MDedge Dermatology

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Therapeutic patient education is an important, effective, and well-defined intervention for patients with atopic dermatitis (AD), Andreas Wollenberg, MD, said at the Revolutionizing Atopic Dermatitis symposium.

A major goal of patient education is increasing medication adherence, noted Dr. Wollenberg, professor in the department of dermatology and allergy at Ludwig Maximilian University of Munich. Quoting former U.S. Surgeon General C. Everett Koop, MD, he said, “drugs don’t work in patients who don’t take them.”

While this is a simple message, it is important, Dr. Wollenberg said, noting that there can be a gap between a physician’s well-intentioned message and how it is interpreted by the patient. “Our messages may not be heard, not understood, not accepted, and even if they are put into place, how long will they last?” he asked. “We need to find a way [to] place sticky messages in the brains of our patients who are sitting and interacting with us.”

One way to improve treatment adherence is through patient education, such as using a written action plan or graphics; simplifying treatment regimens; minimizing treatment costs; setting up reminder programs, early follow-up visits, and short-term treatment goals; and minimizing nocebo effects. “This is more than providing just leaflets to patients. It is a complete program. It is a holistic approach. It should be structured and should be interdisciplinary, and it should contain a psychological component,” Dr. Wollenberg said.

Therapeutic patient education is recommended at baseline for children and adults with moderate to severe AD in the 2020 European Task Force on Atopic Dermatitis (ETFAD) and European Academy of Dermatology and Venereology (EADV) position paper on the diagnosis and treatment of AD in adults and children, alongside other interventions, such as emollients, bath oils, and avoidance of clinically relevant allergens, noted Dr. Wollenberg, the first author . “Therapeutic patient education is an extremely helpful tool to address patient beliefs and questions regarding disease and treatment,” he and his coauthors wrote in the paper.

When considering a therapeutic patient education program for AD, content is key, but just as important is consideration of legal and cultural conditions in the local area, Dr. Wollenberg explained. Every country will need some degree of standardization of content, he noted. Clinicians interested in adopting a patient education program need to consider who will pay for it – patients, foundations, or insurance companies – as well as the time commitment needed.

Dr. Wollenberg said that his team uses an evidence-based education program for AD in Germany that works across patients with different personalities, with a multidisciplinary team that includes a dermatologist, a specialist nurse, a nutrition expert, and a psychologist. “Sometimes we replace the specialized nurse with the dermatology resident because, in Germany, it’s difficult to find any type of specialized nurse,” although this is not an issue in many other countries, he said.

The model for children involves six 90-minute sessions, which cover topics that include emollients and basic care, food allergies and diet, medical treatment, and psychology of itch. The program for adults involves six 2-hour sessions, which cover topics that include psychology, skin care/nutrition, and medical treatment.

While this education program improves adherence in patients with AD, he acknowledged it is time consuming, and may not work for people who live far away from a clinic or who have other time commitments, making an alternative format necessary.

In terms of improving patient adherence to a doctor’s recommendations regarding chronic skin disease, “we cannot change our patients, we cannot change the disease, but we can strongly influence the treatment that we choose and how we interact as physicians with our patients,” said Dr. Wollenberg.

“Therapeutic patient education is virtually free of side effects, but evidence based. Have a look [at] it and adapt it to your own practice,” he added.

Dr. Wollenberg is a consultant, speaker and receives fees from numerous pharmaceutical companies.

Therapeutic patient education is an important, effective, and well-defined intervention for patients with atopic dermatitis (AD), Andreas Wollenberg, MD, said at the Revolutionizing Atopic Dermatitis symposium.

A major goal of patient education is increasing medication adherence, noted Dr. Wollenberg, professor in the department of dermatology and allergy at Ludwig Maximilian University of Munich. Quoting former U.S. Surgeon General C. Everett Koop, MD, he said, “drugs don’t work in patients who don’t take them.”

While this is a simple message, it is important, Dr. Wollenberg said, noting that there can be a gap between a physician’s well-intentioned message and how it is interpreted by the patient. “Our messages may not be heard, not understood, not accepted, and even if they are put into place, how long will they last?” he asked. “We need to find a way [to] place sticky messages in the brains of our patients who are sitting and interacting with us.”

One way to improve treatment adherence is through patient education, such as using a written action plan or graphics; simplifying treatment regimens; minimizing treatment costs; setting up reminder programs, early follow-up visits, and short-term treatment goals; and minimizing nocebo effects. “This is more than providing just leaflets to patients. It is a complete program. It is a holistic approach. It should be structured and should be interdisciplinary, and it should contain a psychological component,” Dr. Wollenberg said.

Therapeutic patient education is recommended at baseline for children and adults with moderate to severe AD in the 2020 European Task Force on Atopic Dermatitis (ETFAD) and European Academy of Dermatology and Venereology (EADV) position paper on the diagnosis and treatment of AD in adults and children, alongside other interventions, such as emollients, bath oils, and avoidance of clinically relevant allergens, noted Dr. Wollenberg, the first author . “Therapeutic patient education is an extremely helpful tool to address patient beliefs and questions regarding disease and treatment,” he and his coauthors wrote in the paper.

When considering a therapeutic patient education program for AD, content is key, but just as important is consideration of legal and cultural conditions in the local area, Dr. Wollenberg explained. Every country will need some degree of standardization of content, he noted. Clinicians interested in adopting a patient education program need to consider who will pay for it – patients, foundations, or insurance companies – as well as the time commitment needed.

Dr. Wollenberg said that his team uses an evidence-based education program for AD in Germany that works across patients with different personalities, with a multidisciplinary team that includes a dermatologist, a specialist nurse, a nutrition expert, and a psychologist. “Sometimes we replace the specialized nurse with the dermatology resident because, in Germany, it’s difficult to find any type of specialized nurse,” although this is not an issue in many other countries, he said.

The model for children involves six 90-minute sessions, which cover topics that include emollients and basic care, food allergies and diet, medical treatment, and psychology of itch. The program for adults involves six 2-hour sessions, which cover topics that include psychology, skin care/nutrition, and medical treatment.

While this education program improves adherence in patients with AD, he acknowledged it is time consuming, and may not work for people who live far away from a clinic or who have other time commitments, making an alternative format necessary.

In terms of improving patient adherence to a doctor’s recommendations regarding chronic skin disease, “we cannot change our patients, we cannot change the disease, but we can strongly influence the treatment that we choose and how we interact as physicians with our patients,” said Dr. Wollenberg.

“Therapeutic patient education is virtually free of side effects, but evidence based. Have a look [at] it and adapt it to your own practice,” he added.

Dr. Wollenberg is a consultant, speaker and receives fees from numerous pharmaceutical companies.

Therapeutic patient education is an important, effective, and well-defined intervention for patients with atopic dermatitis (AD), Andreas Wollenberg, MD, said at the Revolutionizing Atopic Dermatitis symposium.

A major goal of patient education is increasing medication adherence, noted Dr. Wollenberg, professor in the department of dermatology and allergy at Ludwig Maximilian University of Munich. Quoting former U.S. Surgeon General C. Everett Koop, MD, he said, “drugs don’t work in patients who don’t take them.”

While this is a simple message, it is important, Dr. Wollenberg said, noting that there can be a gap between a physician’s well-intentioned message and how it is interpreted by the patient. “Our messages may not be heard, not understood, not accepted, and even if they are put into place, how long will they last?” he asked. “We need to find a way [to] place sticky messages in the brains of our patients who are sitting and interacting with us.”

One way to improve treatment adherence is through patient education, such as using a written action plan or graphics; simplifying treatment regimens; minimizing treatment costs; setting up reminder programs, early follow-up visits, and short-term treatment goals; and minimizing nocebo effects. “This is more than providing just leaflets to patients. It is a complete program. It is a holistic approach. It should be structured and should be interdisciplinary, and it should contain a psychological component,” Dr. Wollenberg said.

Therapeutic patient education is recommended at baseline for children and adults with moderate to severe AD in the 2020 European Task Force on Atopic Dermatitis (ETFAD) and European Academy of Dermatology and Venereology (EADV) position paper on the diagnosis and treatment of AD in adults and children, alongside other interventions, such as emollients, bath oils, and avoidance of clinically relevant allergens, noted Dr. Wollenberg, the first author . “Therapeutic patient education is an extremely helpful tool to address patient beliefs and questions regarding disease and treatment,” he and his coauthors wrote in the paper.

When considering a therapeutic patient education program for AD, content is key, but just as important is consideration of legal and cultural conditions in the local area, Dr. Wollenberg explained. Every country will need some degree of standardization of content, he noted. Clinicians interested in adopting a patient education program need to consider who will pay for it – patients, foundations, or insurance companies – as well as the time commitment needed.

Dr. Wollenberg said that his team uses an evidence-based education program for AD in Germany that works across patients with different personalities, with a multidisciplinary team that includes a dermatologist, a specialist nurse, a nutrition expert, and a psychologist. “Sometimes we replace the specialized nurse with the dermatology resident because, in Germany, it’s difficult to find any type of specialized nurse,” although this is not an issue in many other countries, he said.

The model for children involves six 90-minute sessions, which cover topics that include emollients and basic care, food allergies and diet, medical treatment, and psychology of itch. The program for adults involves six 2-hour sessions, which cover topics that include psychology, skin care/nutrition, and medical treatment.

While this education program improves adherence in patients with AD, he acknowledged it is time consuming, and may not work for people who live far away from a clinic or who have other time commitments, making an alternative format necessary.

In terms of improving patient adherence to a doctor’s recommendations regarding chronic skin disease, “we cannot change our patients, we cannot change the disease, but we can strongly influence the treatment that we choose and how we interact as physicians with our patients,” said Dr. Wollenberg.

“Therapeutic patient education is virtually free of side effects, but evidence based. Have a look [at] it and adapt it to your own practice,” he added.

Dr. Wollenberg is a consultant, speaker and receives fees from numerous pharmaceutical companies.

Living the dream, diagnosing the nightmare

Does a bad dream mean you should be consulting your doctor about an impending neurologic disease? Maybe.

New research published in eClinicalMedicine suggests that, for some people, bad dreams and nightmares have been associated with developing Parkinson’s disease later in life. Dr. Abidemi I. Otaiku of the University of Birmingham (England) analyzed data from a cohort study involving 3,818 older men, of whom 2.3% were diagnosed with Parkinson’s during the 12 years of follow-up.

©Wavebreakmedia Ltd/Thinkstock

Dr. Otaiku found those with frequent nightmares – at least once per week – were twice as likely to develop Parkinson’s than were those without, with most of the diagnoses coming in the first 5 years.

Although more research needs to be done, “identifying the significance of bad dreams and nightmares could indicate that individuals who experience changes to their dreams in older age – without any obvious trigger – should seek medical advice,” he said in a Eurekalert statement.

Dr. Otaiku pointed out that studying dreams can tell us a lot about how our brains work and are structured. By using electroencephalography, Dr. Otaiku plans to look into the biological reasons for why we dream the way we do.

So could it be that those killer clowns are actually giving you a heads up on your health?
 

Maybe next time try a paper route

There’s just no winning with teenagers sometimes. You tell them to go outside, they’ll sit in the dark playing video games all night. You tell them to get better grades, they’ll skip school. You tell them to get a hobby, they’ll scam the German government for millions of euros.

The COVID-19 pandemic has been tricky for governments to manage. Massive amounts of infrastructure needed to be set up, and that means corners got cut. Germany was no exception in this regard; the government entrusted the Kassenärztlichen Vereinigung, a doctor’s association, with overseeing COVID testing and payment at private test centers. To make things a bit easier, all they required private test centers to provide to receive reimbursement was an invoice.

AvailableLight/Getty Images

This is where our 17-year-old from Freiburg comes in. In a spark of entrepreneurial genius, he decided to falsify documents and create an entirely fictional COVID test center. The KV approved it, and between March and July of 2021, he sent in thousands of fake invoices. Over that 4-month period, he submitted 500,000 invoices and received 5.7 million euros as compensation. That’s a few thousand tests per day, which was absolutely absurd, but he avoided scrutiny for months.

In the end, it wasn’t even the KV that noticed the fraud, but the bank. A bank employee noticed millions flowing into the account of a teenager and suspected money laundering, alerting the government. Fortunately for our young friend, since he was under 18 when he hatched his scheme, he was tried as a minor, avoiding jail time. His ill-gotten gains were confiscated, he has to pay a relatively minimal fine, and he will be on probation for 1 year. And presumably, he’ll be on the receiving end of the grounding of a lifetime.
 

You look like I need more sleep

Like most people, not getting our beauty sleep can make us look tired and feel less attractive, but a new study from Sweden shows that the sleep deprived also are more likely to find others less attractive. That’s probably not a good finding for singles who often go out trying to meet someone after a long day of work.

PRImageFactory/iStock/Getty Images

For the study, 45 young men and women were required to spend one night with no sleep and then another night with the possibility of 8 hours of sleep. The following mornings, eye-tracking technology was used as they looked at images of happy, angry, fearful, and neutral faces. The subjects then rated the faces for attractiveness, trustworthiness, and healthiness.

“The finding that sleep-deprived subjects in our experiment rated angry faces as less trustworthy and healthy-looking and neutral and fearful faces as less attractive indicates that sleep loss is associated with more negative social impressions of others,” senior author Christian Benedict of Uppsala University said in a statement.

When we are sleep deprived, the researchers added, we might not stop to really look at someone else, which has a negative impact on how we perceive people because we are not focusing on what their facial expressions are really telling us.

We already knew that not sleeping well has many negative effects on us, but now – thank you very much, science – we have something else to think about. Better hope your crush at work gets enough sleep so you’ll be accurately noticed.
 

The expanding-hole illusion of science

Time for a LOTME-style reality check: I think, therefore I am.

So far, so good. Next step: I think, therefore I am. I think.

Works for us. Now for the biggie: I think I am seeing the black hole in the middle of this image expanding.

Laeng, Nabil, and Kitaoka

Does that work for you? Do you perceive the black hole as expanding? If you do, then you fit in with the 86% of subjects in a recent study who perceived the same thing.

Lead author Bruno Laeng of the University of Oslo explained the effect in a statement from Frontiers Science News. “The circular smear or shadow gradient of the central black hole evokes a marked impression of optic flow, as if the observer were heading forward into a hole or tunnel. ... The pupil reacts to how we perceive light – even if this ‘light’ is imaginary like in the illusion – and not just to the amount of light energy that actually enters the eye.”

The illusion is so good at deceiving the brain “that it even prompts a dilation reflex of the pupils to let in more light, just as would happen if we were really moving into a dark area,” the investigators said.

Of the 50 men and women who had their eye movements measured while looking at the illusion, only 14% didn’t perceive the illusion when the hole was black. When the hole was a color, that figure went up to 20%. There also was a strong dilation reflex with black holes, but colored holes caused the subjects’ pupils to constrict, they noted.

Dr. Laeng and his associates can’t explain why some people don’t see the movement, but they did offer this: “Pupils’ dilation or contraction reflex is not a closed-loop mechanism, like a photocell opening a door, impervious to any other information than the actual amount of light stimulating the photoreceptor. Rather, the eye adjusts to perceived and even imagined light, not simply to physical energy.”

And now, back to our reality check: We think we perceive the light of a cheeseburger, therefore it’s time for lunch.

Living the dream, diagnosing the nightmare

Does a bad dream mean you should be consulting your doctor about an impending neurologic disease? Maybe.

New research published in eClinicalMedicine suggests that, for some people, bad dreams and nightmares have been associated with developing Parkinson’s disease later in life. Dr. Abidemi I. Otaiku of the University of Birmingham (England) analyzed data from a cohort study involving 3,818 older men, of whom 2.3% were diagnosed with Parkinson’s during the 12 years of follow-up.

©Wavebreakmedia Ltd/Thinkstock

Dr. Otaiku found those with frequent nightmares – at least once per week – were twice as likely to develop Parkinson’s than were those without, with most of the diagnoses coming in the first 5 years.

Although more research needs to be done, “identifying the significance of bad dreams and nightmares could indicate that individuals who experience changes to their dreams in older age – without any obvious trigger – should seek medical advice,” he said in a Eurekalert statement.

Dr. Otaiku pointed out that studying dreams can tell us a lot about how our brains work and are structured. By using electroencephalography, Dr. Otaiku plans to look into the biological reasons for why we dream the way we do.

So could it be that those killer clowns are actually giving you a heads up on your health?
 

Maybe next time try a paper route

There’s just no winning with teenagers sometimes. You tell them to go outside, they’ll sit in the dark playing video games all night. You tell them to get better grades, they’ll skip school. You tell them to get a hobby, they’ll scam the German government for millions of euros.

The COVID-19 pandemic has been tricky for governments to manage. Massive amounts of infrastructure needed to be set up, and that means corners got cut. Germany was no exception in this regard; the government entrusted the Kassenärztlichen Vereinigung, a doctor’s association, with overseeing COVID testing and payment at private test centers. To make things a bit easier, all they required private test centers to provide to receive reimbursement was an invoice.

AvailableLight/Getty Images

This is where our 17-year-old from Freiburg comes in. In a spark of entrepreneurial genius, he decided to falsify documents and create an entirely fictional COVID test center. The KV approved it, and between March and July of 2021, he sent in thousands of fake invoices. Over that 4-month period, he submitted 500,000 invoices and received 5.7 million euros as compensation. That’s a few thousand tests per day, which was absolutely absurd, but he avoided scrutiny for months.

In the end, it wasn’t even the KV that noticed the fraud, but the bank. A bank employee noticed millions flowing into the account of a teenager and suspected money laundering, alerting the government. Fortunately for our young friend, since he was under 18 when he hatched his scheme, he was tried as a minor, avoiding jail time. His ill-gotten gains were confiscated, he has to pay a relatively minimal fine, and he will be on probation for 1 year. And presumably, he’ll be on the receiving end of the grounding of a lifetime.
 

You look like I need more sleep

Like most people, not getting our beauty sleep can make us look tired and feel less attractive, but a new study from Sweden shows that the sleep deprived also are more likely to find others less attractive. That’s probably not a good finding for singles who often go out trying to meet someone after a long day of work.

PRImageFactory/iStock/Getty Images

For the study, 45 young men and women were required to spend one night with no sleep and then another night with the possibility of 8 hours of sleep. The following mornings, eye-tracking technology was used as they looked at images of happy, angry, fearful, and neutral faces. The subjects then rated the faces for attractiveness, trustworthiness, and healthiness.

“The finding that sleep-deprived subjects in our experiment rated angry faces as less trustworthy and healthy-looking and neutral and fearful faces as less attractive indicates that sleep loss is associated with more negative social impressions of others,” senior author Christian Benedict of Uppsala University said in a statement.

When we are sleep deprived, the researchers added, we might not stop to really look at someone else, which has a negative impact on how we perceive people because we are not focusing on what their facial expressions are really telling us.

We already knew that not sleeping well has many negative effects on us, but now – thank you very much, science – we have something else to think about. Better hope your crush at work gets enough sleep so you’ll be accurately noticed.
 

The expanding-hole illusion of science

Time for a LOTME-style reality check: I think, therefore I am.

So far, so good. Next step: I think, therefore I am. I think.

Works for us. Now for the biggie: I think I am seeing the black hole in the middle of this image expanding.

Laeng, Nabil, and Kitaoka

Does that work for you? Do you perceive the black hole as expanding? If you do, then you fit in with the 86% of subjects in a recent study who perceived the same thing.

Lead author Bruno Laeng of the University of Oslo explained the effect in a statement from Frontiers Science News. “The circular smear or shadow gradient of the central black hole evokes a marked impression of optic flow, as if the observer were heading forward into a hole or tunnel. ... The pupil reacts to how we perceive light – even if this ‘light’ is imaginary like in the illusion – and not just to the amount of light energy that actually enters the eye.”

The illusion is so good at deceiving the brain “that it even prompts a dilation reflex of the pupils to let in more light, just as would happen if we were really moving into a dark area,” the investigators said.

Of the 50 men and women who had their eye movements measured while looking at the illusion, only 14% didn’t perceive the illusion when the hole was black. When the hole was a color, that figure went up to 20%. There also was a strong dilation reflex with black holes, but colored holes caused the subjects’ pupils to constrict, they noted.

Dr. Laeng and his associates can’t explain why some people don’t see the movement, but they did offer this: “Pupils’ dilation or contraction reflex is not a closed-loop mechanism, like a photocell opening a door, impervious to any other information than the actual amount of light stimulating the photoreceptor. Rather, the eye adjusts to perceived and even imagined light, not simply to physical energy.”

And now, back to our reality check: We think we perceive the light of a cheeseburger, therefore it’s time for lunch.

Living the dream, diagnosing the nightmare

Does a bad dream mean you should be consulting your doctor about an impending neurologic disease? Maybe.

New research published in eClinicalMedicine suggests that, for some people, bad dreams and nightmares have been associated with developing Parkinson’s disease later in life. Dr. Abidemi I. Otaiku of the University of Birmingham (England) analyzed data from a cohort study involving 3,818 older men, of whom 2.3% were diagnosed with Parkinson’s during the 12 years of follow-up.

©Wavebreakmedia Ltd/Thinkstock

Dr. Otaiku found those with frequent nightmares – at least once per week – were twice as likely to develop Parkinson’s than were those without, with most of the diagnoses coming in the first 5 years.

Although more research needs to be done, “identifying the significance of bad dreams and nightmares could indicate that individuals who experience changes to their dreams in older age – without any obvious trigger – should seek medical advice,” he said in a Eurekalert statement.

Dr. Otaiku pointed out that studying dreams can tell us a lot about how our brains work and are structured. By using electroencephalography, Dr. Otaiku plans to look into the biological reasons for why we dream the way we do.

So could it be that those killer clowns are actually giving you a heads up on your health?
 

Maybe next time try a paper route

There’s just no winning with teenagers sometimes. You tell them to go outside, they’ll sit in the dark playing video games all night. You tell them to get better grades, they’ll skip school. You tell them to get a hobby, they’ll scam the German government for millions of euros.

The COVID-19 pandemic has been tricky for governments to manage. Massive amounts of infrastructure needed to be set up, and that means corners got cut. Germany was no exception in this regard; the government entrusted the Kassenärztlichen Vereinigung, a doctor’s association, with overseeing COVID testing and payment at private test centers. To make things a bit easier, all they required private test centers to provide to receive reimbursement was an invoice.

AvailableLight/Getty Images

This is where our 17-year-old from Freiburg comes in. In a spark of entrepreneurial genius, he decided to falsify documents and create an entirely fictional COVID test center. The KV approved it, and between March and July of 2021, he sent in thousands of fake invoices. Over that 4-month period, he submitted 500,000 invoices and received 5.7 million euros as compensation. That’s a few thousand tests per day, which was absolutely absurd, but he avoided scrutiny for months.

In the end, it wasn’t even the KV that noticed the fraud, but the bank. A bank employee noticed millions flowing into the account of a teenager and suspected money laundering, alerting the government. Fortunately for our young friend, since he was under 18 when he hatched his scheme, he was tried as a minor, avoiding jail time. His ill-gotten gains were confiscated, he has to pay a relatively minimal fine, and he will be on probation for 1 year. And presumably, he’ll be on the receiving end of the grounding of a lifetime.
 

You look like I need more sleep

Like most people, not getting our beauty sleep can make us look tired and feel less attractive, but a new study from Sweden shows that the sleep deprived also are more likely to find others less attractive. That’s probably not a good finding for singles who often go out trying to meet someone after a long day of work.

PRImageFactory/iStock/Getty Images

For the study, 45 young men and women were required to spend one night with no sleep and then another night with the possibility of 8 hours of sleep. The following mornings, eye-tracking technology was used as they looked at images of happy, angry, fearful, and neutral faces. The subjects then rated the faces for attractiveness, trustworthiness, and healthiness.

“The finding that sleep-deprived subjects in our experiment rated angry faces as less trustworthy and healthy-looking and neutral and fearful faces as less attractive indicates that sleep loss is associated with more negative social impressions of others,” senior author Christian Benedict of Uppsala University said in a statement.

When we are sleep deprived, the researchers added, we might not stop to really look at someone else, which has a negative impact on how we perceive people because we are not focusing on what their facial expressions are really telling us.

We already knew that not sleeping well has many negative effects on us, but now – thank you very much, science – we have something else to think about. Better hope your crush at work gets enough sleep so you’ll be accurately noticed.
 

The expanding-hole illusion of science

Time for a LOTME-style reality check: I think, therefore I am.

So far, so good. Next step: I think, therefore I am. I think.

Works for us. Now for the biggie: I think I am seeing the black hole in the middle of this image expanding.

Laeng, Nabil, and Kitaoka

Does that work for you? Do you perceive the black hole as expanding? If you do, then you fit in with the 86% of subjects in a recent study who perceived the same thing.

Lead author Bruno Laeng of the University of Oslo explained the effect in a statement from Frontiers Science News. “The circular smear or shadow gradient of the central black hole evokes a marked impression of optic flow, as if the observer were heading forward into a hole or tunnel. ... The pupil reacts to how we perceive light – even if this ‘light’ is imaginary like in the illusion – and not just to the amount of light energy that actually enters the eye.”

The illusion is so good at deceiving the brain “that it even prompts a dilation reflex of the pupils to let in more light, just as would happen if we were really moving into a dark area,” the investigators said.

Of the 50 men and women who had their eye movements measured while looking at the illusion, only 14% didn’t perceive the illusion when the hole was black. When the hole was a color, that figure went up to 20%. There also was a strong dilation reflex with black holes, but colored holes caused the subjects’ pupils to constrict, they noted.

Dr. Laeng and his associates can’t explain why some people don’t see the movement, but they did offer this: “Pupils’ dilation or contraction reflex is not a closed-loop mechanism, like a photocell opening a door, impervious to any other information than the actual amount of light stimulating the photoreceptor. Rather, the eye adjusts to perceived and even imagined light, not simply to physical energy.”

And now, back to our reality check: We think we perceive the light of a cheeseburger, therefore it’s time for lunch.

SAN DIEGO – When Lacy M. Alexander, PhD, began her career as a kinesiology researcher, she focused on the skin as a model of circulation for examining mechanisms of vascular function and dysfunction in diseases, as well as the influence of drug interventions.

“The skin is an accessible circulation; we see many of the same neural and endothelial pathways mediating vasodilation that we see throughout the entire vascular system,” Dr. Alexander, professor of kinesiology at Penn State University’s College of Health and Human Development, University Park, Pa., said during a lecture at the annual meeting of the American College for Sports Medicine.

Doug Brunk/MDedge News

The main technique that she and other researchers use to examine microvascular endothelial function is intradermal microdialysis, which involves the placement of a thin catheter into the dermis. “This catheter has the ability to perfuse or infuse various substances into a bidirectional membrane,” Dr. Alexander explained. “This enables us to recover various substances into that catheter. We pair this with a measurement of skin blood flow with Doppler probes as well as the ability to control local temperature to either isolate reflex control of the human cutaneous circulation or elicit local changes in temperature to elicit vasodilation and vasoconstriction.”

In a 2005 article on evaluating the microcirculation in vascular disease, microvascular dysfunction is described as “a systemic disease process that occurs in a similar fashion in multiple tissue beds throughout the body”. Therefore, early identification of the mechanism leading to microvascular dysfunction is important, Dr. Alexander said. “We can also monitor the progression of disease and the progression of a given treatment if we have a noninvasive way to do that.”

A question that clinicians often ask Dr. Alexander is, do changes in forearm skin blood flow represent changes in, say, leg skin blood flow, or blood flow in other parts of the body? “The answer to that question is yes; we see similar changes in forearm skin that we see in other regions of the body,” she said. “We tend to use the forearm skin because there’s less UV damage, especially when we’re looking at questions related to human aging.”

Over the years, she and other investigators have used intradermal microdialysis to develop and refine many skin-specific approaches for examining endothelial function, including reactive hyperemia, direct drug delivery, local heating, whole body heating, local cooling, whole body cooling, and spectral analysis. For example, using this approach in the direct drug delivery realm, researchers have discovered that oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolemic middle-aged adults.

In more recent work using intradermal microdialysis, researchers have observed that peripheral microvascular function is impaired in adults with hypertension (Hypertension. 2017; 69[5]:902-9).

Another study using intradermal microdialysis found that 16 weeks of a sulfhydryl intervention improved endothelial function through nitric oxide and hydrogen sulfide-dependent mechanisms in adults with hypertension.

The technology has also helped to further understanding of nontraditional risk factors of microvascular dysfunction. In one study, researchers found that endothelium-dependent vasodilation is blunted in adults with major depressive disorder due to a reduced functional contribution of nitric oxide.

According to Dr. Alexander, a study being reviewed for publication found that microvascular endothelial function is impaired in women with endometriosis.

Also in 2019, a European Academy of Allergy and Clinical Immunology (EAACI) position paper on the use of intradermal microdialysis in investigations of the pathogenesis of chronic inflammatory skin diseases was published.

The broad focus of Dr. Alexander’s current projects includes examining the roles of arginase in nitric oxide synthase uncoupling in human vasculature with hypercholesterolemia and hypertension; inflammation-induced alteration in vasodilatory signaling with essential hypertension; the role of reactive oxygen species in altering vasoconstriction and vascular remodeling with hypertension, and the effects of common platelet inhibitors on microvascular function in human skin as they relate to basic mechanisms of skin blood flow and functional thermoregulatory outcomes. “The hope is that we can intervene with things like dietary and exercise interventions early on to mitigate this progression to avert cardiovascular disease,” she said.

Dr. Alexander disclosed that she has received research support from the National Heart, Lung, and Blood Institute, the National Dairy Council, the American College of Sports Medicine, and the American Heart Association.

SAN DIEGO – When Lacy M. Alexander, PhD, began her career as a kinesiology researcher, she focused on the skin as a model of circulation for examining mechanisms of vascular function and dysfunction in diseases, as well as the influence of drug interventions.

“The skin is an accessible circulation; we see many of the same neural and endothelial pathways mediating vasodilation that we see throughout the entire vascular system,” Dr. Alexander, professor of kinesiology at Penn State University’s College of Health and Human Development, University Park, Pa., said during a lecture at the annual meeting of the American College for Sports Medicine.

Doug Brunk/MDedge News

The main technique that she and other researchers use to examine microvascular endothelial function is intradermal microdialysis, which involves the placement of a thin catheter into the dermis. “This catheter has the ability to perfuse or infuse various substances into a bidirectional membrane,” Dr. Alexander explained. “This enables us to recover various substances into that catheter. We pair this with a measurement of skin blood flow with Doppler probes as well as the ability to control local temperature to either isolate reflex control of the human cutaneous circulation or elicit local changes in temperature to elicit vasodilation and vasoconstriction.”

In a 2005 article on evaluating the microcirculation in vascular disease, microvascular dysfunction is described as “a systemic disease process that occurs in a similar fashion in multiple tissue beds throughout the body”. Therefore, early identification of the mechanism leading to microvascular dysfunction is important, Dr. Alexander said. “We can also monitor the progression of disease and the progression of a given treatment if we have a noninvasive way to do that.”

A question that clinicians often ask Dr. Alexander is, do changes in forearm skin blood flow represent changes in, say, leg skin blood flow, or blood flow in other parts of the body? “The answer to that question is yes; we see similar changes in forearm skin that we see in other regions of the body,” she said. “We tend to use the forearm skin because there’s less UV damage, especially when we’re looking at questions related to human aging.”

Over the years, she and other investigators have used intradermal microdialysis to develop and refine many skin-specific approaches for examining endothelial function, including reactive hyperemia, direct drug delivery, local heating, whole body heating, local cooling, whole body cooling, and spectral analysis. For example, using this approach in the direct drug delivery realm, researchers have discovered that oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolemic middle-aged adults.

In more recent work using intradermal microdialysis, researchers have observed that peripheral microvascular function is impaired in adults with hypertension (Hypertension. 2017; 69[5]:902-9).

Another study using intradermal microdialysis found that 16 weeks of a sulfhydryl intervention improved endothelial function through nitric oxide and hydrogen sulfide-dependent mechanisms in adults with hypertension.

The technology has also helped to further understanding of nontraditional risk factors of microvascular dysfunction. In one study, researchers found that endothelium-dependent vasodilation is blunted in adults with major depressive disorder due to a reduced functional contribution of nitric oxide.

According to Dr. Alexander, a study being reviewed for publication found that microvascular endothelial function is impaired in women with endometriosis.

Also in 2019, a European Academy of Allergy and Clinical Immunology (EAACI) position paper on the use of intradermal microdialysis in investigations of the pathogenesis of chronic inflammatory skin diseases was published.

The broad focus of Dr. Alexander’s current projects includes examining the roles of arginase in nitric oxide synthase uncoupling in human vasculature with hypercholesterolemia and hypertension; inflammation-induced alteration in vasodilatory signaling with essential hypertension; the role of reactive oxygen species in altering vasoconstriction and vascular remodeling with hypertension, and the effects of common platelet inhibitors on microvascular function in human skin as they relate to basic mechanisms of skin blood flow and functional thermoregulatory outcomes. “The hope is that we can intervene with things like dietary and exercise interventions early on to mitigate this progression to avert cardiovascular disease,” she said.

Dr. Alexander disclosed that she has received research support from the National Heart, Lung, and Blood Institute, the National Dairy Council, the American College of Sports Medicine, and the American Heart Association.

SAN DIEGO – When Lacy M. Alexander, PhD, began her career as a kinesiology researcher, she focused on the skin as a model of circulation for examining mechanisms of vascular function and dysfunction in diseases, as well as the influence of drug interventions.

“The skin is an accessible circulation; we see many of the same neural and endothelial pathways mediating vasodilation that we see throughout the entire vascular system,” Dr. Alexander, professor of kinesiology at Penn State University’s College of Health and Human Development, University Park, Pa., said during a lecture at the annual meeting of the American College for Sports Medicine.

Doug Brunk/MDedge News

The main technique that she and other researchers use to examine microvascular endothelial function is intradermal microdialysis, which involves the placement of a thin catheter into the dermis. “This catheter has the ability to perfuse or infuse various substances into a bidirectional membrane,” Dr. Alexander explained. “This enables us to recover various substances into that catheter. We pair this with a measurement of skin blood flow with Doppler probes as well as the ability to control local temperature to either isolate reflex control of the human cutaneous circulation or elicit local changes in temperature to elicit vasodilation and vasoconstriction.”

In a 2005 article on evaluating the microcirculation in vascular disease, microvascular dysfunction is described as “a systemic disease process that occurs in a similar fashion in multiple tissue beds throughout the body”. Therefore, early identification of the mechanism leading to microvascular dysfunction is important, Dr. Alexander said. “We can also monitor the progression of disease and the progression of a given treatment if we have a noninvasive way to do that.”

A question that clinicians often ask Dr. Alexander is, do changes in forearm skin blood flow represent changes in, say, leg skin blood flow, or blood flow in other parts of the body? “The answer to that question is yes; we see similar changes in forearm skin that we see in other regions of the body,” she said. “We tend to use the forearm skin because there’s less UV damage, especially when we’re looking at questions related to human aging.”

Over the years, she and other investigators have used intradermal microdialysis to develop and refine many skin-specific approaches for examining endothelial function, including reactive hyperemia, direct drug delivery, local heating, whole body heating, local cooling, whole body cooling, and spectral analysis. For example, using this approach in the direct drug delivery realm, researchers have discovered that oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolemic middle-aged adults.

In more recent work using intradermal microdialysis, researchers have observed that peripheral microvascular function is impaired in adults with hypertension (Hypertension. 2017; 69[5]:902-9).

Another study using intradermal microdialysis found that 16 weeks of a sulfhydryl intervention improved endothelial function through nitric oxide and hydrogen sulfide-dependent mechanisms in adults with hypertension.

The technology has also helped to further understanding of nontraditional risk factors of microvascular dysfunction. In one study, researchers found that endothelium-dependent vasodilation is blunted in adults with major depressive disorder due to a reduced functional contribution of nitric oxide.

According to Dr. Alexander, a study being reviewed for publication found that microvascular endothelial function is impaired in women with endometriosis.

Also in 2019, a European Academy of Allergy and Clinical Immunology (EAACI) position paper on the use of intradermal microdialysis in investigations of the pathogenesis of chronic inflammatory skin diseases was published.

The broad focus of Dr. Alexander’s current projects includes examining the roles of arginase in nitric oxide synthase uncoupling in human vasculature with hypercholesterolemia and hypertension; inflammation-induced alteration in vasodilatory signaling with essential hypertension; the role of reactive oxygen species in altering vasoconstriction and vascular remodeling with hypertension, and the effects of common platelet inhibitors on microvascular function in human skin as they relate to basic mechanisms of skin blood flow and functional thermoregulatory outcomes. “The hope is that we can intervene with things like dietary and exercise interventions early on to mitigate this progression to avert cardiovascular disease,” she said.

Dr. Alexander disclosed that she has received research support from the National Heart, Lung, and Blood Institute, the National Dairy Council, the American College of Sports Medicine, and the American Heart Association.

As the use of biologics for dermatologic conditions has increased, so have questions from patients about their safety during pregnancy and lactation, their effects on fertility, and potential effects on the developing fetus and the child’s development.

“I get asked a lot about fertility,” Vivian Shi, MD, associate professor of dermatology at the University of Arkansas, Little Rock, said at MedscapeLive’s Women’s and Pediatric Dermatology Seminar. Patients want to know, she said, if they go on a specific drug, whether it will affect their chances of conceiving and what else they need to know about safety.

She told the audience what she tells her patients: The answers are not complete but are evolving at a steady pace.

“Putting this talk together was kind of like a scavenger hunt,” said Dr. Shi, who gathered data from pregnancy exposure registries, published research, the Food and Drug Administration, and other sources on biologics. As more studies emerge each year, she said, recommendations will become stronger for considering treatment by certain biological drugs, taking into account effects on fertility, pregnancy, lactation, and the infant.

Among the biologics commonly used in dermatology are:

• Tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab).
• Interleukin (IL)–12 and -23 antagonist (ustekinumab).
• IL-17 antagonists (ixekizumab, secukinumab, brodalumab).
• IL-23 antagonists (risankizumab, tildrakizumab, guselkumab).
• IL-4, -13 antagonist (dupilumab) and IL-13 antagonist (tralokinumab).
• CD20-directed cytolytic antibody (rituximab).

To help with decision-making, Dr. Shi discussed the relatively new FDA labeling regulations as well as pregnancy exposure registries, research studies, and recommendations.
 

FDA pregnancy risk summaries

Under the previous system of classification of drugs in pregnancy, the FDA rated drugs as A, B, C, D, X. These categories ranged from showing no risks to the fetus to clear risk, but were oversimplistic and confusing, Dr. Shi said. Category C was especially confusing, as a drug with no animal or human data was put in the same category as a drug with adverse fetal effects on animals, she noted.

However, effective June 30, 2015, the FDA replaced pregnancy categories with risk summaries by medication. As of June, 2020, all prescription drugs were to remove pregnancy letter labeling. The risk summaries note human data when they are available and also note when no data are available. This information, Dr. Shi said, originates from many sources, including studies published in the medical literature, postmarketing studies conducted by companies, and pregnancy exposure registries, conducted by some companies and others. The FDA does not endorse any specific registries, but does post a list of such registries. Another helpful resource, she said, is Mother to Baby, a service of the nonprofit Organization of Teratology Information Specialists (OTIS).



Known, not known

Citing published literature, Dr. Shi said that TNF inhibitors have the most robust safety data from preconception to after birth. Less is known, she said, about the reproductive safety effects of other biologics used for dermatologic conditions, as they are newer than the anti-TNF medicines.

She reviewed a variety of research studies evaluating the safety of biologics during pregnancy and beyond. Highlights include results from a large registry, the Psoriasis Longitudinal Assessment and Registry (PSOLAR), of 298 pregnancies in about 220 women from 2007 to 2019, looking at 13 different biologics. The overall and live-birth outcomes in the women on biologics for psoriasis were similar to those for the general population and the rate of congenital anomalies was 0.8%, researchers reported in 2021, lower than the generally cited annual figure of U.S. births.

Studies evaluating biologics for nondermatologic conditions suggest safety. A prospective cohort study of women who took adalimumab in pregnancy (for rheumatoid arthritis or Crohn’s disease) found no increased risk for birth defects. In another study looking at women who were breastfeeding, researchers found no increased risk of infections or delay in developmental milestones in the children of women taking biologics for inflammatory bowel disease, compared with those not on the medications.

A report using data from the World Health Organization concludes that dupilumab appears to be safe during pregnancy, based on an evaluation of 36 pregnancy-related reports among more than 37,000 unique adverse event reports related to dupilumab in a global database.

Recommendations about biologic use from different organizations don’t always mesh, Dr. Shi said, noting that European guidelines tend to be stricter, as some reviews show.

If a mother is exposed to any biologic therapy other than certolizumab during the third trimester, after 27 weeks, Dr. Shi said, “you want to consider avoiding a live vaccine for the first 6 months of the baby’s life.” It turns out, she said, the only recommended live vaccine during that period is the rotavirus vaccine, and she suggests doctors recommend postponing that one until the babies are older if women have been on biologics other than certolizumab.

Her other take-home messages: TNF inhibitors have the most robust safety data from before conception through lactation. Under current guidelines, certolizumab is viewed as the safest to use throughout pregnancy. Dr. Shi’s message to her colleagues fielding the same questions she gets from patients: “There is more data coming out every year. Ultimately, we will have better information to inform our patients.”

At the conference, Lawrence F. Eichenfield, MD, a course director and professor of dermatology and pediatrics at the University of California, San Diego and Rady Children’s Hospital San Diego, encouraged Dr. Shi to write up her presentation as a resource for other dermatologists – which she said is in progress.

Medscape Live and this news organization are owned by the same parent company. Dr. Shi disclosed consulting and investigative and research funding from several pharmaceutical firms, but not directly related to the content of her presentation.

As the use of biologics for dermatologic conditions has increased, so have questions from patients about their safety during pregnancy and lactation, their effects on fertility, and potential effects on the developing fetus and the child’s development.

“I get asked a lot about fertility,” Vivian Shi, MD, associate professor of dermatology at the University of Arkansas, Little Rock, said at MedscapeLive’s Women’s and Pediatric Dermatology Seminar. Patients want to know, she said, if they go on a specific drug, whether it will affect their chances of conceiving and what else they need to know about safety.

She told the audience what she tells her patients: The answers are not complete but are evolving at a steady pace.

“Putting this talk together was kind of like a scavenger hunt,” said Dr. Shi, who gathered data from pregnancy exposure registries, published research, the Food and Drug Administration, and other sources on biologics. As more studies emerge each year, she said, recommendations will become stronger for considering treatment by certain biological drugs, taking into account effects on fertility, pregnancy, lactation, and the infant.

Among the biologics commonly used in dermatology are:

• Tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab).
• Interleukin (IL)–12 and -23 antagonist (ustekinumab).
• IL-17 antagonists (ixekizumab, secukinumab, brodalumab).
• IL-23 antagonists (risankizumab, tildrakizumab, guselkumab).
• IL-4, -13 antagonist (dupilumab) and IL-13 antagonist (tralokinumab).
• CD20-directed cytolytic antibody (rituximab).

To help with decision-making, Dr. Shi discussed the relatively new FDA labeling regulations as well as pregnancy exposure registries, research studies, and recommendations.
 

FDA pregnancy risk summaries

Under the previous system of classification of drugs in pregnancy, the FDA rated drugs as A, B, C, D, X. These categories ranged from showing no risks to the fetus to clear risk, but were oversimplistic and confusing, Dr. Shi said. Category C was especially confusing, as a drug with no animal or human data was put in the same category as a drug with adverse fetal effects on animals, she noted.

However, effective June 30, 2015, the FDA replaced pregnancy categories with risk summaries by medication. As of June, 2020, all prescription drugs were to remove pregnancy letter labeling. The risk summaries note human data when they are available and also note when no data are available. This information, Dr. Shi said, originates from many sources, including studies published in the medical literature, postmarketing studies conducted by companies, and pregnancy exposure registries, conducted by some companies and others. The FDA does not endorse any specific registries, but does post a list of such registries. Another helpful resource, she said, is Mother to Baby, a service of the nonprofit Organization of Teratology Information Specialists (OTIS).



Known, not known

Citing published literature, Dr. Shi said that TNF inhibitors have the most robust safety data from preconception to after birth. Less is known, she said, about the reproductive safety effects of other biologics used for dermatologic conditions, as they are newer than the anti-TNF medicines.

She reviewed a variety of research studies evaluating the safety of biologics during pregnancy and beyond. Highlights include results from a large registry, the Psoriasis Longitudinal Assessment and Registry (PSOLAR), of 298 pregnancies in about 220 women from 2007 to 2019, looking at 13 different biologics. The overall and live-birth outcomes in the women on biologics for psoriasis were similar to those for the general population and the rate of congenital anomalies was 0.8%, researchers reported in 2021, lower than the generally cited annual figure of U.S. births.

Studies evaluating biologics for nondermatologic conditions suggest safety. A prospective cohort study of women who took adalimumab in pregnancy (for rheumatoid arthritis or Crohn’s disease) found no increased risk for birth defects. In another study looking at women who were breastfeeding, researchers found no increased risk of infections or delay in developmental milestones in the children of women taking biologics for inflammatory bowel disease, compared with those not on the medications.

A report using data from the World Health Organization concludes that dupilumab appears to be safe during pregnancy, based on an evaluation of 36 pregnancy-related reports among more than 37,000 unique adverse event reports related to dupilumab in a global database.

Recommendations about biologic use from different organizations don’t always mesh, Dr. Shi said, noting that European guidelines tend to be stricter, as some reviews show.

If a mother is exposed to any biologic therapy other than certolizumab during the third trimester, after 27 weeks, Dr. Shi said, “you want to consider avoiding a live vaccine for the first 6 months of the baby’s life.” It turns out, she said, the only recommended live vaccine during that period is the rotavirus vaccine, and she suggests doctors recommend postponing that one until the babies are older if women have been on biologics other than certolizumab.

Her other take-home messages: TNF inhibitors have the most robust safety data from before conception through lactation. Under current guidelines, certolizumab is viewed as the safest to use throughout pregnancy. Dr. Shi’s message to her colleagues fielding the same questions she gets from patients: “There is more data coming out every year. Ultimately, we will have better information to inform our patients.”

At the conference, Lawrence F. Eichenfield, MD, a course director and professor of dermatology and pediatrics at the University of California, San Diego and Rady Children’s Hospital San Diego, encouraged Dr. Shi to write up her presentation as a resource for other dermatologists – which she said is in progress.

Medscape Live and this news organization are owned by the same parent company. Dr. Shi disclosed consulting and investigative and research funding from several pharmaceutical firms, but not directly related to the content of her presentation.

As the use of biologics for dermatologic conditions has increased, so have questions from patients about their safety during pregnancy and lactation, their effects on fertility, and potential effects on the developing fetus and the child’s development.

“I get asked a lot about fertility,” Vivian Shi, MD, associate professor of dermatology at the University of Arkansas, Little Rock, said at MedscapeLive’s Women’s and Pediatric Dermatology Seminar. Patients want to know, she said, if they go on a specific drug, whether it will affect their chances of conceiving and what else they need to know about safety.

She told the audience what she tells her patients: The answers are not complete but are evolving at a steady pace.

“Putting this talk together was kind of like a scavenger hunt,” said Dr. Shi, who gathered data from pregnancy exposure registries, published research, the Food and Drug Administration, and other sources on biologics. As more studies emerge each year, she said, recommendations will become stronger for considering treatment by certain biological drugs, taking into account effects on fertility, pregnancy, lactation, and the infant.

Among the biologics commonly used in dermatology are:

• Tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab).
• Interleukin (IL)–12 and -23 antagonist (ustekinumab).
• IL-17 antagonists (ixekizumab, secukinumab, brodalumab).
• IL-23 antagonists (risankizumab, tildrakizumab, guselkumab).
• IL-4, -13 antagonist (dupilumab) and IL-13 antagonist (tralokinumab).
• CD20-directed cytolytic antibody (rituximab).

To help with decision-making, Dr. Shi discussed the relatively new FDA labeling regulations as well as pregnancy exposure registries, research studies, and recommendations.
 

FDA pregnancy risk summaries

Under the previous system of classification of drugs in pregnancy, the FDA rated drugs as A, B, C, D, X. These categories ranged from showing no risks to the fetus to clear risk, but were oversimplistic and confusing, Dr. Shi said. Category C was especially confusing, as a drug with no animal or human data was put in the same category as a drug with adverse fetal effects on animals, she noted.

However, effective June 30, 2015, the FDA replaced pregnancy categories with risk summaries by medication. As of June, 2020, all prescription drugs were to remove pregnancy letter labeling. The risk summaries note human data when they are available and also note when no data are available. This information, Dr. Shi said, originates from many sources, including studies published in the medical literature, postmarketing studies conducted by companies, and pregnancy exposure registries, conducted by some companies and others. The FDA does not endorse any specific registries, but does post a list of such registries. Another helpful resource, she said, is Mother to Baby, a service of the nonprofit Organization of Teratology Information Specialists (OTIS).



Known, not known

Citing published literature, Dr. Shi said that TNF inhibitors have the most robust safety data from preconception to after birth. Less is known, she said, about the reproductive safety effects of other biologics used for dermatologic conditions, as they are newer than the anti-TNF medicines.

She reviewed a variety of research studies evaluating the safety of biologics during pregnancy and beyond. Highlights include results from a large registry, the Psoriasis Longitudinal Assessment and Registry (PSOLAR), of 298 pregnancies in about 220 women from 2007 to 2019, looking at 13 different biologics. The overall and live-birth outcomes in the women on biologics for psoriasis were similar to those for the general population and the rate of congenital anomalies was 0.8%, researchers reported in 2021, lower than the generally cited annual figure of U.S. births.

Studies evaluating biologics for nondermatologic conditions suggest safety. A prospective cohort study of women who took adalimumab in pregnancy (for rheumatoid arthritis or Crohn’s disease) found no increased risk for birth defects. In another study looking at women who were breastfeeding, researchers found no increased risk of infections or delay in developmental milestones in the children of women taking biologics for inflammatory bowel disease, compared with those not on the medications.

A report using data from the World Health Organization concludes that dupilumab appears to be safe during pregnancy, based on an evaluation of 36 pregnancy-related reports among more than 37,000 unique adverse event reports related to dupilumab in a global database.

Recommendations about biologic use from different organizations don’t always mesh, Dr. Shi said, noting that European guidelines tend to be stricter, as some reviews show.

If a mother is exposed to any biologic therapy other than certolizumab during the third trimester, after 27 weeks, Dr. Shi said, “you want to consider avoiding a live vaccine for the first 6 months of the baby’s life.” It turns out, she said, the only recommended live vaccine during that period is the rotavirus vaccine, and she suggests doctors recommend postponing that one until the babies are older if women have been on biologics other than certolizumab.

Her other take-home messages: TNF inhibitors have the most robust safety data from before conception through lactation. Under current guidelines, certolizumab is viewed as the safest to use throughout pregnancy. Dr. Shi’s message to her colleagues fielding the same questions she gets from patients: “There is more data coming out every year. Ultimately, we will have better information to inform our patients.”

At the conference, Lawrence F. Eichenfield, MD, a course director and professor of dermatology and pediatrics at the University of California, San Diego and Rady Children’s Hospital San Diego, encouraged Dr. Shi to write up her presentation as a resource for other dermatologists – which she said is in progress.

Medscape Live and this news organization are owned by the same parent company. Dr. Shi disclosed consulting and investigative and research funding from several pharmaceutical firms, but not directly related to the content of her presentation.

The Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The approval, announced on June 7, 2022, makes dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, the first biologic available in the United States to treat uncontrolled moderate to severe atopic dermatitis in this age group. In this age group, it is administered subcutaneously every 4 weeks. Dupilumab remains the only biologic treatment approved for patients aged 6 years and older for this indication.

Approval was based on data from a 16-week pivotal phase 3 trial that evaluated the efficacy and safety of dupilumab added to standard of care topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis. The trial’s principal investigator, Amy S. Paller, MD, professor and chair of dermatology at Northwestern University, Chicago, and colleagues, found that, at 16 weeks, 28% of patients who were treated with dupilumab, added to low-potency TCS, met the primary endpoint of clear or almost clear skin, compared with 4% of those who received low-potency TCS alone (P < .0001).

In addition, patients who received the combined treatment experienced a 70% average improvement in disease severity from baseline, compared with a 20% improvement among those in the TCS-only group (P < .0001). They also experienced a 49% improvement in itch, compared with a 2% improvement among their counterparts in the TCS-only group (P < .0001).

Outside of the United States, the study’s coprimary endpoint was achievement of 75% or greater improvement in overall disease severity. More than half of the patients who received combined treatment (53%) met this endpoint, compared with 11% in the TCS-only group (P < .0001), according to the company.

Safety results were generally consistent with the safety profile of dupilumab in atopic dermatitis for patients aged 6 years and older. The most common adverse events that were more commonly observed with dupilumab included conjunctivitis (5% vs 0% in the placebo group) and herpes viral infections (6% vs. 5% in the placebo group). Among those on dupilumab, ages 6 months to 5 years, hand,foot, and mouth disease was reported in 5% and skin papilloma were reported in 2%, but these cases did not lead to discontinuation of treatment, according to the company release.

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

The Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The approval, announced on June 7, 2022, makes dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, the first biologic available in the United States to treat uncontrolled moderate to severe atopic dermatitis in this age group. In this age group, it is administered subcutaneously every 4 weeks. Dupilumab remains the only biologic treatment approved for patients aged 6 years and older for this indication.

Approval was based on data from a 16-week pivotal phase 3 trial that evaluated the efficacy and safety of dupilumab added to standard of care topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis. The trial’s principal investigator, Amy S. Paller, MD, professor and chair of dermatology at Northwestern University, Chicago, and colleagues, found that, at 16 weeks, 28% of patients who were treated with dupilumab, added to low-potency TCS, met the primary endpoint of clear or almost clear skin, compared with 4% of those who received low-potency TCS alone (P < .0001).

In addition, patients who received the combined treatment experienced a 70% average improvement in disease severity from baseline, compared with a 20% improvement among those in the TCS-only group (P < .0001). They also experienced a 49% improvement in itch, compared with a 2% improvement among their counterparts in the TCS-only group (P < .0001).

Outside of the United States, the study’s coprimary endpoint was achievement of 75% or greater improvement in overall disease severity. More than half of the patients who received combined treatment (53%) met this endpoint, compared with 11% in the TCS-only group (P < .0001), according to the company.

Safety results were generally consistent with the safety profile of dupilumab in atopic dermatitis for patients aged 6 years and older. The most common adverse events that were more commonly observed with dupilumab included conjunctivitis (5% vs 0% in the placebo group) and herpes viral infections (6% vs. 5% in the placebo group). Among those on dupilumab, ages 6 months to 5 years, hand,foot, and mouth disease was reported in 5% and skin papilloma were reported in 2%, but these cases did not lead to discontinuation of treatment, according to the company release.

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

The Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The approval, announced on June 7, 2022, makes dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, the first biologic available in the United States to treat uncontrolled moderate to severe atopic dermatitis in this age group. In this age group, it is administered subcutaneously every 4 weeks. Dupilumab remains the only biologic treatment approved for patients aged 6 years and older for this indication.

Approval was based on data from a 16-week pivotal phase 3 trial that evaluated the efficacy and safety of dupilumab added to standard of care topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis. The trial’s principal investigator, Amy S. Paller, MD, professor and chair of dermatology at Northwestern University, Chicago, and colleagues, found that, at 16 weeks, 28% of patients who were treated with dupilumab, added to low-potency TCS, met the primary endpoint of clear or almost clear skin, compared with 4% of those who received low-potency TCS alone (P < .0001).

In addition, patients who received the combined treatment experienced a 70% average improvement in disease severity from baseline, compared with a 20% improvement among those in the TCS-only group (P < .0001). They also experienced a 49% improvement in itch, compared with a 2% improvement among their counterparts in the TCS-only group (P < .0001).

Outside of the United States, the study’s coprimary endpoint was achievement of 75% or greater improvement in overall disease severity. More than half of the patients who received combined treatment (53%) met this endpoint, compared with 11% in the TCS-only group (P < .0001), according to the company.

Safety results were generally consistent with the safety profile of dupilumab in atopic dermatitis for patients aged 6 years and older. The most common adverse events that were more commonly observed with dupilumab included conjunctivitis (5% vs 0% in the placebo group) and herpes viral infections (6% vs. 5% in the placebo group). Among those on dupilumab, ages 6 months to 5 years, hand,foot, and mouth disease was reported in 5% and skin papilloma were reported in 2%, but these cases did not lead to discontinuation of treatment, according to the company release.

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

Actions taken against a physician’s license for substance use are more common than those for psychological impairment or actions related to physical health, according to a recent report. Despite a sharp uptick in 2011, substance use–specific license actions taken against physicians dropped in frequency between 2004 and 2020.

More than three fourths (76.3%) of license actions taken against physicians were related to substance use, according to a recent study published in JAMA. Psychological impairment was the reason associated with more than 1 in 10 (11.5%) actions taken against physicians’ licenses, while physical impairment was the reason behind approximately 12% of such actions, per the study.

Researchers analyzed 5032 actions taken against the licenses of U.S. physicians. The actions were reported to the National Practitioner Data Bank and were related to substance use, psychological impairment, and physical impairment. The National Practitioner Data Bank is a web-based repository of reports with information on medical malpractice payments and certain adverse actions related to healthcare practitioners, providers, and suppliers. It is provided by the Department of Health & Human Services.

“While there has been increased attention [on] the mental health of physicians, we wanted to understand the extent to which changes in attitudes and practices were reflected in actions taken by hospitals or licensing boards, which are reported in the National Practitioner Data Bank,” Lisa Rotenstein, MD, a primary care physician at Boston’s Brigham and Women’s Hospital and lead author of the study, told this news organization.

Dr. Rotenstein, who is an assistant professor at Harvard Medical School, Boston, studies issues of mental health among physicians and trainees. Dr. Rotenstein was the lead author of a 2016 study that found that more than a quarter (27.2%) of medical students have depressive symptoms. She was also lead author of a 2018 study published in JAMA on the prevalence of burnout among attending physicians.
 

Actions against physicians trending downward

2011 marked the peak in actions taken against physicians’ licenses for substance use, per the study, but actions related to substance use have otherwise maintained a steady decline over the past 17 years. Researchers found that physicians with license actions as a result of substance use or psychological impairment were more likely to receive indefinite penalties, while also having emergency action taken against their license to practice.

In addition, physicians who had actions taken against their licenses because of substance use or psychological impairment were more likely to accrue a greater number of actions over the course of their careers, according to the study.

About 47% of physicians reported experiencing burnout per Medscape’s Physician Burnout and Depression Report 2022: Stress, Anxiety, and Anger report. Burnout among emergency physicians spiked from 43% in 2020 to 60% in 2021, according to the report.

More than one quarter (26%) of physicians reported drinking alcohol to cope with burnout in 2020, according to Medscape’s 2021 Physician Burnout and Suicide Report. Per the 2021 report, 48% of physicians chose exercise to deal with burnout, while 35% indulged in eating junk food.

Peter Grinspoon, MD, a Boston-based primary care physician, wrote in The Los Angeles Times in 2016 that the rate of substance abuse among physicians starts at 10% and can go as high as 15%; by comparison, rates of substance use among the general population are 8%-10%. “What appears to account for the difference is physician distress, and in the case of drug abuse, plentiful access,” he added.

Dr. Grinspoon wrote a 2016 book called “Free Refills: A Doctor Confronts His Addiction,” which chronicles his experience in recovery and relapse as a physician who was dependent on opioid painkillers.

The findings from the recent study in JAMA “suggest we have made some progress in addressing issues related to substance use in ways that don’t result in license actions or even in meeting physicians’ need for support related to substance use,” said Dr. Rotenstein.

Still, she insists that there’s “substantial opportunity to improve mental health and support offerings for physicians and to reduce stigma related to seeking and receiving mental health support, ideally averting the need for license actions.”

According to Dr. Rotenstein, the cases listed in the National Practitioner Data Bank represent the most severe cases; these reports have risen to a high level of attention or concern and are the result of adverse action reports submitted by healthcare institutions and state licensing boards.

“There are many, many more physicians whose cases are not represented here but who struggle with depression, anxiety, substance use, and more,” said Dr. Rotenstein.

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

Actions taken against a physician’s license for substance use are more common than those for psychological impairment or actions related to physical health, according to a recent report. Despite a sharp uptick in 2011, substance use–specific license actions taken against physicians dropped in frequency between 2004 and 2020.

More than three fourths (76.3%) of license actions taken against physicians were related to substance use, according to a recent study published in JAMA. Psychological impairment was the reason associated with more than 1 in 10 (11.5%) actions taken against physicians’ licenses, while physical impairment was the reason behind approximately 12% of such actions, per the study.

Researchers analyzed 5032 actions taken against the licenses of U.S. physicians. The actions were reported to the National Practitioner Data Bank and were related to substance use, psychological impairment, and physical impairment. The National Practitioner Data Bank is a web-based repository of reports with information on medical malpractice payments and certain adverse actions related to healthcare practitioners, providers, and suppliers. It is provided by the Department of Health & Human Services.

“While there has been increased attention [on] the mental health of physicians, we wanted to understand the extent to which changes in attitudes and practices were reflected in actions taken by hospitals or licensing boards, which are reported in the National Practitioner Data Bank,” Lisa Rotenstein, MD, a primary care physician at Boston’s Brigham and Women’s Hospital and lead author of the study, told this news organization.

Dr. Rotenstein, who is an assistant professor at Harvard Medical School, Boston, studies issues of mental health among physicians and trainees. Dr. Rotenstein was the lead author of a 2016 study that found that more than a quarter (27.2%) of medical students have depressive symptoms. She was also lead author of a 2018 study published in JAMA on the prevalence of burnout among attending physicians.
 

Actions against physicians trending downward

2011 marked the peak in actions taken against physicians’ licenses for substance use, per the study, but actions related to substance use have otherwise maintained a steady decline over the past 17 years. Researchers found that physicians with license actions as a result of substance use or psychological impairment were more likely to receive indefinite penalties, while also having emergency action taken against their license to practice.

In addition, physicians who had actions taken against their licenses because of substance use or psychological impairment were more likely to accrue a greater number of actions over the course of their careers, according to the study.

About 47% of physicians reported experiencing burnout per Medscape’s Physician Burnout and Depression Report 2022: Stress, Anxiety, and Anger report. Burnout among emergency physicians spiked from 43% in 2020 to 60% in 2021, according to the report.

More than one quarter (26%) of physicians reported drinking alcohol to cope with burnout in 2020, according to Medscape’s 2021 Physician Burnout and Suicide Report. Per the 2021 report, 48% of physicians chose exercise to deal with burnout, while 35% indulged in eating junk food.

Peter Grinspoon, MD, a Boston-based primary care physician, wrote in The Los Angeles Times in 2016 that the rate of substance abuse among physicians starts at 10% and can go as high as 15%; by comparison, rates of substance use among the general population are 8%-10%. “What appears to account for the difference is physician distress, and in the case of drug abuse, plentiful access,” he added.

Dr. Grinspoon wrote a 2016 book called “Free Refills: A Doctor Confronts His Addiction,” which chronicles his experience in recovery and relapse as a physician who was dependent on opioid painkillers.

The findings from the recent study in JAMA “suggest we have made some progress in addressing issues related to substance use in ways that don’t result in license actions or even in meeting physicians’ need for support related to substance use,” said Dr. Rotenstein.

Still, she insists that there’s “substantial opportunity to improve mental health and support offerings for physicians and to reduce stigma related to seeking and receiving mental health support, ideally averting the need for license actions.”

According to Dr. Rotenstein, the cases listed in the National Practitioner Data Bank represent the most severe cases; these reports have risen to a high level of attention or concern and are the result of adverse action reports submitted by healthcare institutions and state licensing boards.

“There are many, many more physicians whose cases are not represented here but who struggle with depression, anxiety, substance use, and more,” said Dr. Rotenstein.

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

Actions taken against a physician’s license for substance use are more common than those for psychological impairment or actions related to physical health, according to a recent report. Despite a sharp uptick in 2011, substance use–specific license actions taken against physicians dropped in frequency between 2004 and 2020.

More than three fourths (76.3%) of license actions taken against physicians were related to substance use, according to a recent study published in JAMA. Psychological impairment was the reason associated with more than 1 in 10 (11.5%) actions taken against physicians’ licenses, while physical impairment was the reason behind approximately 12% of such actions, per the study.

Researchers analyzed 5032 actions taken against the licenses of U.S. physicians. The actions were reported to the National Practitioner Data Bank and were related to substance use, psychological impairment, and physical impairment. The National Practitioner Data Bank is a web-based repository of reports with information on medical malpractice payments and certain adverse actions related to healthcare practitioners, providers, and suppliers. It is provided by the Department of Health & Human Services.

“While there has been increased attention [on] the mental health of physicians, we wanted to understand the extent to which changes in attitudes and practices were reflected in actions taken by hospitals or licensing boards, which are reported in the National Practitioner Data Bank,” Lisa Rotenstein, MD, a primary care physician at Boston’s Brigham and Women’s Hospital and lead author of the study, told this news organization.

Dr. Rotenstein, who is an assistant professor at Harvard Medical School, Boston, studies issues of mental health among physicians and trainees. Dr. Rotenstein was the lead author of a 2016 study that found that more than a quarter (27.2%) of medical students have depressive symptoms. She was also lead author of a 2018 study published in JAMA on the prevalence of burnout among attending physicians.
 

Actions against physicians trending downward

2011 marked the peak in actions taken against physicians’ licenses for substance use, per the study, but actions related to substance use have otherwise maintained a steady decline over the past 17 years. Researchers found that physicians with license actions as a result of substance use or psychological impairment were more likely to receive indefinite penalties, while also having emergency action taken against their license to practice.

In addition, physicians who had actions taken against their licenses because of substance use or psychological impairment were more likely to accrue a greater number of actions over the course of their careers, according to the study.

About 47% of physicians reported experiencing burnout per Medscape’s Physician Burnout and Depression Report 2022: Stress, Anxiety, and Anger report. Burnout among emergency physicians spiked from 43% in 2020 to 60% in 2021, according to the report.

More than one quarter (26%) of physicians reported drinking alcohol to cope with burnout in 2020, according to Medscape’s 2021 Physician Burnout and Suicide Report. Per the 2021 report, 48% of physicians chose exercise to deal with burnout, while 35% indulged in eating junk food.

Peter Grinspoon, MD, a Boston-based primary care physician, wrote in The Los Angeles Times in 2016 that the rate of substance abuse among physicians starts at 10% and can go as high as 15%; by comparison, rates of substance use among the general population are 8%-10%. “What appears to account for the difference is physician distress, and in the case of drug abuse, plentiful access,” he added.

Dr. Grinspoon wrote a 2016 book called “Free Refills: A Doctor Confronts His Addiction,” which chronicles his experience in recovery and relapse as a physician who was dependent on opioid painkillers.

The findings from the recent study in JAMA “suggest we have made some progress in addressing issues related to substance use in ways that don’t result in license actions or even in meeting physicians’ need for support related to substance use,” said Dr. Rotenstein.

Still, she insists that there’s “substantial opportunity to improve mental health and support offerings for physicians and to reduce stigma related to seeking and receiving mental health support, ideally averting the need for license actions.”

According to Dr. Rotenstein, the cases listed in the National Practitioner Data Bank represent the most severe cases; these reports have risen to a high level of attention or concern and are the result of adverse action reports submitted by healthcare institutions and state licensing boards.

“There are many, many more physicians whose cases are not represented here but who struggle with depression, anxiety, substance use, and more,” said Dr. Rotenstein.

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

Although it has been used as an ingredient in sunscreens and other personal care products since the 1980s, benzophenone-3 (BP-3) or oxybenzone has emerged in recent years as a significant environmental and health contaminant. DiNardo and Downs point out that BP-3 has been linked to contact and photocontact allergies in humans and implicated as a potential endocrine disruptor. They add that it can yield deleterious by-products when reacting with chlorine in swimming pools and wastewater treatment plants and can cause additional side effects in humans who ingest fish.¹ This column will focus on recent studies, mainly on the role of benzophenones in sunscreen agents that pose considerable risks to waterways and marine life, with concomitant effects on the food chain.

Environmental effects of BPs and legislative responses

Various UV filters, including BP-3, octinoxate, octocrylene, and ethylhexyl salicylate, are thought to pose considerable peril to the marine environment.^2,3 In particular, BP-3 has been demonstrated to provoke coral reef bleaching in vitro, leading to ossification and deforming DNA in the larval stage.^3,4

According to a 2018 report, BP-3 is believed to be present in approximately two thirds of organic sunscreens used in the United States.³ In addition, several studies have revealed that detectable levels of organic sunscreen ingredients, including BP-3, have been identified in coastal waters around the globe, including Hawaii and the U.S. Virgin Islands.^4-8

M Swiet Productions/Moment/Getty Images

A surfeit of tourists has been blamed in part, given that an estimated 25% of applied sunscreen is eliminated within 20 minutes of entering the water and thought to release about 4,000-6,000 tons/year into the surrounding coral reefs.^9,10 In Hawaii in particular, sewage contamination of the waterways has resulted from wastewater treatment facilities ill-equipped to filter out organic substances such as BP-3 and octinoxate.^10,11 In light of such circumstances, the use of sunscreens containing BP-3 and octinoxate have been restricted in Hawaii, particularly in proximity to beaches, since Jan. 1, 2021, because of their apparent environmental impact.¹⁰

The exposure of coral to these compounds is believed to result in bleaching because of impaired membrane integrity and photosynthetic pigment loss in the zooxanthellae that coral releases.^9,10 Coral and the algae zooxanthellae have a symbiotic relationship, Siller et al. explain, with the coral delivering protection and components essential for photosynthesis and the algae ultimately serving as nutrients for the coral.¹⁰ Stress endured by coral is believed to cause algae to detach, rendering coral more vulnerable to disease and less viable overall.¹⁰

In 2016, Downs et al. showed that four out of five sampled locations had detectable levels of BP-3 (100 pp trillion) with a fifth tested site measured at 19.2 pp billion.⁴

In 2019, Sirois acknowledges the problem of coral bleaching around the world but speculates that banning sunscreen ingredients for this purpose will delude people that such a measure will reverse the decline of coral and may lead to the unintended consequence of lower use of sunscreens. Sirois adds that a more comprehensive investigation of the multiple causes of coral reef bleaching is warranted, as are deeper examinations of studies using higher concentrations of sunscreen ingredients in artificial conditions.¹²

In the same year, Raffa et al. discussed the impending ban in Hawaii of the two sunscreen ingredients (BP-3 and octinoxate) to help preserve coral reefs. In so doing, they detailed the natural and human-induced harm to coral reefs, including pollution, fishing practices, overall impact of global climate change, and alterations in ocean temperature and chemistry. The implication is that sunscreen ingredients, which help prevent sun damage in users, are not the only causes of harm to coral reefs. Nevertheless, they point out that concentration estimates and mechanism studies buttress the argument that sunscreen ingredients contribute to coral bleaching. Still, the ban in Hawaii is thought to be a trend. Opponents of the ban are concerned that human skin cancers will rise in such circumstances. Alternative chemical sunscreens are being investigated, and physical sunscreens have emerged as the go-to recommendation.¹³

Notably, oxybenzone has been virtually replaced in the European Union with other UV filters with broad-spectrum action, but the majority of such filters have not yet been approved for use in the United States by the Food and Drug Administration.³

Food chain implications

BP-3 and other UV filters have been investigated for their effects on fish and mammals. Schneider and Lim illustrate that BP-3 is among the frequently used organic UV filters (along with 4-methylbenzylidene camphor, octocrylene, and octinoxate [ethylhexyl methoxycinnamate]) found in most water sources in the world, as well as multiple fish species.2 Cod liver in Norway, for instance, was found to contain octocrylene in 80% of cod, with BP-3 identified in 50% of the sample. BP-3 and octinoxate were also found in white fish.2,14 In laboratory studies, BP-3 in particular has been found in high concentrations in rainbow trout and Japanese rice fish (medaka), causing reduced egg production and hatchlings in females and increased vitellogenin protein production in males, suggesting potential feminization.^2,15

Schneider and Lim note that standard wastewater treatment approaches cannot address this issue and the presence of such contaminants in fish can pose dangerous ramifications in the food chain. They assert that, despite relatively low concentrations in the fish, bioaccumulation and biomagnification present the potential for chemicals accumulating over time and becoming more deleterious as such ingredients travel up the food chain. As higher-chain organisms absorb higher concentrations of the chemicals not broken down in the lower-chain organisms, though, there have not yet been reports of adverse effects of biomagnification in humans.²

BP-3 has been found by Brausch and Rand to have bioaccumulated in fish at higher levels than the ambient water, however.^1,2,16 Schneider and Lim present these issues as relevant to the sun protection discussion, while advocating for dermatologists to continue to counsel wise sun-protective behaviors.²

Conclusion

While calls for additional research are necessary and encouraging, I think human, and likely environmental, health would be better protected by the use of inorganic sunscreens in general and near or in coastal waterways. In light of legislative actions, in particular, it is important for dermatologists to intervene to ensure that patients do not engage in riskier behaviors in the sun in areas facing imminent organic sunscreen bans.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. DiNardo JC and Downs CA. J Cosmet Dermatol. 2018 Feb;17(1):15-9.

2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.

3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.

4. Downs CA et al. Arch Environ Contam Toxicol 2016 Feb;70(2):265-88.

5. Sánchez Rodríguez A et al. Chemosphere. 2015 Jul;131:85-90.

6. Tovar-Sánchez A et al. PLoS One. 2013 Jun 5;8(6):e65451.

7. Danovaro R and Corinaldesi C. Microb Ecol. 2003 Feb;45(2):109-18.

8. Daughton CG and Ternes TA. Environ Health Perspect. 1999 Dec;107 Suppl 6:907-38.

9. Danovaro R et al. Environ Health Perspect. 2008 Apr;116(4):441-7.

10. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.

11. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.

12. Sirois J. Sci Total Environ. 2019 Jul 15;674:211-2.

13. Raffa RB et al. J Clin Pharm Ther. 2019 Feb;44(1):134-9.

14. Langford KH et al. Environ Int. 2015 Jul;80:1-7.

15. Coronado M et al. Aquat Toxicol. 2008 Nov 21;90(3):182-7.

16. Brausch JM and Rand GM. Chemosphere. 2011 Mar;82(11):1518-32.

Although it has been used as an ingredient in sunscreens and other personal care products since the 1980s, benzophenone-3 (BP-3) or oxybenzone has emerged in recent years as a significant environmental and health contaminant. DiNardo and Downs point out that BP-3 has been linked to contact and photocontact allergies in humans and implicated as a potential endocrine disruptor. They add that it can yield deleterious by-products when reacting with chlorine in swimming pools and wastewater treatment plants and can cause additional side effects in humans who ingest fish.¹ This column will focus on recent studies, mainly on the role of benzophenones in sunscreen agents that pose considerable risks to waterways and marine life, with concomitant effects on the food chain.

Environmental effects of BPs and legislative responses

Various UV filters, including BP-3, octinoxate, octocrylene, and ethylhexyl salicylate, are thought to pose considerable peril to the marine environment.^2,3 In particular, BP-3 has been demonstrated to provoke coral reef bleaching in vitro, leading to ossification and deforming DNA in the larval stage.^3,4

According to a 2018 report, BP-3 is believed to be present in approximately two thirds of organic sunscreens used in the United States.³ In addition, several studies have revealed that detectable levels of organic sunscreen ingredients, including BP-3, have been identified in coastal waters around the globe, including Hawaii and the U.S. Virgin Islands.^4-8

M Swiet Productions/Moment/Getty Images

A surfeit of tourists has been blamed in part, given that an estimated 25% of applied sunscreen is eliminated within 20 minutes of entering the water and thought to release about 4,000-6,000 tons/year into the surrounding coral reefs.^9,10 In Hawaii in particular, sewage contamination of the waterways has resulted from wastewater treatment facilities ill-equipped to filter out organic substances such as BP-3 and octinoxate.^10,11 In light of such circumstances, the use of sunscreens containing BP-3 and octinoxate have been restricted in Hawaii, particularly in proximity to beaches, since Jan. 1, 2021, because of their apparent environmental impact.¹⁰

The exposure of coral to these compounds is believed to result in bleaching because of impaired membrane integrity and photosynthetic pigment loss in the zooxanthellae that coral releases.^9,10 Coral and the algae zooxanthellae have a symbiotic relationship, Siller et al. explain, with the coral delivering protection and components essential for photosynthesis and the algae ultimately serving as nutrients for the coral.¹⁰ Stress endured by coral is believed to cause algae to detach, rendering coral more vulnerable to disease and less viable overall.¹⁰

In 2016, Downs et al. showed that four out of five sampled locations had detectable levels of BP-3 (100 pp trillion) with a fifth tested site measured at 19.2 pp billion.⁴

In 2019, Sirois acknowledges the problem of coral bleaching around the world but speculates that banning sunscreen ingredients for this purpose will delude people that such a measure will reverse the decline of coral and may lead to the unintended consequence of lower use of sunscreens. Sirois adds that a more comprehensive investigation of the multiple causes of coral reef bleaching is warranted, as are deeper examinations of studies using higher concentrations of sunscreen ingredients in artificial conditions.¹²

In the same year, Raffa et al. discussed the impending ban in Hawaii of the two sunscreen ingredients (BP-3 and octinoxate) to help preserve coral reefs. In so doing, they detailed the natural and human-induced harm to coral reefs, including pollution, fishing practices, overall impact of global climate change, and alterations in ocean temperature and chemistry. The implication is that sunscreen ingredients, which help prevent sun damage in users, are not the only causes of harm to coral reefs. Nevertheless, they point out that concentration estimates and mechanism studies buttress the argument that sunscreen ingredients contribute to coral bleaching. Still, the ban in Hawaii is thought to be a trend. Opponents of the ban are concerned that human skin cancers will rise in such circumstances. Alternative chemical sunscreens are being investigated, and physical sunscreens have emerged as the go-to recommendation.¹³

Notably, oxybenzone has been virtually replaced in the European Union with other UV filters with broad-spectrum action, but the majority of such filters have not yet been approved for use in the United States by the Food and Drug Administration.³

Food chain implications

BP-3 and other UV filters have been investigated for their effects on fish and mammals. Schneider and Lim illustrate that BP-3 is among the frequently used organic UV filters (along with 4-methylbenzylidene camphor, octocrylene, and octinoxate [ethylhexyl methoxycinnamate]) found in most water sources in the world, as well as multiple fish species.2 Cod liver in Norway, for instance, was found to contain octocrylene in 80% of cod, with BP-3 identified in 50% of the sample. BP-3 and octinoxate were also found in white fish.2,14 In laboratory studies, BP-3 in particular has been found in high concentrations in rainbow trout and Japanese rice fish (medaka), causing reduced egg production and hatchlings in females and increased vitellogenin protein production in males, suggesting potential feminization.^2,15

Schneider and Lim note that standard wastewater treatment approaches cannot address this issue and the presence of such contaminants in fish can pose dangerous ramifications in the food chain. They assert that, despite relatively low concentrations in the fish, bioaccumulation and biomagnification present the potential for chemicals accumulating over time and becoming more deleterious as such ingredients travel up the food chain. As higher-chain organisms absorb higher concentrations of the chemicals not broken down in the lower-chain organisms, though, there have not yet been reports of adverse effects of biomagnification in humans.²

BP-3 has been found by Brausch and Rand to have bioaccumulated in fish at higher levels than the ambient water, however.^1,2,16 Schneider and Lim present these issues as relevant to the sun protection discussion, while advocating for dermatologists to continue to counsel wise sun-protective behaviors.²

Conclusion

While calls for additional research are necessary and encouraging, I think human, and likely environmental, health would be better protected by the use of inorganic sunscreens in general and near or in coastal waterways. In light of legislative actions, in particular, it is important for dermatologists to intervene to ensure that patients do not engage in riskier behaviors in the sun in areas facing imminent organic sunscreen bans.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. DiNardo JC and Downs CA. J Cosmet Dermatol. 2018 Feb;17(1):15-9.

2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.

3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.

4. Downs CA et al. Arch Environ Contam Toxicol 2016 Feb;70(2):265-88.

5. Sánchez Rodríguez A et al. Chemosphere. 2015 Jul;131:85-90.

6. Tovar-Sánchez A et al. PLoS One. 2013 Jun 5;8(6):e65451.

7. Danovaro R and Corinaldesi C. Microb Ecol. 2003 Feb;45(2):109-18.

8. Daughton CG and Ternes TA. Environ Health Perspect. 1999 Dec;107 Suppl 6:907-38.

9. Danovaro R et al. Environ Health Perspect. 2008 Apr;116(4):441-7.

10. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.

11. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.

12. Sirois J. Sci Total Environ. 2019 Jul 15;674:211-2.

13. Raffa RB et al. J Clin Pharm Ther. 2019 Feb;44(1):134-9.

14. Langford KH et al. Environ Int. 2015 Jul;80:1-7.

15. Coronado M et al. Aquat Toxicol. 2008 Nov 21;90(3):182-7.

16. Brausch JM and Rand GM. Chemosphere. 2011 Mar;82(11):1518-32.

Although it has been used as an ingredient in sunscreens and other personal care products since the 1980s, benzophenone-3 (BP-3) or oxybenzone has emerged in recent years as a significant environmental and health contaminant. DiNardo and Downs point out that BP-3 has been linked to contact and photocontact allergies in humans and implicated as a potential endocrine disruptor. They add that it can yield deleterious by-products when reacting with chlorine in swimming pools and wastewater treatment plants and can cause additional side effects in humans who ingest fish.¹ This column will focus on recent studies, mainly on the role of benzophenones in sunscreen agents that pose considerable risks to waterways and marine life, with concomitant effects on the food chain.

Environmental effects of BPs and legislative responses

Various UV filters, including BP-3, octinoxate, octocrylene, and ethylhexyl salicylate, are thought to pose considerable peril to the marine environment.^2,3 In particular, BP-3 has been demonstrated to provoke coral reef bleaching in vitro, leading to ossification and deforming DNA in the larval stage.^3,4

According to a 2018 report, BP-3 is believed to be present in approximately two thirds of organic sunscreens used in the United States.³ In addition, several studies have revealed that detectable levels of organic sunscreen ingredients, including BP-3, have been identified in coastal waters around the globe, including Hawaii and the U.S. Virgin Islands.^4-8

M Swiet Productions/Moment/Getty Images

A surfeit of tourists has been blamed in part, given that an estimated 25% of applied sunscreen is eliminated within 20 minutes of entering the water and thought to release about 4,000-6,000 tons/year into the surrounding coral reefs.^9,10 In Hawaii in particular, sewage contamination of the waterways has resulted from wastewater treatment facilities ill-equipped to filter out organic substances such as BP-3 and octinoxate.^10,11 In light of such circumstances, the use of sunscreens containing BP-3 and octinoxate have been restricted in Hawaii, particularly in proximity to beaches, since Jan. 1, 2021, because of their apparent environmental impact.¹⁰

The exposure of coral to these compounds is believed to result in bleaching because of impaired membrane integrity and photosynthetic pigment loss in the zooxanthellae that coral releases.^9,10 Coral and the algae zooxanthellae have a symbiotic relationship, Siller et al. explain, with the coral delivering protection and components essential for photosynthesis and the algae ultimately serving as nutrients for the coral.¹⁰ Stress endured by coral is believed to cause algae to detach, rendering coral more vulnerable to disease and less viable overall.¹⁰

In 2016, Downs et al. showed that four out of five sampled locations had detectable levels of BP-3 (100 pp trillion) with a fifth tested site measured at 19.2 pp billion.⁴

In 2019, Sirois acknowledges the problem of coral bleaching around the world but speculates that banning sunscreen ingredients for this purpose will delude people that such a measure will reverse the decline of coral and may lead to the unintended consequence of lower use of sunscreens. Sirois adds that a more comprehensive investigation of the multiple causes of coral reef bleaching is warranted, as are deeper examinations of studies using higher concentrations of sunscreen ingredients in artificial conditions.¹²

In the same year, Raffa et al. discussed the impending ban in Hawaii of the two sunscreen ingredients (BP-3 and octinoxate) to help preserve coral reefs. In so doing, they detailed the natural and human-induced harm to coral reefs, including pollution, fishing practices, overall impact of global climate change, and alterations in ocean temperature and chemistry. The implication is that sunscreen ingredients, which help prevent sun damage in users, are not the only causes of harm to coral reefs. Nevertheless, they point out that concentration estimates and mechanism studies buttress the argument that sunscreen ingredients contribute to coral bleaching. Still, the ban in Hawaii is thought to be a trend. Opponents of the ban are concerned that human skin cancers will rise in such circumstances. Alternative chemical sunscreens are being investigated, and physical sunscreens have emerged as the go-to recommendation.¹³

Notably, oxybenzone has been virtually replaced in the European Union with other UV filters with broad-spectrum action, but the majority of such filters have not yet been approved for use in the United States by the Food and Drug Administration.³

Food chain implications

BP-3 and other UV filters have been investigated for their effects on fish and mammals. Schneider and Lim illustrate that BP-3 is among the frequently used organic UV filters (along with 4-methylbenzylidene camphor, octocrylene, and octinoxate [ethylhexyl methoxycinnamate]) found in most water sources in the world, as well as multiple fish species.2 Cod liver in Norway, for instance, was found to contain octocrylene in 80% of cod, with BP-3 identified in 50% of the sample. BP-3 and octinoxate were also found in white fish.2,14 In laboratory studies, BP-3 in particular has been found in high concentrations in rainbow trout and Japanese rice fish (medaka), causing reduced egg production and hatchlings in females and increased vitellogenin protein production in males, suggesting potential feminization.^2,15

Schneider and Lim note that standard wastewater treatment approaches cannot address this issue and the presence of such contaminants in fish can pose dangerous ramifications in the food chain. They assert that, despite relatively low concentrations in the fish, bioaccumulation and biomagnification present the potential for chemicals accumulating over time and becoming more deleterious as such ingredients travel up the food chain. As higher-chain organisms absorb higher concentrations of the chemicals not broken down in the lower-chain organisms, though, there have not yet been reports of adverse effects of biomagnification in humans.²

BP-3 has been found by Brausch and Rand to have bioaccumulated in fish at higher levels than the ambient water, however.^1,2,16 Schneider and Lim present these issues as relevant to the sun protection discussion, while advocating for dermatologists to continue to counsel wise sun-protective behaviors.²

Conclusion

While calls for additional research are necessary and encouraging, I think human, and likely environmental, health would be better protected by the use of inorganic sunscreens in general and near or in coastal waterways. In light of legislative actions, in particular, it is important for dermatologists to intervene to ensure that patients do not engage in riskier behaviors in the sun in areas facing imminent organic sunscreen bans.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. DiNardo JC and Downs CA. J Cosmet Dermatol. 2018 Feb;17(1):15-9.

2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.

3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.

4. Downs CA et al. Arch Environ Contam Toxicol 2016 Feb;70(2):265-88.

5. Sánchez Rodríguez A et al. Chemosphere. 2015 Jul;131:85-90.

6. Tovar-Sánchez A et al. PLoS One. 2013 Jun 5;8(6):e65451.

7. Danovaro R and Corinaldesi C. Microb Ecol. 2003 Feb;45(2):109-18.

8. Daughton CG and Ternes TA. Environ Health Perspect. 1999 Dec;107 Suppl 6:907-38.

9. Danovaro R et al. Environ Health Perspect. 2008 Apr;116(4):441-7.

10. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.

11. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.

12. Sirois J. Sci Total Environ. 2019 Jul 15;674:211-2.

13. Raffa RB et al. J Clin Pharm Ther. 2019 Feb;44(1):134-9.

14. Langford KH et al. Environ Int. 2015 Jul;80:1-7.

15. Coronado M et al. Aquat Toxicol. 2008 Nov 21;90(3):182-7.

16. Brausch JM and Rand GM. Chemosphere. 2011 Mar;82(11):1518-32.