened rete ridges, vacuolization of the basal epidermis, marked edema in the superficial dermis (in early lesions) or homogenized collagen in the upper dermis (in established lesions), and a lymphohistiocytic infiltrate beneath the homogenized collagen. Although the pathogenesis of LS is unclear, purported etiologic factors from studies in genital disease include immune dysfunction, genetic predisposition, infection, and trauma.6 Lichen sclerosus is associated strongly with autoimmune diseases including alopecia areata, vitiligo, autoimmune thyroiditis, diabetes mellitus, and pernicious anemia, indicating its potential multifactorial etiology and linkage to T-lymphocyte dysfunction.1 Early LS lesions often appear as flat-topped and slightly scaly, hypopigmented, white or mildly erythematous, polygonal papules that coalesce to form larger plaques with peripheral erythema. With time, the inflammation subsides, and lesions become porcelain-white with varying degrees of palpable sclerosis, resembling thin paperlike wrinkles indicative of epidermal atrophy.6
The differential diagnosis of LS includes lichen planus (LP), morphea, discoid lupus erythematosus (DLE), and vitiligo.3 Lesions of LP commonly are described as flat-topped, polygonal, pink-purple papules localized mostly along the volar wrists, shins, presacral area, and hands.7 Lichen planus is considered to be more pruritic3 than LS and can be further distinguished by biopsy through identifying a well-formed granular layer and numerous cytoid bodies. Unlike LS, LP is not characterized by basement membrane thickening or epidermal atrophy.8
Skin lesions seen in morphea may resemble the classic atrophic white lesions of extragenital LS; however, it is unclear if the appearance of LS-like lesions with morphea is a simultaneous occurrence of 2 separate disorders or the development of clinical findings resembling LS in lesions of morphea.6 Furthermore, morphea involves deep inflammation and sclerosis of the dermis that may extend into subcutaneous fat without follicular plugging of the epidermis.3,9 In contrast, LS primarily affects the epidermis and dermis with the presence of epidermal follicular plugging.6
Lesions seen in DLE are characterized as well-defined, annular, erythematous patches and plaques followed by follicular hyperkeratosis with adherent scaling. Upon removal of the scale, follicle-sized keratotic spikes (carpet tacks) are present.10 Scaling of lesions and the carpet tack sign were absent in our patient. In addition, DLE typically reveals surrounding pigmentation and scarring over plaques,3 which were not observed in our patient.
Vitiligo commonly is associated with extragenital LS. As with LS, vitiligo can be explained by mechanisms of immune checkpoint inhibitor–induced cytotoxicity as well as perforin and granzyme-B expression.11 Although vitiligo resembles the late hypopigmented lesions of extragenital LS, there are no plaques or surface changes, and a larger, more generalized area of the skin typically is involved.3
- Chamli A, Souissi A. Lichen sclerosus. StatPearls [Internet]. StatPearls Publishing; 2022. http://www.ncbi.nlm.nih.gov/books/NBK538246/
- Gaddis KJ, Huang J, Haun PL. An atrophic and spiny eruption of the palms. JAMA Dermatol. 2018;154:1344-1345. doi:10.1001 /jamadermatol.2018.1265
- Arif T, Fatima R, Sami M. Extragenital lichen sclerosus: a comprehensive review [published online August 11, 2022]. Australas J Dermatol. doi:10.1111/ajd.13890
- Heibel HD, Styles AR, Cockerell CJ. A case of acral lichen sclerosus et atrophicus. JAAD Case Rep. 2020;8:26-27. doi:10.1016/j.jdcr.2020.12.008
- Seyffert J, Bibliowicz N, Harding T, et al. Palmar lichen sclerosus et atrophicus. JAAD Case Rep. 2020;6:697-699. doi:10.1016/j.jdcr.2020.06.005
- Jacobe H. Extragenital lichen sclerosus: clinical features and diagnosis. UpToDate. Updated July 11, 2023. Accessed December 14, 2023. https://www.uptodate.com/contents/extragenital-lichen-sclerosus?search=Lichen%20sclerosus&source =search_result&selectedTitle=2~66&usage_type=default&display_ rank=2
- Goldstein BG, Goldstein AO, Mostow E. Lichen planus. UpToDate. Updated October 25, 2021. Accessed December 14, 2023. https://www.uptodate.com/contents/lichen-planus?search=lichen%20 sclerosus&topicRef=15838&source=see_link
- Tallon B. Lichen sclerosus pathology. DermNet NZ website. Accessed December 5, 2023. https://dermnetnz.org/topics/lichen-sclerosus-pathology
- Jacobe H. Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults. UpToDate. Updated November 15, 2021. Accessed December 14, 2023. https://medilib.ir/uptodate/show/13776
- McDaniel B, Sukumaran S, Koritala T, et al. Discoid lupus erythematosus. StatPearls [Internet]. StatPearls Publishing; 2022. Updated August 28, 2023. Accessed December 14, 2023. http://www.ncbi.nlm.nih.gov/books/NBK493145/
- Veronesi G, Scarfì F, Misciali C, et al. An unusual skin reaction in uveal melanoma during treatment with nivolumab: extragenital lichen sclerosus. Anticancer Drugs. 2019;30:969-972. doi:10.1097/ CAD.0000000000000819
The Diagnosis: Lichen Sclerosus
Histopathology revealed a thin epidermis with homogenization of the upper dermal collagen. By contrast, the lower dermis was sclerotic with patchy chronic dermal infiltrate (Figure). Ultimately, the patient’s clinical presentation and histopathologic findings led to a diagnosis of lichen sclerosus (LS).
Lichen sclerosus is a rare chronic inflammatory skin condition that typically is characterized by porcelainwhite atrophic plaques on the skin, most often involving the external female genitalia including the vulva and perianal area.1 It is thought to be underdiagnosed and underreported.2 Extragenital manifestations may occur, though some cases are characterized by concomitant genital involvement.3,4 Our patient presented with palmoplantar distribution of plaques without genitalia involvement. Approximately 6% to 10% of patients with extragenital LS do not have genital involvement at the time of diagnosis.3,5 Furthermore, LS involving the palms and soles is exceedingly rare.2 Although extragenital LS may be asymptomatic, patients can experience debilitating pruritus; bullae with hemorrhage and erosion; plaque thickening with repeated excoriations; and painful fissuring, especially if lesions are in areas that are susceptible to friction or tension.3,6 New lesions on previously unaffected skin also may develop secondary to trauma through the Koebner phenomenon.1,6
Histologically, LS is characterized by epidermal hyperkeratosis accompanied by follicular plugging, epidermal atrophy with flattened rete ridges, vacuolization of the basal epidermis, marked edema in the superficial dermis (in early lesions) or homogenized collagen in the upper dermis (in established lesions), and a lymphohistiocytic infiltrate beneath the homogenized collagen. Although the pathogenesis of LS is unclear, purported etiologic factors from studies in genital disease include immune dysfunction, genetic predisposition, infection, and trauma.6 Lichen sclerosus is associated strongly with autoimmune diseases including alopecia areata, vitiligo, autoimmune thyroiditis, diabetes mellitus, and pernicious anemia, indicating its potential multifactorial etiology and linkage to T-lymphocyte dysfunction.1 Early LS lesions often appear as flat-topped and slightly scaly, hypopigmented, white or mildly erythematous, polygonal papules that coalesce to form larger plaques with peripheral erythema. With time, the inflammation subsides, and lesions become porcelain-white with varying degrees of palpable sclerosis, resembling thin paperlike wrinkles indicative of epidermal atrophy.6
The differential diagnosis of LS includes lichen planus (LP), morphea, discoid lupus erythematosus (DLE), and vitiligo.3 Lesions of LP commonly are described as flat-topped, polygonal, pink-purple papules localized mostly along the volar wrists, shins, presacral area, and hands.7 Lichen planus is considered to be more pruritic3 than LS and can be further distinguished by biopsy through identifying a well-formed granular layer and numerous cytoid bodies. Unlike LS, LP is not characterized by basement membrane thickening or epidermal atrophy.8
Skin lesions seen in morphea may resemble the classic atrophic white lesions of extragenital LS; however, it is unclear if the appearance of LS-like lesions with morphea is a simultaneous occurrence of 2 separate disorders or the development of clinical findings resembling LS in lesions of morphea.6 Furthermore, morphea involves deep inflammation and sclerosis of the dermis that may extend into subcutaneous fat without follicular plugging of the epidermis.3,9 In contrast, LS primarily affects the epidermis and dermis with the presence of epidermal follicular plugging.6
Lesions seen in DLE are characterized as well-defined, annular, erythematous patches and plaques followed by follicular hyperkeratosis with adherent scaling. Upon removal of the scale, follicle-sized keratotic spikes (carpet tacks) are present.10 Scaling of lesions and the carpet tack sign were absent in our patient. In addition, DLE typically reveals surrounding pigmentation and scarring over plaques,3 which were not observed in our patient.
Vitiligo commonly is associated with extragenital LS. As with LS, vitiligo can be explained by mechanisms of immune checkpoint inhibitor–induced cytotoxicity as well as perforin and granzyme-B expression.11 Although vitiligo resembles the late hypopigmented lesions of extragenital LS, there are no plaques or surface changes, and a larger, more generalized area of the skin typically is involved.3
The Diagnosis: Lichen Sclerosus
Histopathology revealed a thin epidermis with homogenization of the upper dermal collagen. By contrast, the lower dermis was sclerotic with patchy chronic dermal infiltrate (Figure). Ultimately, the patient’s clinical presentation and histopathologic findings led to a diagnosis of lichen sclerosus (LS).
Lichen sclerosus is a rare chronic inflammatory skin condition that typically is characterized by porcelainwhite atrophic plaques on the skin, most often involving the external female genitalia including the vulva and perianal area.1 It is thought to be underdiagnosed and underreported.2 Extragenital manifestations may occur, though some cases are characterized by concomitant genital involvement.3,4 Our patient presented with palmoplantar distribution of plaques without genitalia involvement. Approximately 6% to 10% of patients with extragenital LS do not have genital involvement at the time of diagnosis.3,5 Furthermore, LS involving the palms and soles is exceedingly rare.2 Although extragenital LS may be asymptomatic, patients can experience debilitating pruritus; bullae with hemorrhage and erosion; plaque thickening with repeated excoriations; and painful fissuring, especially if lesions are in areas that are susceptible to friction or tension.3,6 New lesions on previously unaffected skin also may develop secondary to trauma through the Koebner phenomenon.1,6
Histologically, LS is characterized by epidermal hyperkeratosis accompanied by follicular plugging, epidermal atrophy with flattened rete ridges, vacuolization of the basal epidermis, marked edema in the superficial dermis (in early lesions) or homogenized collagen in the upper dermis (in established lesions), and a lymphohistiocytic infiltrate beneath the homogenized collagen. Although the pathogenesis of LS is unclear, purported etiologic factors from studies in genital disease include immune dysfunction, genetic predisposition, infection, and trauma.6 Lichen sclerosus is associated strongly with autoimmune diseases including alopecia areata, vitiligo, autoimmune thyroiditis, diabetes mellitus, and pernicious anemia, indicating its potential multifactorial etiology and linkage to T-lymphocyte dysfunction.1 Early LS lesions often appear as flat-topped and slightly scaly, hypopigmented, white or mildly erythematous, polygonal papules that coalesce to form larger plaques with peripheral erythema. With time, the inflammation subsides, and lesions become porcelain-white with varying degrees of palpable sclerosis, resembling thin paperlike wrinkles indicative of epidermal atrophy.6
The differential diagnosis of LS includes lichen planus (LP), morphea, discoid lupus erythematosus (DLE), and vitiligo.3 Lesions of LP commonly are described as flat-topped, polygonal, pink-purple papules localized mostly along the volar wrists, shins, presacral area, and hands.7 Lichen planus is considered to be more pruritic3 than LS and can be further distinguished by biopsy through identifying a well-formed granular layer and numerous cytoid bodies. Unlike LS, LP is not characterized by basement membrane thickening or epidermal atrophy.8
Skin lesions seen in morphea may resemble the classic atrophic white lesions of extragenital LS; however, it is unclear if the appearance of LS-like lesions with morphea is a simultaneous occurrence of 2 separate disorders or the development of clinical findings resembling LS in lesions of morphea.6 Furthermore, morphea involves deep inflammation and sclerosis of the dermis that may extend into subcutaneous fat without follicular plugging of the epidermis.3,9 In contrast, LS primarily affects the epidermis and dermis with the presence of epidermal follicular plugging.6
Lesions seen in DLE are characterized as well-defined, annular, erythematous patches and plaques followed by follicular hyperkeratosis with adherent scaling. Upon removal of the scale, follicle-sized keratotic spikes (carpet tacks) are present.10 Scaling of lesions and the carpet tack sign were absent in our patient. In addition, DLE typically reveals surrounding pigmentation and scarring over plaques,3 which were not observed in our patient.
Vitiligo commonly is associated with extragenital LS. As with LS, vitiligo can be explained by mechanisms of immune checkpoint inhibitor–induced cytotoxicity as well as perforin and granzyme-B expression.11 Although vitiligo resembles the late hypopigmented lesions of extragenital LS, there are no plaques or surface changes, and a larger, more generalized area of the skin typically is involved.3
- Chamli A, Souissi A. Lichen sclerosus. StatPearls [Internet]. StatPearls Publishing; 2022. http://www.ncbi.nlm.nih.gov/books/NBK538246/
- Gaddis KJ, Huang J, Haun PL. An atrophic and spiny eruption of the palms. JAMA Dermatol. 2018;154:1344-1345. doi:10.1001 /jamadermatol.2018.1265
- Arif T, Fatima R, Sami M. Extragenital lichen sclerosus: a comprehensive review [published online August 11, 2022]. Australas J Dermatol. doi:10.1111/ajd.13890
- Heibel HD, Styles AR, Cockerell CJ. A case of acral lichen sclerosus et atrophicus. JAAD Case Rep. 2020;8:26-27. doi:10.1016/j.jdcr.2020.12.008
- Seyffert J, Bibliowicz N, Harding T, et al. Palmar lichen sclerosus et atrophicus. JAAD Case Rep. 2020;6:697-699. doi:10.1016/j.jdcr.2020.06.005
- Jacobe H. Extragenital lichen sclerosus: clinical features and diagnosis. UpToDate. Updated July 11, 2023. Accessed December 14, 2023. https://www.uptodate.com/contents/extragenital-lichen-sclerosus?search=Lichen%20sclerosus&source =search_result&selectedTitle=2~66&usage_type=default&display_ rank=2
- Goldstein BG, Goldstein AO, Mostow E. Lichen planus. UpToDate. Updated October 25, 2021. Accessed December 14, 2023. https://www.uptodate.com/contents/lichen-planus?search=lichen%20 sclerosus&topicRef=15838&source=see_link
- Tallon B. Lichen sclerosus pathology. DermNet NZ website. Accessed December 5, 2023. https://dermnetnz.org/topics/lichen-sclerosus-pathology
- Jacobe H. Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults. UpToDate. Updated November 15, 2021. Accessed December 14, 2023. https://medilib.ir/uptodate/show/13776
- McDaniel B, Sukumaran S, Koritala T, et al. Discoid lupus erythematosus. StatPearls [Internet]. StatPearls Publishing; 2022. Updated August 28, 2023. Accessed December 14, 2023. http://www.ncbi.nlm.nih.gov/books/NBK493145/
- Veronesi G, Scarfì F, Misciali C, et al. An unusual skin reaction in uveal melanoma during treatment with nivolumab: extragenital lichen sclerosus. Anticancer Drugs. 2019;30:969-972. doi:10.1097/ CAD.0000000000000819
- Chamli A, Souissi A. Lichen sclerosus. StatPearls [Internet]. StatPearls Publishing; 2022. http://www.ncbi.nlm.nih.gov/books/NBK538246/
- Gaddis KJ, Huang J, Haun PL. An atrophic and spiny eruption of the palms. JAMA Dermatol. 2018;154:1344-1345. doi:10.1001 /jamadermatol.2018.1265
- Arif T, Fatima R, Sami M. Extragenital lichen sclerosus: a comprehensive review [published online August 11, 2022]. Australas J Dermatol. doi:10.1111/ajd.13890
- Heibel HD, Styles AR, Cockerell CJ. A case of acral lichen sclerosus et atrophicus. JAAD Case Rep. 2020;8:26-27. doi:10.1016/j.jdcr.2020.12.008
- Seyffert J, Bibliowicz N, Harding T, et al. Palmar lichen sclerosus et atrophicus. JAAD Case Rep. 2020;6:697-699. doi:10.1016/j.jdcr.2020.06.005
- Jacobe H. Extragenital lichen sclerosus: clinical features and diagnosis. UpToDate. Updated July 11, 2023. Accessed December 14, 2023. https://www.uptodate.com/contents/extragenital-lichen-sclerosus?search=Lichen%20sclerosus&source =search_result&selectedTitle=2~66&usage_type=default&display_ rank=2
- Goldstein BG, Goldstein AO, Mostow E. Lichen planus. UpToDate. Updated October 25, 2021. Accessed December 14, 2023. https://www.uptodate.com/contents/lichen-planus?search=lichen%20 sclerosus&topicRef=15838&source=see_link
- Tallon B. Lichen sclerosus pathology. DermNet NZ website. Accessed December 5, 2023. https://dermnetnz.org/topics/lichen-sclerosus-pathology
- Jacobe H. Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults. UpToDate. Updated November 15, 2021. Accessed December 14, 2023. https://medilib.ir/uptodate/show/13776
- McDaniel B, Sukumaran S, Koritala T, et al. Discoid lupus erythematosus. StatPearls [Internet]. StatPearls Publishing; 2022. Updated August 28, 2023. Accessed December 14, 2023. http://www.ncbi.nlm.nih.gov/books/NBK493145/
- Veronesi G, Scarfì F, Misciali C, et al. An unusual skin reaction in uveal melanoma during treatment with nivolumab: extragenital lichen sclerosus. Anticancer Drugs. 2019;30:969-972. doi:10.1097/ CAD.0000000000000819
A 59-year-old woman presented with atrophic, hypopigmented, ivory papules and plaques localized to the central palms and soles of 3 years’ duration. The lesions were associated with burning that was most notable after extended periods of ambulation. The lesions initially were diagnosed as plaque psoriasis by an external dermatology clinic. At the time of presentation to our clinic, treatment with several highpotency topical steroids and biologics approved for plaque psoriasis had failed. Her medical history and concurrent medical workup were notable for type 2 diabetes mellitus, liver dysfunction, thyroid nodules overseen by an endocrinologist, vitamin B12 and vitamin D deficiencies managed with supplementation, and diffuse androgenic alopecia with suspected telogen effluvium. Physical examination revealed no plaque fissuring, pruritus, or scaling. She had no history of radiation therapy or organ transplantation. A punch biopsy of the left palm was performed.
Alcohol and CV Risk: Both Beneficial and Harmful Effects?
with evidence emerging that alcohol use may both increase and decrease the risk for CVD.
The answer may depend on the presence of circulating metabolites of alcohol, some of which may be beneficial while others may be harmful, new research suggests.
“We adopted an association analysis, looking at 60 metabolites produced during or after alcohol has been metabolized, to see whether those metabolites can link alcohol consumption with CVD,” senior author Jiantao Ma, PhD, MBBS, assistant professor, Division of Nutrition Epidemiology and Data Science, Friedman School, Tufts University, Boston, Massachusetts, said in an interview.
“We found that the relationship is quite complex, with some metabolites showing protective effects against CVD and others showing harmful effects,” said Dr. Ma. “This opens the door for future research because we think that these molecules can help [us] understand the mechanism of the relationship between alcohol and CVD.”
The study was published online in BMC Medicine.
J-Shaped Relationship?
Previous research has painted a confusing picture of the relationship between alcohol consumption and CVD. For example, some studies have suggested that moderate levels of drinking may be hazardous to cardiac health, while others have pointed to potential cardioprotective effects.
Nevertheless, “according to the latest ACC/AHA guidelines regarding alcohol consumption and its relationship to CVD, there is no level of alcohol use that is deemed safe and considered acceptable,” Saurabh Sharma, MD, program director, Internal Medicine Residency Program, and clinical assistant professor of cardiology, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, said in an interview.
Older observational data suggested a “J-shaped” relationship between alcohol consumption and cardiovascular risk, such that a low to moderate amount might reduce risk, while higher amounts increase it, said Dr. Sharma, a member of the American College of Cardiology (ACC) Prevention of Cardiovascular Diseases Council.
“But it’s essential to note that these findings were based on observational studies. No randomized controlled trials have provided conclusive evidence supporting the idea that moderate alcohol consumption actively reduces cardiovascular risk,” he said.
The current study is also observational, but it shines a somewhat different spotlight on the subject by examining alcohol consumption–related metabolites, said Dr. Ma — that is, small molecules that are the intermediates or end-products of metabolism in many cellular processes.
Some recent research “shows that alcohol may be harmful or at least has no beneficial effect in CVD prevention,” he said. “Our motivation was to analyze the association using metabolites, genetics, and epigenetics, because we think that these molecules may help us understand some of the mechanisms that underlie the relationship between alcohol consumption and CVD, and partially answer the question of whether alcohol may be harmful or helpful.”
Caution Warranted
Although some previous studies have looked at metabolites, most analyzed alcohol consumption measured at a single time point, “which may not represent habitual or long-term alcohol consumption,” the researchers note.
The team used data derived from 2458 Framingham Heart Study Offspring participants (mean age, 56 ± 9.3 years at the fifth examination; 52% female), calculating the cumulative average alcohol consumption from total intake of beer, wine, and liquor over an average 20-year period. Most participants were overweight, close to one fifth were current smokers, and 636 developed CVD over the study period.
Participants were assessed every 4-8 years, with metabolites measured during the fifth examination.
Linear models were used to investigate the association of alcohol consumption with 211 plasma metabolites, adjusting for a variety of potential confounders, including age, sex, batch, smoking, diet, physical activity, body mass index, and familial relationship.
Sixty metabolites associated with cumulative average alcohol consumption were identified (P < .00024), after adjustment for confounders. Of these, 40 displayed positive associations with the cumulative average alcohol consumption, with the most significant metabolite being cholesteryl palmitoleate (CE16:1), a plasma cholesteryl ester involved with cholesterol metabolism.
One gram per day of higher alcohol consumption was associated with a higher-level CE16:1 in the blood (b = .023). Several other phosphatidylcholine metabolites were also positively associated with alcohol consumption.
On the other hand, 20 metabolites were negatively associated with alcohol consumption, with triacylglycerol 54:4 (TAG 54:4) displaying the most significant association (b = –.017).
The alcoholic beverages were not equal when it came to association with metabolites: 19 metabolites were significantly associated with the cumulative average consumption of beer, 30 with wine, and 32 with liquor. Seven were significantly associated with the cumulative consumption of all three types of drinks.
The researchers conducted survival analysis that identified 10 alcohol-associated metabolites associated with differential CVD risks, after adjusting for confounders. They also built two alcohol consumption–weighted metabolite scores using these 10 metabolites. After adjustment for confounders including CVD risk factors, the two scores had “comparable but opposite” associations with incident CVD, HR 1.11 (95% CI, 1.02-1.21) vs 0.88 (0.78-0.98; both P values = .02).
“We found that seven metabolites were harmful, while three were beneficial, “ Dr. Ma reported.
Dr. Ma cautioned that association “doesn’t represent causation.” On the basis of the findings, however, “we can hypothesize that if you drink a moderate amount of alcohol, you can either increase or decrease your risk of CVD.”
For people with cardiac conditions, “it would be [wise to be] cautious in recommending alcohol consumption,” he said. “For people without cardiac conditions, I would follow the recommendations of the AHA. If people don’t already drink alcohol, we don’t recommend that you start drinking it; and if you already drink, we’d recommend keeping it minimal.”
He cautioned that this is “only one study and we need more research if we are to generate a clearer message to the patient.” At present, perhaps the best message to patients is “to be cautious and warn them that there are potentially harmful effects,” he said.
Mendelian Randomization?
Dr. Sharma, who was not involved in the study, emphasized that it’s “crucial” to recognize that the study “does not alter the established understanding that any level of alcohol consumption poses harm to the heart,” and that “any amount of alcohol consumption has the potential to elevate triglyceride levels, thereby contributing to the increased risk of cardiovascular complications.”
Previously reported cardioprotective benefits “are likely influenced by confounding factors, such as lifestyle and sociodemographic elements,” he speculated.
He noted that observational studies “encounter challenges in disentangling the influence of factors like obesity, lack of exercise, and tobacco use” as well as reverse causality.
“To overcome these limitations, Mendelian randomization emerges as a robust method,” he suggested. “This approach utilizes measured genetic variations with known functions to investigate the causal effect of a modifiable exposure on disease within the framework of observational studies.”
Notably, certain studies using this approach, including one by Larsson and colleagues, and another by Biddinger and associates, “have provided valuable insights by establishing a clear and causal relationship between alcohol consumption and CVD,” he said.
The study was funded by the National Institute of Health’s National Institute on Alcohol Abuse and Alcoholism. Data collection in the Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute. Dr. Ma and coauthors and Dr. Sharma disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
with evidence emerging that alcohol use may both increase and decrease the risk for CVD.
The answer may depend on the presence of circulating metabolites of alcohol, some of which may be beneficial while others may be harmful, new research suggests.
“We adopted an association analysis, looking at 60 metabolites produced during or after alcohol has been metabolized, to see whether those metabolites can link alcohol consumption with CVD,” senior author Jiantao Ma, PhD, MBBS, assistant professor, Division of Nutrition Epidemiology and Data Science, Friedman School, Tufts University, Boston, Massachusetts, said in an interview.
“We found that the relationship is quite complex, with some metabolites showing protective effects against CVD and others showing harmful effects,” said Dr. Ma. “This opens the door for future research because we think that these molecules can help [us] understand the mechanism of the relationship between alcohol and CVD.”
The study was published online in BMC Medicine.
J-Shaped Relationship?
Previous research has painted a confusing picture of the relationship between alcohol consumption and CVD. For example, some studies have suggested that moderate levels of drinking may be hazardous to cardiac health, while others have pointed to potential cardioprotective effects.
Nevertheless, “according to the latest ACC/AHA guidelines regarding alcohol consumption and its relationship to CVD, there is no level of alcohol use that is deemed safe and considered acceptable,” Saurabh Sharma, MD, program director, Internal Medicine Residency Program, and clinical assistant professor of cardiology, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, said in an interview.
Older observational data suggested a “J-shaped” relationship between alcohol consumption and cardiovascular risk, such that a low to moderate amount might reduce risk, while higher amounts increase it, said Dr. Sharma, a member of the American College of Cardiology (ACC) Prevention of Cardiovascular Diseases Council.
“But it’s essential to note that these findings were based on observational studies. No randomized controlled trials have provided conclusive evidence supporting the idea that moderate alcohol consumption actively reduces cardiovascular risk,” he said.
The current study is also observational, but it shines a somewhat different spotlight on the subject by examining alcohol consumption–related metabolites, said Dr. Ma — that is, small molecules that are the intermediates or end-products of metabolism in many cellular processes.
Some recent research “shows that alcohol may be harmful or at least has no beneficial effect in CVD prevention,” he said. “Our motivation was to analyze the association using metabolites, genetics, and epigenetics, because we think that these molecules may help us understand some of the mechanisms that underlie the relationship between alcohol consumption and CVD, and partially answer the question of whether alcohol may be harmful or helpful.”
Caution Warranted
Although some previous studies have looked at metabolites, most analyzed alcohol consumption measured at a single time point, “which may not represent habitual or long-term alcohol consumption,” the researchers note.
The team used data derived from 2458 Framingham Heart Study Offspring participants (mean age, 56 ± 9.3 years at the fifth examination; 52% female), calculating the cumulative average alcohol consumption from total intake of beer, wine, and liquor over an average 20-year period. Most participants were overweight, close to one fifth were current smokers, and 636 developed CVD over the study period.
Participants were assessed every 4-8 years, with metabolites measured during the fifth examination.
Linear models were used to investigate the association of alcohol consumption with 211 plasma metabolites, adjusting for a variety of potential confounders, including age, sex, batch, smoking, diet, physical activity, body mass index, and familial relationship.
Sixty metabolites associated with cumulative average alcohol consumption were identified (P < .00024), after adjustment for confounders. Of these, 40 displayed positive associations with the cumulative average alcohol consumption, with the most significant metabolite being cholesteryl palmitoleate (CE16:1), a plasma cholesteryl ester involved with cholesterol metabolism.
One gram per day of higher alcohol consumption was associated with a higher-level CE16:1 in the blood (b = .023). Several other phosphatidylcholine metabolites were also positively associated with alcohol consumption.
On the other hand, 20 metabolites were negatively associated with alcohol consumption, with triacylglycerol 54:4 (TAG 54:4) displaying the most significant association (b = –.017).
The alcoholic beverages were not equal when it came to association with metabolites: 19 metabolites were significantly associated with the cumulative average consumption of beer, 30 with wine, and 32 with liquor. Seven were significantly associated with the cumulative consumption of all three types of drinks.
The researchers conducted survival analysis that identified 10 alcohol-associated metabolites associated with differential CVD risks, after adjusting for confounders. They also built two alcohol consumption–weighted metabolite scores using these 10 metabolites. After adjustment for confounders including CVD risk factors, the two scores had “comparable but opposite” associations with incident CVD, HR 1.11 (95% CI, 1.02-1.21) vs 0.88 (0.78-0.98; both P values = .02).
“We found that seven metabolites were harmful, while three were beneficial, “ Dr. Ma reported.
Dr. Ma cautioned that association “doesn’t represent causation.” On the basis of the findings, however, “we can hypothesize that if you drink a moderate amount of alcohol, you can either increase or decrease your risk of CVD.”
For people with cardiac conditions, “it would be [wise to be] cautious in recommending alcohol consumption,” he said. “For people without cardiac conditions, I would follow the recommendations of the AHA. If people don’t already drink alcohol, we don’t recommend that you start drinking it; and if you already drink, we’d recommend keeping it minimal.”
He cautioned that this is “only one study and we need more research if we are to generate a clearer message to the patient.” At present, perhaps the best message to patients is “to be cautious and warn them that there are potentially harmful effects,” he said.
Mendelian Randomization?
Dr. Sharma, who was not involved in the study, emphasized that it’s “crucial” to recognize that the study “does not alter the established understanding that any level of alcohol consumption poses harm to the heart,” and that “any amount of alcohol consumption has the potential to elevate triglyceride levels, thereby contributing to the increased risk of cardiovascular complications.”
Previously reported cardioprotective benefits “are likely influenced by confounding factors, such as lifestyle and sociodemographic elements,” he speculated.
He noted that observational studies “encounter challenges in disentangling the influence of factors like obesity, lack of exercise, and tobacco use” as well as reverse causality.
“To overcome these limitations, Mendelian randomization emerges as a robust method,” he suggested. “This approach utilizes measured genetic variations with known functions to investigate the causal effect of a modifiable exposure on disease within the framework of observational studies.”
Notably, certain studies using this approach, including one by Larsson and colleagues, and another by Biddinger and associates, “have provided valuable insights by establishing a clear and causal relationship between alcohol consumption and CVD,” he said.
The study was funded by the National Institute of Health’s National Institute on Alcohol Abuse and Alcoholism. Data collection in the Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute. Dr. Ma and coauthors and Dr. Sharma disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
with evidence emerging that alcohol use may both increase and decrease the risk for CVD.
The answer may depend on the presence of circulating metabolites of alcohol, some of which may be beneficial while others may be harmful, new research suggests.
“We adopted an association analysis, looking at 60 metabolites produced during or after alcohol has been metabolized, to see whether those metabolites can link alcohol consumption with CVD,” senior author Jiantao Ma, PhD, MBBS, assistant professor, Division of Nutrition Epidemiology and Data Science, Friedman School, Tufts University, Boston, Massachusetts, said in an interview.
“We found that the relationship is quite complex, with some metabolites showing protective effects against CVD and others showing harmful effects,” said Dr. Ma. “This opens the door for future research because we think that these molecules can help [us] understand the mechanism of the relationship between alcohol and CVD.”
The study was published online in BMC Medicine.
J-Shaped Relationship?
Previous research has painted a confusing picture of the relationship between alcohol consumption and CVD. For example, some studies have suggested that moderate levels of drinking may be hazardous to cardiac health, while others have pointed to potential cardioprotective effects.
Nevertheless, “according to the latest ACC/AHA guidelines regarding alcohol consumption and its relationship to CVD, there is no level of alcohol use that is deemed safe and considered acceptable,” Saurabh Sharma, MD, program director, Internal Medicine Residency Program, and clinical assistant professor of cardiology, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, said in an interview.
Older observational data suggested a “J-shaped” relationship between alcohol consumption and cardiovascular risk, such that a low to moderate amount might reduce risk, while higher amounts increase it, said Dr. Sharma, a member of the American College of Cardiology (ACC) Prevention of Cardiovascular Diseases Council.
“But it’s essential to note that these findings were based on observational studies. No randomized controlled trials have provided conclusive evidence supporting the idea that moderate alcohol consumption actively reduces cardiovascular risk,” he said.
The current study is also observational, but it shines a somewhat different spotlight on the subject by examining alcohol consumption–related metabolites, said Dr. Ma — that is, small molecules that are the intermediates or end-products of metabolism in many cellular processes.
Some recent research “shows that alcohol may be harmful or at least has no beneficial effect in CVD prevention,” he said. “Our motivation was to analyze the association using metabolites, genetics, and epigenetics, because we think that these molecules may help us understand some of the mechanisms that underlie the relationship between alcohol consumption and CVD, and partially answer the question of whether alcohol may be harmful or helpful.”
Caution Warranted
Although some previous studies have looked at metabolites, most analyzed alcohol consumption measured at a single time point, “which may not represent habitual or long-term alcohol consumption,” the researchers note.
The team used data derived from 2458 Framingham Heart Study Offspring participants (mean age, 56 ± 9.3 years at the fifth examination; 52% female), calculating the cumulative average alcohol consumption from total intake of beer, wine, and liquor over an average 20-year period. Most participants were overweight, close to one fifth were current smokers, and 636 developed CVD over the study period.
Participants were assessed every 4-8 years, with metabolites measured during the fifth examination.
Linear models were used to investigate the association of alcohol consumption with 211 plasma metabolites, adjusting for a variety of potential confounders, including age, sex, batch, smoking, diet, physical activity, body mass index, and familial relationship.
Sixty metabolites associated with cumulative average alcohol consumption were identified (P < .00024), after adjustment for confounders. Of these, 40 displayed positive associations with the cumulative average alcohol consumption, with the most significant metabolite being cholesteryl palmitoleate (CE16:1), a plasma cholesteryl ester involved with cholesterol metabolism.
One gram per day of higher alcohol consumption was associated with a higher-level CE16:1 in the blood (b = .023). Several other phosphatidylcholine metabolites were also positively associated with alcohol consumption.
On the other hand, 20 metabolites were negatively associated with alcohol consumption, with triacylglycerol 54:4 (TAG 54:4) displaying the most significant association (b = –.017).
The alcoholic beverages were not equal when it came to association with metabolites: 19 metabolites were significantly associated with the cumulative average consumption of beer, 30 with wine, and 32 with liquor. Seven were significantly associated with the cumulative consumption of all three types of drinks.
The researchers conducted survival analysis that identified 10 alcohol-associated metabolites associated with differential CVD risks, after adjusting for confounders. They also built two alcohol consumption–weighted metabolite scores using these 10 metabolites. After adjustment for confounders including CVD risk factors, the two scores had “comparable but opposite” associations with incident CVD, HR 1.11 (95% CI, 1.02-1.21) vs 0.88 (0.78-0.98; both P values = .02).
“We found that seven metabolites were harmful, while three were beneficial, “ Dr. Ma reported.
Dr. Ma cautioned that association “doesn’t represent causation.” On the basis of the findings, however, “we can hypothesize that if you drink a moderate amount of alcohol, you can either increase or decrease your risk of CVD.”
For people with cardiac conditions, “it would be [wise to be] cautious in recommending alcohol consumption,” he said. “For people without cardiac conditions, I would follow the recommendations of the AHA. If people don’t already drink alcohol, we don’t recommend that you start drinking it; and if you already drink, we’d recommend keeping it minimal.”
He cautioned that this is “only one study and we need more research if we are to generate a clearer message to the patient.” At present, perhaps the best message to patients is “to be cautious and warn them that there are potentially harmful effects,” he said.
Mendelian Randomization?
Dr. Sharma, who was not involved in the study, emphasized that it’s “crucial” to recognize that the study “does not alter the established understanding that any level of alcohol consumption poses harm to the heart,” and that “any amount of alcohol consumption has the potential to elevate triglyceride levels, thereby contributing to the increased risk of cardiovascular complications.”
Previously reported cardioprotective benefits “are likely influenced by confounding factors, such as lifestyle and sociodemographic elements,” he speculated.
He noted that observational studies “encounter challenges in disentangling the influence of factors like obesity, lack of exercise, and tobacco use” as well as reverse causality.
“To overcome these limitations, Mendelian randomization emerges as a robust method,” he suggested. “This approach utilizes measured genetic variations with known functions to investigate the causal effect of a modifiable exposure on disease within the framework of observational studies.”
Notably, certain studies using this approach, including one by Larsson and colleagues, and another by Biddinger and associates, “have provided valuable insights by establishing a clear and causal relationship between alcohol consumption and CVD,” he said.
The study was funded by the National Institute of Health’s National Institute on Alcohol Abuse and Alcoholism. Data collection in the Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute. Dr. Ma and coauthors and Dr. Sharma disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM BMC MEDICINE
Updates on Investigational Treatments for HR-Positive, HER2-Negative Breast Cancer
Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023.
A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD.
TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy
Study synopsis
Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial.
Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results:
In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)
At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent
In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients
In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively
At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd
The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.
EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging
Study synopsis
The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study.
Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate.
The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events:
The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)
The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)
The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).
In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment
In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus
In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib
Regarding efficacy:
The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively
The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively
Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer.
OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities
Study synopsis
OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.
Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date:
Grade 3 neutropenia occurred in 55% of participants
There were no grade 4 treatment-related adverse events and no dose-limiting toxicities
OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study
Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages
Investigators observed antitumor activity, including partial responses
Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation.
Conclusions
These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.
Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023.
A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD.
TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy
Study synopsis
Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial.
Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results:
In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)
At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent
In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients
In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively
At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd
The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.
EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging
Study synopsis
The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study.
Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate.
The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events:
The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)
The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)
The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).
In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment
In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus
In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib
Regarding efficacy:
The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively
The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively
Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer.
OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities
Study synopsis
OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.
Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date:
Grade 3 neutropenia occurred in 55% of participants
There were no grade 4 treatment-related adverse events and no dose-limiting toxicities
OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study
Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages
Investigators observed antitumor activity, including partial responses
Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation.
Conclusions
These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.
Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023.
A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD.
TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy
Study synopsis
Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial.
Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results:
In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)
At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent
In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients
In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively
At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd
The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.
EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging
Study synopsis
The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study.
Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate.
The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events:
The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)
The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)
The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).
In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment
In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus
In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib
Regarding efficacy:
The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively
The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively
Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer.
OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities
Study synopsis
OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.
Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date:
Grade 3 neutropenia occurred in 55% of participants
There were no grade 4 treatment-related adverse events and no dose-limiting toxicities
OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study
Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages
Investigators observed antitumor activity, including partial responses
Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation.
Conclusions
These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.
Bariatric surgery tied to less pregnancy weight gain
TOPLINE:
Pregnancy weight gain is lower in women with a history of gastric bypass or sleeve gastrectomy than in those without such a history, especially when the interval between surgery and conception is shorter, new data suggest.
METHODOLOGY:
- Using Swedish national registers, researchers investigated the association of pregnancy weight gain with history in 12,776 pregnancies — 6388 in women with a history of bariatric surgery and 6388 in women without such a history.
- Pregnancies were propensity score matched to patients’ early-pregnancy body mass index (BMI), prepregnancy diabetes, , smoking status, education, height, country of birth, and delivery year.
- Post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy.
- Time from surgery to conception was also assessed.
TAKEAWAY:
- Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls.
- The magnitude of difference was largest for women with normal weight or overweight early-pregnancy BMI status (adjusted mean difference in z score, −0.33), which then decreased stepwise within the subclasses (−0.21, −0.16, and −0.08 for obesity classes I, II, and III, respectively).
- Pregnancy weight gain did not differ by surgery type, but lower pregnancy weight gain was associated with a shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss.
IN PRACTICE:
“The highest proportion of weight gain below the recommendations was found among women with a normal weight status. Hence, clinical attention to women with history of bariatric surgery and a normal weight status in early pregnancy might be warranted,” the authors advised.
SOURCE:
The study, with the first author Huiling Xu, MD, MSc, Karolinska Institutet, Stockholm, Sweden, was published online in JAMA Network Open.
LIMITATIONS:
Despite rigorous matching, residual confounding was possible. The sample size was limited for some subgroups, possibly affecting statistical power. Although the study provides an overview of pregnancy outcomes within surgery-to-conception interval and pregnancy weight gain z scores, a more in-depth investigation is needed to understand the associations among bariatric surgery, pregnancy weight gain, and pregnancy outcomes.
DISCLOSURES:
Research for this study was supported by the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council. The authors have no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
Pregnancy weight gain is lower in women with a history of gastric bypass or sleeve gastrectomy than in those without such a history, especially when the interval between surgery and conception is shorter, new data suggest.
METHODOLOGY:
- Using Swedish national registers, researchers investigated the association of pregnancy weight gain with history in 12,776 pregnancies — 6388 in women with a history of bariatric surgery and 6388 in women without such a history.
- Pregnancies were propensity score matched to patients’ early-pregnancy body mass index (BMI), prepregnancy diabetes, , smoking status, education, height, country of birth, and delivery year.
- Post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy.
- Time from surgery to conception was also assessed.
TAKEAWAY:
- Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls.
- The magnitude of difference was largest for women with normal weight or overweight early-pregnancy BMI status (adjusted mean difference in z score, −0.33), which then decreased stepwise within the subclasses (−0.21, −0.16, and −0.08 for obesity classes I, II, and III, respectively).
- Pregnancy weight gain did not differ by surgery type, but lower pregnancy weight gain was associated with a shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss.
IN PRACTICE:
“The highest proportion of weight gain below the recommendations was found among women with a normal weight status. Hence, clinical attention to women with history of bariatric surgery and a normal weight status in early pregnancy might be warranted,” the authors advised.
SOURCE:
The study, with the first author Huiling Xu, MD, MSc, Karolinska Institutet, Stockholm, Sweden, was published online in JAMA Network Open.
LIMITATIONS:
Despite rigorous matching, residual confounding was possible. The sample size was limited for some subgroups, possibly affecting statistical power. Although the study provides an overview of pregnancy outcomes within surgery-to-conception interval and pregnancy weight gain z scores, a more in-depth investigation is needed to understand the associations among bariatric surgery, pregnancy weight gain, and pregnancy outcomes.
DISCLOSURES:
Research for this study was supported by the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council. The authors have no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
Pregnancy weight gain is lower in women with a history of gastric bypass or sleeve gastrectomy than in those without such a history, especially when the interval between surgery and conception is shorter, new data suggest.
METHODOLOGY:
- Using Swedish national registers, researchers investigated the association of pregnancy weight gain with history in 12,776 pregnancies — 6388 in women with a history of bariatric surgery and 6388 in women without such a history.
- Pregnancies were propensity score matched to patients’ early-pregnancy body mass index (BMI), prepregnancy diabetes, , smoking status, education, height, country of birth, and delivery year.
- Post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy.
- Time from surgery to conception was also assessed.
TAKEAWAY:
- Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls.
- The magnitude of difference was largest for women with normal weight or overweight early-pregnancy BMI status (adjusted mean difference in z score, −0.33), which then decreased stepwise within the subclasses (−0.21, −0.16, and −0.08 for obesity classes I, II, and III, respectively).
- Pregnancy weight gain did not differ by surgery type, but lower pregnancy weight gain was associated with a shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss.
IN PRACTICE:
“The highest proportion of weight gain below the recommendations was found among women with a normal weight status. Hence, clinical attention to women with history of bariatric surgery and a normal weight status in early pregnancy might be warranted,” the authors advised.
SOURCE:
The study, with the first author Huiling Xu, MD, MSc, Karolinska Institutet, Stockholm, Sweden, was published online in JAMA Network Open.
LIMITATIONS:
Despite rigorous matching, residual confounding was possible. The sample size was limited for some subgroups, possibly affecting statistical power. Although the study provides an overview of pregnancy outcomes within surgery-to-conception interval and pregnancy weight gain z scores, a more in-depth investigation is needed to understand the associations among bariatric surgery, pregnancy weight gain, and pregnancy outcomes.
DISCLOSURES:
Research for this study was supported by the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council. The authors have no relevant disclosures.
A version of this article appeared on Medscape.com.
Debate grows over facility fees as lawmakers urge greater transparency
Can the US healthcare system learn something about how to operate from car dealerships? Lawrence Kosinski, MD, MBA, a governing board member of American Gastroenterological Association (AGA), believes so.
There’s growing concern in the United States about the lack of clarity surrounding facility fees, which are intended to cover costs of maintaining medical facilities. Dr. Kosinski thinks that Congress should look into the transparency mandate it created for car prices as a model for how to address this.
A 1958 federal law set the stage for the consumer-friendly breakdown of costs and relevant performance data that anyone who has bought a new vehicle in the United States would recognize.
“You look at that and you know exactly what you are paying for,” Dr. Kosinski told this news organization. “In healthcare, we need something like that.”
Novel solutions like Dr. Kosinski’s will be increasingly necessary, as lawmakers on the state and federal level have begun to set their sights on tackling this issue.
The Biden administration in July expressed concern about an increased use of facility fees for healthcare provided at doctors’ offices, saying these additional costs often surprise consumers. House Energy and Commerce Chairwoman Cathy McMorris Rodgers (R-WA) also raised this issue several times this year, including at a May meeting about pending legislation on price transparency for health services, where she mentioned the case of a man who underwent eye surgery in Maine.
“His bill included three separate facility fees totaling $7800 and professional fees totaling $6200,” Ms. Rodgers said. “Why are three facility fees necessary for 1 hour of surgery in one O.R.?”
AGA’s Dr. Kosinski said facility fees cover the additional costs hospitals and clinics face in providing even routine treatments for some patients. For example, colonoscopy for a patient with a body mass index of 50 would pose special challenges for the anesthesiologist.
These factors need to be considered in setting policies on facility fees, he said. But there is no reason hospitals and other sites of medical care can’t make the information about facility fees easy for patients to find and understand, Dr. Kosinski said.
“I’m struggling to see a reason why we can’t be more transparent,” he said.
Big Battles Ahead
There are two connected battles ahead regarding facility fees: Efforts to restrict these additional charges for many medical services and fights over the need for greater transparency in general about health costs.
Senate Health, Education, Labor and Pensions Chairman Bernie Sanders (I-VT) is seeking to broadly restrict facility fees through his pending Primary Care and Health Workforce Act (S. 2840). The measure would block hospitals from charging health plans facility fees for many evaluation, management, and telehealth services.
The American Hospital Association (AHA) opposes it. They argue that the current payment approach rightly accounts for the added costs incurred when hospitals treat patients who are more likely to be ill or have chronic conditions than those seen in independent practices.
AHA said hospitals also need to maintain standby capacity for natural and man-made disasters, public health emergencies, and unexpected traumatic events. In September, AHA launched a television ad campaign to oppose any drive toward site-neutral policies. AHA says reducing the extra payments could cause more hospitals to shut their doors.
But there’s persistent interest in site-neutral payment, the term describing when the same reimbursement is given for care regardless of setting. This would lower pay for hospitals.
Among those pressing for change is an umbrella group of medical organizations known as the Alliance for Site Neutral Payment Reform. Its members include the American Academy of Family Physicians, American Academy of Orthopaedic Surgeons, American College of Physicians, Community Oncology Alliance, and Digestive Health Physicians Association.
And on November 9, Sen. Maggie Hassan (D-NH) argued for eventually including a site-neutral Medicare provision to a major healthcare package that the Senate Finance Committee is putting together.
Sen. Hassan is seeking to end what she called the “the practice of charging patients unfair hospital facility fees for care provided in the off-campus outpatient setting, like at a regular doctor’s office.”
Senate Finance Chairman Ron Wyden (D-OR) and the ranking Republican on the committee, Sen. Mike Crapo (R-ID), told Sen. Hassan they intended to work with her to see if this issue could be addressed in the pending legislative package.
A 2015 budget deal marked the last time Congress took a major step to address the higher cost of services provided in hospital-owned facilities.
Lawmakers then were scrambling to find cuts to offset spending in what became the 2015 Bipartisan Budget Act. This law established site-neutral payments under Medicare for services received at off-campus outpatient departments but exempted hospitals that already ran these kinds of operations or had advanced plans to create them.
Lawmakers are well aware of the potential savings from site-neutral policies and could look in time again to use them as part of a future budget deal.
In fact, in June, Sen. Hassan and Sens. Mike Braun (R-IN) and John Kennedy (R-LA) introduced a bill meant to basically end the exemption given in the 2015 deal to existing hospital outpatient departments, which has allowed higher Medicare payments. In a press release, Braun estimated that their proposed site-neutral change could save taxpayers $40 billion over a decade.
As Debate Continues, States Are Moving Ahead With Changes
Consumer activists have won a few battles this year at the state level about facility fees.
In July, Maine Gov. Janet Mills, a Democrat, signed a law that requires medical organizations to report facility fees to the state, which will share them publicly. Facility fees can pop up after a patient has received an insurance company estimate of the out-of-pocket costs for care.
“Patients receive bills bloated by healthcare providers that overcharge for services and insurance companies that deny claims without explanation,” the Portland Press Herald reported in a 2022 story. “And with little clout to fight back or even negotiate, feeling helpless, they often give up and pay, worn down by a system that is as time-consuming as it is obtuse.”
In May, Colorado enacted a law that will require patient notification about facility fees at many hospitals in the state.
In June, Connecticut expanded its law regarding facility fees and prohibited them for certain routine outpatient healthcare services. A statement from Gov. Ned Lamont’s office said the original intent of these facility fees was to ensure hospitals could maintain the around-the-clock care needed for inpatient and emergency care.
“However, these fees have been increasingly applied to services such as diagnostic testing and other routine services,” the statement said.
But there have been setbacks as well for those seeking to curb facilities.
The Texas Hospital Association (THA) in May said its advocacy defeated a pair of state bills, House bill 1692 and Senate bill 1275, that sought to limit facility fees for outpatient services.
In rallying opposition to these bills, THA said the loss of facility fees would threaten care for patients. Facility fees help cover costs “beyond the doctor’s bill,” such as “lab technicians, interpreters, medical records, security personnel, janitorial staff, and others,” THA said.
More Patients Shopping?
It’s unclear when — or if — Congress and other states will take major steps to reduce additional payments to hospitals for outpatient care.
But the increased use of high deductibles in health plans is driving more consumers to try to understand all of the costs of medical procedures ahead of time and, thus, drawing attention to facility fees, said Charlie Byrge, the chief operating officer of MDsave.
The average annual deductible levels for an individual increased by 3.0% to $2004 from 2020 to 2021 and for a family plan by 3.9% to $3868, according to a federal report. Some people have higher deductibles, exceeding $5000, Mr. Byrge said.
“That’s creating an opportunity for firms that can connect physicians directly with patients who will pay part or all of the costs of a treatment out of pocket,” he told this news organization.
Doctors and hospitals work with MDsave to charge preset prices for certain services, such as colonoscopies and mammograms. Consumers then can shop online to see if they can save. For example, in Nashville, Tennessee, where MDsave is based, the cost of a colonoscopy through MDsave is $2334, about half of the $4714 national average, according to the firm’s website.
This model for pricing routine medical care is akin to those used for other products and services, where companies decide ahead of time what to charge, he said.
“You don’t buy an airline ticket from Southwest or United or Delta and then there’s a bill after the fact because the price of gas went up a little bit on your flight,” Mr. Byrge said.
This will drive more competition among hospitals and clinics, in places where there are several sites of care in a region, Mr. Byrge said. But there are advantages for physicians and hospitals from the MDsave approach, he said.
“They know they’re getting paid upfront. They’re not going through the delays and headaches of the insurance reimbursement process. There are no denials. It’s just an upfront payment, and I think that’s what we’re starting to see the market really moving toward,” he said.
A version of this article appeared on Medscape.com.
Can the US healthcare system learn something about how to operate from car dealerships? Lawrence Kosinski, MD, MBA, a governing board member of American Gastroenterological Association (AGA), believes so.
There’s growing concern in the United States about the lack of clarity surrounding facility fees, which are intended to cover costs of maintaining medical facilities. Dr. Kosinski thinks that Congress should look into the transparency mandate it created for car prices as a model for how to address this.
A 1958 federal law set the stage for the consumer-friendly breakdown of costs and relevant performance data that anyone who has bought a new vehicle in the United States would recognize.
“You look at that and you know exactly what you are paying for,” Dr. Kosinski told this news organization. “In healthcare, we need something like that.”
Novel solutions like Dr. Kosinski’s will be increasingly necessary, as lawmakers on the state and federal level have begun to set their sights on tackling this issue.
The Biden administration in July expressed concern about an increased use of facility fees for healthcare provided at doctors’ offices, saying these additional costs often surprise consumers. House Energy and Commerce Chairwoman Cathy McMorris Rodgers (R-WA) also raised this issue several times this year, including at a May meeting about pending legislation on price transparency for health services, where she mentioned the case of a man who underwent eye surgery in Maine.
“His bill included three separate facility fees totaling $7800 and professional fees totaling $6200,” Ms. Rodgers said. “Why are three facility fees necessary for 1 hour of surgery in one O.R.?”
AGA’s Dr. Kosinski said facility fees cover the additional costs hospitals and clinics face in providing even routine treatments for some patients. For example, colonoscopy for a patient with a body mass index of 50 would pose special challenges for the anesthesiologist.
These factors need to be considered in setting policies on facility fees, he said. But there is no reason hospitals and other sites of medical care can’t make the information about facility fees easy for patients to find and understand, Dr. Kosinski said.
“I’m struggling to see a reason why we can’t be more transparent,” he said.
Big Battles Ahead
There are two connected battles ahead regarding facility fees: Efforts to restrict these additional charges for many medical services and fights over the need for greater transparency in general about health costs.
Senate Health, Education, Labor and Pensions Chairman Bernie Sanders (I-VT) is seeking to broadly restrict facility fees through his pending Primary Care and Health Workforce Act (S. 2840). The measure would block hospitals from charging health plans facility fees for many evaluation, management, and telehealth services.
The American Hospital Association (AHA) opposes it. They argue that the current payment approach rightly accounts for the added costs incurred when hospitals treat patients who are more likely to be ill or have chronic conditions than those seen in independent practices.
AHA said hospitals also need to maintain standby capacity for natural and man-made disasters, public health emergencies, and unexpected traumatic events. In September, AHA launched a television ad campaign to oppose any drive toward site-neutral policies. AHA says reducing the extra payments could cause more hospitals to shut their doors.
But there’s persistent interest in site-neutral payment, the term describing when the same reimbursement is given for care regardless of setting. This would lower pay for hospitals.
Among those pressing for change is an umbrella group of medical organizations known as the Alliance for Site Neutral Payment Reform. Its members include the American Academy of Family Physicians, American Academy of Orthopaedic Surgeons, American College of Physicians, Community Oncology Alliance, and Digestive Health Physicians Association.
And on November 9, Sen. Maggie Hassan (D-NH) argued for eventually including a site-neutral Medicare provision to a major healthcare package that the Senate Finance Committee is putting together.
Sen. Hassan is seeking to end what she called the “the practice of charging patients unfair hospital facility fees for care provided in the off-campus outpatient setting, like at a regular doctor’s office.”
Senate Finance Chairman Ron Wyden (D-OR) and the ranking Republican on the committee, Sen. Mike Crapo (R-ID), told Sen. Hassan they intended to work with her to see if this issue could be addressed in the pending legislative package.
A 2015 budget deal marked the last time Congress took a major step to address the higher cost of services provided in hospital-owned facilities.
Lawmakers then were scrambling to find cuts to offset spending in what became the 2015 Bipartisan Budget Act. This law established site-neutral payments under Medicare for services received at off-campus outpatient departments but exempted hospitals that already ran these kinds of operations or had advanced plans to create them.
Lawmakers are well aware of the potential savings from site-neutral policies and could look in time again to use them as part of a future budget deal.
In fact, in June, Sen. Hassan and Sens. Mike Braun (R-IN) and John Kennedy (R-LA) introduced a bill meant to basically end the exemption given in the 2015 deal to existing hospital outpatient departments, which has allowed higher Medicare payments. In a press release, Braun estimated that their proposed site-neutral change could save taxpayers $40 billion over a decade.
As Debate Continues, States Are Moving Ahead With Changes
Consumer activists have won a few battles this year at the state level about facility fees.
In July, Maine Gov. Janet Mills, a Democrat, signed a law that requires medical organizations to report facility fees to the state, which will share them publicly. Facility fees can pop up after a patient has received an insurance company estimate of the out-of-pocket costs for care.
“Patients receive bills bloated by healthcare providers that overcharge for services and insurance companies that deny claims without explanation,” the Portland Press Herald reported in a 2022 story. “And with little clout to fight back or even negotiate, feeling helpless, they often give up and pay, worn down by a system that is as time-consuming as it is obtuse.”
In May, Colorado enacted a law that will require patient notification about facility fees at many hospitals in the state.
In June, Connecticut expanded its law regarding facility fees and prohibited them for certain routine outpatient healthcare services. A statement from Gov. Ned Lamont’s office said the original intent of these facility fees was to ensure hospitals could maintain the around-the-clock care needed for inpatient and emergency care.
“However, these fees have been increasingly applied to services such as diagnostic testing and other routine services,” the statement said.
But there have been setbacks as well for those seeking to curb facilities.
The Texas Hospital Association (THA) in May said its advocacy defeated a pair of state bills, House bill 1692 and Senate bill 1275, that sought to limit facility fees for outpatient services.
In rallying opposition to these bills, THA said the loss of facility fees would threaten care for patients. Facility fees help cover costs “beyond the doctor’s bill,” such as “lab technicians, interpreters, medical records, security personnel, janitorial staff, and others,” THA said.
More Patients Shopping?
It’s unclear when — or if — Congress and other states will take major steps to reduce additional payments to hospitals for outpatient care.
But the increased use of high deductibles in health plans is driving more consumers to try to understand all of the costs of medical procedures ahead of time and, thus, drawing attention to facility fees, said Charlie Byrge, the chief operating officer of MDsave.
The average annual deductible levels for an individual increased by 3.0% to $2004 from 2020 to 2021 and for a family plan by 3.9% to $3868, according to a federal report. Some people have higher deductibles, exceeding $5000, Mr. Byrge said.
“That’s creating an opportunity for firms that can connect physicians directly with patients who will pay part or all of the costs of a treatment out of pocket,” he told this news organization.
Doctors and hospitals work with MDsave to charge preset prices for certain services, such as colonoscopies and mammograms. Consumers then can shop online to see if they can save. For example, in Nashville, Tennessee, where MDsave is based, the cost of a colonoscopy through MDsave is $2334, about half of the $4714 national average, according to the firm’s website.
This model for pricing routine medical care is akin to those used for other products and services, where companies decide ahead of time what to charge, he said.
“You don’t buy an airline ticket from Southwest or United or Delta and then there’s a bill after the fact because the price of gas went up a little bit on your flight,” Mr. Byrge said.
This will drive more competition among hospitals and clinics, in places where there are several sites of care in a region, Mr. Byrge said. But there are advantages for physicians and hospitals from the MDsave approach, he said.
“They know they’re getting paid upfront. They’re not going through the delays and headaches of the insurance reimbursement process. There are no denials. It’s just an upfront payment, and I think that’s what we’re starting to see the market really moving toward,” he said.
A version of this article appeared on Medscape.com.
Can the US healthcare system learn something about how to operate from car dealerships? Lawrence Kosinski, MD, MBA, a governing board member of American Gastroenterological Association (AGA), believes so.
There’s growing concern in the United States about the lack of clarity surrounding facility fees, which are intended to cover costs of maintaining medical facilities. Dr. Kosinski thinks that Congress should look into the transparency mandate it created for car prices as a model for how to address this.
A 1958 federal law set the stage for the consumer-friendly breakdown of costs and relevant performance data that anyone who has bought a new vehicle in the United States would recognize.
“You look at that and you know exactly what you are paying for,” Dr. Kosinski told this news organization. “In healthcare, we need something like that.”
Novel solutions like Dr. Kosinski’s will be increasingly necessary, as lawmakers on the state and federal level have begun to set their sights on tackling this issue.
The Biden administration in July expressed concern about an increased use of facility fees for healthcare provided at doctors’ offices, saying these additional costs often surprise consumers. House Energy and Commerce Chairwoman Cathy McMorris Rodgers (R-WA) also raised this issue several times this year, including at a May meeting about pending legislation on price transparency for health services, where she mentioned the case of a man who underwent eye surgery in Maine.
“His bill included three separate facility fees totaling $7800 and professional fees totaling $6200,” Ms. Rodgers said. “Why are three facility fees necessary for 1 hour of surgery in one O.R.?”
AGA’s Dr. Kosinski said facility fees cover the additional costs hospitals and clinics face in providing even routine treatments for some patients. For example, colonoscopy for a patient with a body mass index of 50 would pose special challenges for the anesthesiologist.
These factors need to be considered in setting policies on facility fees, he said. But there is no reason hospitals and other sites of medical care can’t make the information about facility fees easy for patients to find and understand, Dr. Kosinski said.
“I’m struggling to see a reason why we can’t be more transparent,” he said.
Big Battles Ahead
There are two connected battles ahead regarding facility fees: Efforts to restrict these additional charges for many medical services and fights over the need for greater transparency in general about health costs.
Senate Health, Education, Labor and Pensions Chairman Bernie Sanders (I-VT) is seeking to broadly restrict facility fees through his pending Primary Care and Health Workforce Act (S. 2840). The measure would block hospitals from charging health plans facility fees for many evaluation, management, and telehealth services.
The American Hospital Association (AHA) opposes it. They argue that the current payment approach rightly accounts for the added costs incurred when hospitals treat patients who are more likely to be ill or have chronic conditions than those seen in independent practices.
AHA said hospitals also need to maintain standby capacity for natural and man-made disasters, public health emergencies, and unexpected traumatic events. In September, AHA launched a television ad campaign to oppose any drive toward site-neutral policies. AHA says reducing the extra payments could cause more hospitals to shut their doors.
But there’s persistent interest in site-neutral payment, the term describing when the same reimbursement is given for care regardless of setting. This would lower pay for hospitals.
Among those pressing for change is an umbrella group of medical organizations known as the Alliance for Site Neutral Payment Reform. Its members include the American Academy of Family Physicians, American Academy of Orthopaedic Surgeons, American College of Physicians, Community Oncology Alliance, and Digestive Health Physicians Association.
And on November 9, Sen. Maggie Hassan (D-NH) argued for eventually including a site-neutral Medicare provision to a major healthcare package that the Senate Finance Committee is putting together.
Sen. Hassan is seeking to end what she called the “the practice of charging patients unfair hospital facility fees for care provided in the off-campus outpatient setting, like at a regular doctor’s office.”
Senate Finance Chairman Ron Wyden (D-OR) and the ranking Republican on the committee, Sen. Mike Crapo (R-ID), told Sen. Hassan they intended to work with her to see if this issue could be addressed in the pending legislative package.
A 2015 budget deal marked the last time Congress took a major step to address the higher cost of services provided in hospital-owned facilities.
Lawmakers then were scrambling to find cuts to offset spending in what became the 2015 Bipartisan Budget Act. This law established site-neutral payments under Medicare for services received at off-campus outpatient departments but exempted hospitals that already ran these kinds of operations or had advanced plans to create them.
Lawmakers are well aware of the potential savings from site-neutral policies and could look in time again to use them as part of a future budget deal.
In fact, in June, Sen. Hassan and Sens. Mike Braun (R-IN) and John Kennedy (R-LA) introduced a bill meant to basically end the exemption given in the 2015 deal to existing hospital outpatient departments, which has allowed higher Medicare payments. In a press release, Braun estimated that their proposed site-neutral change could save taxpayers $40 billion over a decade.
As Debate Continues, States Are Moving Ahead With Changes
Consumer activists have won a few battles this year at the state level about facility fees.
In July, Maine Gov. Janet Mills, a Democrat, signed a law that requires medical organizations to report facility fees to the state, which will share them publicly. Facility fees can pop up after a patient has received an insurance company estimate of the out-of-pocket costs for care.
“Patients receive bills bloated by healthcare providers that overcharge for services and insurance companies that deny claims without explanation,” the Portland Press Herald reported in a 2022 story. “And with little clout to fight back or even negotiate, feeling helpless, they often give up and pay, worn down by a system that is as time-consuming as it is obtuse.”
In May, Colorado enacted a law that will require patient notification about facility fees at many hospitals in the state.
In June, Connecticut expanded its law regarding facility fees and prohibited them for certain routine outpatient healthcare services. A statement from Gov. Ned Lamont’s office said the original intent of these facility fees was to ensure hospitals could maintain the around-the-clock care needed for inpatient and emergency care.
“However, these fees have been increasingly applied to services such as diagnostic testing and other routine services,” the statement said.
But there have been setbacks as well for those seeking to curb facilities.
The Texas Hospital Association (THA) in May said its advocacy defeated a pair of state bills, House bill 1692 and Senate bill 1275, that sought to limit facility fees for outpatient services.
In rallying opposition to these bills, THA said the loss of facility fees would threaten care for patients. Facility fees help cover costs “beyond the doctor’s bill,” such as “lab technicians, interpreters, medical records, security personnel, janitorial staff, and others,” THA said.
More Patients Shopping?
It’s unclear when — or if — Congress and other states will take major steps to reduce additional payments to hospitals for outpatient care.
But the increased use of high deductibles in health plans is driving more consumers to try to understand all of the costs of medical procedures ahead of time and, thus, drawing attention to facility fees, said Charlie Byrge, the chief operating officer of MDsave.
The average annual deductible levels for an individual increased by 3.0% to $2004 from 2020 to 2021 and for a family plan by 3.9% to $3868, according to a federal report. Some people have higher deductibles, exceeding $5000, Mr. Byrge said.
“That’s creating an opportunity for firms that can connect physicians directly with patients who will pay part or all of the costs of a treatment out of pocket,” he told this news organization.
Doctors and hospitals work with MDsave to charge preset prices for certain services, such as colonoscopies and mammograms. Consumers then can shop online to see if they can save. For example, in Nashville, Tennessee, where MDsave is based, the cost of a colonoscopy through MDsave is $2334, about half of the $4714 national average, according to the firm’s website.
This model for pricing routine medical care is akin to those used for other products and services, where companies decide ahead of time what to charge, he said.
“You don’t buy an airline ticket from Southwest or United or Delta and then there’s a bill after the fact because the price of gas went up a little bit on your flight,” Mr. Byrge said.
This will drive more competition among hospitals and clinics, in places where there are several sites of care in a region, Mr. Byrge said. But there are advantages for physicians and hospitals from the MDsave approach, he said.
“They know they’re getting paid upfront. They’re not going through the delays and headaches of the insurance reimbursement process. There are no denials. It’s just an upfront payment, and I think that’s what we’re starting to see the market really moving toward,” he said.
A version of this article appeared on Medscape.com.
Tax Questions Frequently Asked by Physicians
Physicians spend years of their lives in education and training. There are countless hours devoted to studying, researching, and clinical training, not to mention residency and possible fellowships. Then literally overnight, they transition out of a resident salary into a full-time attending pay with little to no education around what to do with this significant increase in salary.
Every job position is unique in terms of benefits, how compensation is earned, job expectations, etc. But they all share one thing in common — taxes. Increased income comes with increased taxes. 
FAQ 1. What is the difference between W2 income and 1099 income?
A: If you are a W2 employee, your employer is responsible for paying half of your Social Security and Medicare taxes. You, as the employee, are then responsible only for the remaining half of your Social Security and Medicare taxes. Additionally, your employer will withhold these taxes, along with federal income taxes, from your paycheck each pay period. You are not responsible for remitting any taxes to the IRS or state agencies, as your employer will do this for you. As a W2 employee, you are not able to deduct any employee expenses against your income.
As a 1099 contractor, you are considered self-employed and are responsible for the employer and employee portion of the Social Security and Medicare taxes. You are also responsible for remitting these taxes, as well as quarterly estimated federal withholding, to the IRS and state agencies. You can deduct work-related expenses against your 1099 income.
Both types of income have pros and cons. Either of these can be more beneficial to a specific situation.
FAQ 2. How do I know if I am withholding enough taxes?
A: This is a very common issue I see, especially with physicians who are transitioning out of training into their full-time attending salary. Because this transition happens mid-year, often the first half of the year you are withholding at a rate much lower than what you will be earning as an attending and end up with a tax surprise at filing. One way to remedy this is to look at how much taxes are being withheld from your paycheck and compare this to what tax bracket you anticipate to be in, depending on filing status (Figure 1). If you do this and realize you are not withholding enough taxes, you can submit an amended form W4 to your employer to have additional withholding taken out each pay period.
FAQ 3. I am a 1099 contractor; do I need a PLLC, and should I file as an S-Corporation?
A: The term “S-Corp” gets mentioned often related to 1099 contractors and can be extremely beneficial from a tax savings perspective. Often physicians may moonlight — in addition to working in their W2 positions — and would receive this compensation as a 1099 contractor rather than an employee. This is an example of when a Professional Limited Liability Company (PLLC) might be advisable. A PLLC is created at a state level and helps shield owners from potential litigation. The owner of a PLLC pays Social Security and Medicare taxes on all income earned from the entity, and the PLLC is included in the owner’s individual income tax return.
A Small-Corporation (S-Corporation) is a tax classification that passes income through to the owners. The PLLC is now taxed as an S-Corporation, rather than a disregarded entity. The shareholders of the S-Corporation are required to pay a reasonable salary (W2 income). The remaining income passes through to the owner and is not subject to Social Security and Medicare taxes, only federal income tax. This taxation status requires an additional tax return and payroll service. Because there are additional expenses with being taxed as an S-Corporation, a cost-benefit analysis should be done before changing the tax classification to confirm that the tax savings are greater than the additional costs.
FAQ 4. What is the ‘backdoor Roth’ strategy? Should I implement it?
A: A Roth IRA is a specific type of Individual Retirement Account (IRA) that is funded with after-tax dollars. The contributions and growth in a Roth IRA can be withdrawn at retirement, tax free. As physicians who are typically high earners, you are not able to contribute directly to a Roth IRA because of income limitations. This is where the Roth conversion strategy — the backdoor Roth — comes into play. This strategy allows you to make a nondeductible traditional IRA contribution and then convert those dollars into a Roth IRA. In 2023, you can contribute up to $6,500 into this type of account. There are many additional considerations that must be made before implementing this strategy. Discussion with a financial advisor or CPA is recommended.
FAQ 5. I’ve always done my own taxes. Do I need to hire a CPA?
A: For many physicians, especially during training, your tax situation may not warrant the need for a Certified Public Accountant (CPA). However, as your income and tax complexity increase, working with a CPA not only decreases your risk for error, but also helps ensure you are not overpaying in taxes. There are many different types of services that a CPA can offer, the most basic being tax preparation. This is simply compiling your tax return based on the circumstances that occurred in the prior year. Tax planning is an additional level of service that may not be included in tax preparation cost. Tax planning is a proactive approach to taxes and helps maximize tax savings opportunities before return preparation. When interviewing a potential CPA, you can ask what level of services are included in the fees quoted.
These are just a few of the questions I regularly answer related to physicians’ taxation. The tax code is complex and ever changing. Recommendations that are made today might not be applicable or advisable in the future to any given situation. Working with a professional can ensure you have the most up-to-date and accurate information related to your taxes.
Ms. Anderson is with Physician’s Resource Services and is on Instagram @physiciansrs . Dr. Anderson is a CA-1 Resident in Anesthesia at Baylor Scott and White Health. The authors have no conflicts of interest.
Physicians spend years of their lives in education and training. There are countless hours devoted to studying, researching, and clinical training, not to mention residency and possible fellowships. Then literally overnight, they transition out of a resident salary into a full-time attending pay with little to no education around what to do with this significant increase in salary.
Every job position is unique in terms of benefits, how compensation is earned, job expectations, etc. But they all share one thing in common — taxes. Increased income comes with increased taxes.
FAQ 1. What is the difference between W2 income and 1099 income?
A: If you are a W2 employee, your employer is responsible for paying half of your Social Security and Medicare taxes. You, as the employee, are then responsible only for the remaining half of your Social Security and Medicare taxes. Additionally, your employer will withhold these taxes, along with federal income taxes, from your paycheck each pay period. You are not responsible for remitting any taxes to the IRS or state agencies, as your employer will do this for you. As a W2 employee, you are not able to deduct any employee expenses against your income.
As a 1099 contractor, you are considered self-employed and are responsible for the employer and employee portion of the Social Security and Medicare taxes. You are also responsible for remitting these taxes, as well as quarterly estimated federal withholding, to the IRS and state agencies. You can deduct work-related expenses against your 1099 income.
Both types of income have pros and cons. Either of these can be more beneficial to a specific situation.
FAQ 2. How do I know if I am withholding enough taxes?
A: This is a very common issue I see, especially with physicians who are transitioning out of training into their full-time attending salary. Because this transition happens mid-year, often the first half of the year you are withholding at a rate much lower than what you will be earning as an attending and end up with a tax surprise at filing. One way to remedy this is to look at how much taxes are being withheld from your paycheck and compare this to what tax bracket you anticipate to be in, depending on filing status (Figure 1). If you do this and realize you are not withholding enough taxes, you can submit an amended form W4 to your employer to have additional withholding taken out each pay period.
FAQ 3. I am a 1099 contractor; do I need a PLLC, and should I file as an S-Corporation?
A: The term “S-Corp” gets mentioned often related to 1099 contractors and can be extremely beneficial from a tax savings perspective. Often physicians may moonlight — in addition to working in their W2 positions — and would receive this compensation as a 1099 contractor rather than an employee. This is an example of when a Professional Limited Liability Company (PLLC) might be advisable. A PLLC is created at a state level and helps shield owners from potential litigation. The owner of a PLLC pays Social Security and Medicare taxes on all income earned from the entity, and the PLLC is included in the owner’s individual income tax return.
A Small-Corporation (S-Corporation) is a tax classification that passes income through to the owners. The PLLC is now taxed as an S-Corporation, rather than a disregarded entity. The shareholders of the S-Corporation are required to pay a reasonable salary (W2 income). The remaining income passes through to the owner and is not subject to Social Security and Medicare taxes, only federal income tax. This taxation status requires an additional tax return and payroll service. Because there are additional expenses with being taxed as an S-Corporation, a cost-benefit analysis should be done before changing the tax classification to confirm that the tax savings are greater than the additional costs.
FAQ 4. What is the ‘backdoor Roth’ strategy? Should I implement it?
A: A Roth IRA is a specific type of Individual Retirement Account (IRA) that is funded with after-tax dollars. The contributions and growth in a Roth IRA can be withdrawn at retirement, tax free. As physicians who are typically high earners, you are not able to contribute directly to a Roth IRA because of income limitations. This is where the Roth conversion strategy — the backdoor Roth — comes into play. This strategy allows you to make a nondeductible traditional IRA contribution and then convert those dollars into a Roth IRA. In 2023, you can contribute up to $6,500 into this type of account. There are many additional considerations that must be made before implementing this strategy. Discussion with a financial advisor or CPA is recommended.
FAQ 5. I’ve always done my own taxes. Do I need to hire a CPA?
A: For many physicians, especially during training, your tax situation may not warrant the need for a Certified Public Accountant (CPA). However, as your income and tax complexity increase, working with a CPA not only decreases your risk for error, but also helps ensure you are not overpaying in taxes. There are many different types of services that a CPA can offer, the most basic being tax preparation. This is simply compiling your tax return based on the circumstances that occurred in the prior year. Tax planning is an additional level of service that may not be included in tax preparation cost. Tax planning is a proactive approach to taxes and helps maximize tax savings opportunities before return preparation. When interviewing a potential CPA, you can ask what level of services are included in the fees quoted.
These are just a few of the questions I regularly answer related to physicians’ taxation. The tax code is complex and ever changing. Recommendations that are made today might not be applicable or advisable in the future to any given situation. Working with a professional can ensure you have the most up-to-date and accurate information related to your taxes.
Ms. Anderson is with Physician’s Resource Services and is on Instagram @physiciansrs . Dr. Anderson is a CA-1 Resident in Anesthesia at Baylor Scott and White Health. The authors have no conflicts of interest.
Physicians spend years of their lives in education and training. There are countless hours devoted to studying, researching, and clinical training, not to mention residency and possible fellowships. Then literally overnight, they transition out of a resident salary into a full-time attending pay with little to no education around what to do with this significant increase in salary.
Every job position is unique in terms of benefits, how compensation is earned, job expectations, etc. But they all share one thing in common — taxes. Increased income comes with increased taxes.
FAQ 1. What is the difference between W2 income and 1099 income?
A: If you are a W2 employee, your employer is responsible for paying half of your Social Security and Medicare taxes. You, as the employee, are then responsible only for the remaining half of your Social Security and Medicare taxes. Additionally, your employer will withhold these taxes, along with federal income taxes, from your paycheck each pay period. You are not responsible for remitting any taxes to the IRS or state agencies, as your employer will do this for you. As a W2 employee, you are not able to deduct any employee expenses against your income.
As a 1099 contractor, you are considered self-employed and are responsible for the employer and employee portion of the Social Security and Medicare taxes. You are also responsible for remitting these taxes, as well as quarterly estimated federal withholding, to the IRS and state agencies. You can deduct work-related expenses against your 1099 income.
Both types of income have pros and cons. Either of these can be more beneficial to a specific situation.
FAQ 2. How do I know if I am withholding enough taxes?
A: This is a very common issue I see, especially with physicians who are transitioning out of training into their full-time attending salary. Because this transition happens mid-year, often the first half of the year you are withholding at a rate much lower than what you will be earning as an attending and end up with a tax surprise at filing. One way to remedy this is to look at how much taxes are being withheld from your paycheck and compare this to what tax bracket you anticipate to be in, depending on filing status (Figure 1). If you do this and realize you are not withholding enough taxes, you can submit an amended form W4 to your employer to have additional withholding taken out each pay period.
FAQ 3. I am a 1099 contractor; do I need a PLLC, and should I file as an S-Corporation?
A: The term “S-Corp” gets mentioned often related to 1099 contractors and can be extremely beneficial from a tax savings perspective. Often physicians may moonlight — in addition to working in their W2 positions — and would receive this compensation as a 1099 contractor rather than an employee. This is an example of when a Professional Limited Liability Company (PLLC) might be advisable. A PLLC is created at a state level and helps shield owners from potential litigation. The owner of a PLLC pays Social Security and Medicare taxes on all income earned from the entity, and the PLLC is included in the owner’s individual income tax return.
A Small-Corporation (S-Corporation) is a tax classification that passes income through to the owners. The PLLC is now taxed as an S-Corporation, rather than a disregarded entity. The shareholders of the S-Corporation are required to pay a reasonable salary (W2 income). The remaining income passes through to the owner and is not subject to Social Security and Medicare taxes, only federal income tax. This taxation status requires an additional tax return and payroll service. Because there are additional expenses with being taxed as an S-Corporation, a cost-benefit analysis should be done before changing the tax classification to confirm that the tax savings are greater than the additional costs.
FAQ 4. What is the ‘backdoor Roth’ strategy? Should I implement it?
A: A Roth IRA is a specific type of Individual Retirement Account (IRA) that is funded with after-tax dollars. The contributions and growth in a Roth IRA can be withdrawn at retirement, tax free. As physicians who are typically high earners, you are not able to contribute directly to a Roth IRA because of income limitations. This is where the Roth conversion strategy — the backdoor Roth — comes into play. This strategy allows you to make a nondeductible traditional IRA contribution and then convert those dollars into a Roth IRA. In 2023, you can contribute up to $6,500 into this type of account. There are many additional considerations that must be made before implementing this strategy. Discussion with a financial advisor or CPA is recommended.
FAQ 5. I’ve always done my own taxes. Do I need to hire a CPA?
A: For many physicians, especially during training, your tax situation may not warrant the need for a Certified Public Accountant (CPA). However, as your income and tax complexity increase, working with a CPA not only decreases your risk for error, but also helps ensure you are not overpaying in taxes. There are many different types of services that a CPA can offer, the most basic being tax preparation. This is simply compiling your tax return based on the circumstances that occurred in the prior year. Tax planning is an additional level of service that may not be included in tax preparation cost. Tax planning is a proactive approach to taxes and helps maximize tax savings opportunities before return preparation. When interviewing a potential CPA, you can ask what level of services are included in the fees quoted.
These are just a few of the questions I regularly answer related to physicians’ taxation. The tax code is complex and ever changing. Recommendations that are made today might not be applicable or advisable in the future to any given situation. Working with a professional can ensure you have the most up-to-date and accurate information related to your taxes.
Ms. Anderson is with Physician’s Resource Services and is on Instagram @physiciansrs . Dr. Anderson is a CA-1 Resident in Anesthesia at Baylor Scott and White Health. The authors have no conflicts of interest.
Roflumilast foam gets nod as new option for seborrheic dermatitis
The in a press release.
The 0.3% foam, marketed as Zoryve, applied once-daily, is indicated for patients aged 9 years and older with seborrheic dermatitis, and can be used anywhere on the body, including areas with hair, with no limits on duration of use, according to the company, Arcutis. A 0.3% cream formulation of roflumilast was previously approved by the FDA for the topical treatment of plaque psoriasis in patients aged 6 years and older.
Approval was based on data from the phase 3 STRATUM trial and an accompanying phase 2 study known as Trial 203. These studies included a total of 683 adults and youth aged 9 years and older with seborrheic dermatitis. Participants were randomized to roflumilast or a placebo.
At 8 weeks, 79.5 % of patients on roflumilast met the primary efficacy endpoint of Investigator Global Assessment (IGA) scores of 0 or 1 (clear or almost clear) compared with 58.0% of patients on placebo (P < .001); the results were similar in the phase 2 Trial 203 (73.1% vs. 40.8%, respectively; P < .001). Overall, more than 50% of the patients on roflumilast achieved a clear score.
Patients in the roflumilast group also showed significant improvement in all secondary endpoints, including itching, scaling, and erythema, according to the company.
In the STRATUM study, 62.8% of roflumilast-treated patients and 40.6% of placebo patients achieved a 4-point or more reduction in itch based on the Worst Itch Numerical Rating Score (P =.0001), and 28% of roflumilast-treated patients reported significant itch improvement within the first 48 hours of use, compared with 13% of placebo patients (P = .0024).
Over a treatment period of up to 1 year, no treatment-related severe adverse events were reported in the phase 2 and 3 studies. The incidence of treatment emergent adverse events was similar between the treatment and placebo groups, and the most common adverse events (occurring in 1% of more of patients) across both studies were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
Roflumilast foam is scheduled to be available by the end of January 2024, according to the company. The product is for topical use only, and contraindicated for individuals with severe liver impairment.
The in a press release.
The 0.3% foam, marketed as Zoryve, applied once-daily, is indicated for patients aged 9 years and older with seborrheic dermatitis, and can be used anywhere on the body, including areas with hair, with no limits on duration of use, according to the company, Arcutis. A 0.3% cream formulation of roflumilast was previously approved by the FDA for the topical treatment of plaque psoriasis in patients aged 6 years and older.
Approval was based on data from the phase 3 STRATUM trial and an accompanying phase 2 study known as Trial 203. These studies included a total of 683 adults and youth aged 9 years and older with seborrheic dermatitis. Participants were randomized to roflumilast or a placebo.
At 8 weeks, 79.5 % of patients on roflumilast met the primary efficacy endpoint of Investigator Global Assessment (IGA) scores of 0 or 1 (clear or almost clear) compared with 58.0% of patients on placebo (P < .001); the results were similar in the phase 2 Trial 203 (73.1% vs. 40.8%, respectively; P < .001). Overall, more than 50% of the patients on roflumilast achieved a clear score.
Patients in the roflumilast group also showed significant improvement in all secondary endpoints, including itching, scaling, and erythema, according to the company.
In the STRATUM study, 62.8% of roflumilast-treated patients and 40.6% of placebo patients achieved a 4-point or more reduction in itch based on the Worst Itch Numerical Rating Score (P =.0001), and 28% of roflumilast-treated patients reported significant itch improvement within the first 48 hours of use, compared with 13% of placebo patients (P = .0024).
Over a treatment period of up to 1 year, no treatment-related severe adverse events were reported in the phase 2 and 3 studies. The incidence of treatment emergent adverse events was similar between the treatment and placebo groups, and the most common adverse events (occurring in 1% of more of patients) across both studies were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
Roflumilast foam is scheduled to be available by the end of January 2024, according to the company. The product is for topical use only, and contraindicated for individuals with severe liver impairment.
The in a press release.
The 0.3% foam, marketed as Zoryve, applied once-daily, is indicated for patients aged 9 years and older with seborrheic dermatitis, and can be used anywhere on the body, including areas with hair, with no limits on duration of use, according to the company, Arcutis. A 0.3% cream formulation of roflumilast was previously approved by the FDA for the topical treatment of plaque psoriasis in patients aged 6 years and older.
Approval was based on data from the phase 3 STRATUM trial and an accompanying phase 2 study known as Trial 203. These studies included a total of 683 adults and youth aged 9 years and older with seborrheic dermatitis. Participants were randomized to roflumilast or a placebo.
At 8 weeks, 79.5 % of patients on roflumilast met the primary efficacy endpoint of Investigator Global Assessment (IGA) scores of 0 or 1 (clear or almost clear) compared with 58.0% of patients on placebo (P < .001); the results were similar in the phase 2 Trial 203 (73.1% vs. 40.8%, respectively; P < .001). Overall, more than 50% of the patients on roflumilast achieved a clear score.
Patients in the roflumilast group also showed significant improvement in all secondary endpoints, including itching, scaling, and erythema, according to the company.
In the STRATUM study, 62.8% of roflumilast-treated patients and 40.6% of placebo patients achieved a 4-point or more reduction in itch based on the Worst Itch Numerical Rating Score (P =.0001), and 28% of roflumilast-treated patients reported significant itch improvement within the first 48 hours of use, compared with 13% of placebo patients (P = .0024).
Over a treatment period of up to 1 year, no treatment-related severe adverse events were reported in the phase 2 and 3 studies. The incidence of treatment emergent adverse events was similar between the treatment and placebo groups, and the most common adverse events (occurring in 1% of more of patients) across both studies were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
Roflumilast foam is scheduled to be available by the end of January 2024, according to the company. The product is for topical use only, and contraindicated for individuals with severe liver impairment.
Survival-Toxicity Trade-off With T-DM1 in HER+ Breast Cancer
SAN ANTONIO — in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.
Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the “first-line treatment for HER2-positive advanced breast cancer, regardless of age,” said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium.
However, he noted that the standard-of-care regimen appears to be “intolerable mentally and physically” in those older than 65 years, and “impairs” quality of life.
Therefore a “new standard treatment with less toxicity and noninferior efficacy for older patients is needed,” said Dr. Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.
Dr. Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.
Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.
Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.
At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).
There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).
However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.
Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.
The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).
Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.
Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a “detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment,” said Shimomura.
Virginia Kaklamani, MD, codirector of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, said in an interview that the trial shows T-DM1 could be “a good alternative to our first line therapy in HER2+ metastatic breast cancer” for some patients.
“It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials,” she said.
The study was funded by the Japanese National Cancer Center. Dr. Shimomura declares relationships with Daiichi Sankyo, Pfizer, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD Co. Ltd, Eisai Co. Ltd, Gilead Sciences, and Taiho Pharmaceutical Co. Ltd.
A version of this article appeared on Medscape.com.
SAN ANTONIO — in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.
Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the “first-line treatment for HER2-positive advanced breast cancer, regardless of age,” said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium.
However, he noted that the standard-of-care regimen appears to be “intolerable mentally and physically” in those older than 65 years, and “impairs” quality of life.
Therefore a “new standard treatment with less toxicity and noninferior efficacy for older patients is needed,” said Dr. Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.
Dr. Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.
Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.
Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.
At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).
There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).
However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.
Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.
The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).
Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.
Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a “detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment,” said Shimomura.
Virginia Kaklamani, MD, codirector of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, said in an interview that the trial shows T-DM1 could be “a good alternative to our first line therapy in HER2+ metastatic breast cancer” for some patients.
“It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials,” she said.
The study was funded by the Japanese National Cancer Center. Dr. Shimomura declares relationships with Daiichi Sankyo, Pfizer, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD Co. Ltd, Eisai Co. Ltd, Gilead Sciences, and Taiho Pharmaceutical Co. Ltd.
A version of this article appeared on Medscape.com.
SAN ANTONIO — in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.
Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the “first-line treatment for HER2-positive advanced breast cancer, regardless of age,” said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium.
However, he noted that the standard-of-care regimen appears to be “intolerable mentally and physically” in those older than 65 years, and “impairs” quality of life.
Therefore a “new standard treatment with less toxicity and noninferior efficacy for older patients is needed,” said Dr. Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.
Dr. Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.
Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.
Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.
At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).
There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).
However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.
Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.
The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).
Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.
Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a “detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment,” said Shimomura.
Virginia Kaklamani, MD, codirector of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, said in an interview that the trial shows T-DM1 could be “a good alternative to our first line therapy in HER2+ metastatic breast cancer” for some patients.
“It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials,” she said.
The study was funded by the Japanese National Cancer Center. Dr. Shimomura declares relationships with Daiichi Sankyo, Pfizer, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD Co. Ltd, Eisai Co. Ltd, Gilead Sciences, and Taiho Pharmaceutical Co. Ltd.
A version of this article appeared on Medscape.com.
AT SABCS 2023