Dermatology News

PARIS – Air pollution has been recognized as a risk factor for lung cancer for about 2 decades, and investigators in the UK have now identified a potential mechanism whereby the air we breathe may trigger driver mutations already present in normal lung cells to cause cancer.

Think of it as “smoking gun–level” evidence that may explain why many nonsmokers still develop non–small cell lung cancer, said Charles Swanton, PhD, from the Francis Crick Institute and Cancer Research UK Chief Clinician, London.

“What this work shows is that air pollution is directly causing lung cancer but through a slightly unexpected pathway,” he said at a briefing prior to his presentation of the data in a presidential symposium held earlier this month in Paris at the European Society for Medical Oncology Congress 2022.

Importantly, he and his team also propose a mechanism for blocking the effects of air pollution with monoclonal antibodies directed against the inflammatory cytokine interleukein-1 beta.
 

Carcinogenesis explored

Lung cancer in never-smokers has a low mutational burden, with about 5- to 10-fold fewer mutations in a nonsmoker, compared with an ever smoker or current smoker, Dr. Swanton noted.

“The other thing to say about never-smokers is that they don’t have a clear environmental carcinogenic signature. So how do you square the circle? You’ve got the problem that you know that air pollution is associated with lung cancer – we don’t know if it causes it – but we also see that we’ve got no DNA mutations due to an environmental carcinogen,” he said during his symposium presentation.

The traditional model proposed to explain how carcinogens cause cancer holds that exposure to a carcinogen causes DNA mutations that lead to clonal expansion and tumor growth.

“But there are some major problems with this model,” Dr. Swanton said.

For example, normal skin contains a “patchwork of mutant clones,” but skin cancer is still uncommon, he said, and in studies in mice, 17 of 20 environmental carcinogens did not induce DNA mutations. He also noted that a common melanoma driver mutation, BRAF V600E, is not induced by exposure to a ultraviolet light.

“Any explanation for never-smoking lung cancer would have to fulfill three criteria: one, you have to explain why geographic variation exists; two, you have to prove causation; and three, you have to explain how cancers can be initiated without directly causing DNA mutations,” he said.

Normal lung tissues in nonsmoking adults can harbor pre-existing mutations, with the number of mutations increasing likely as a consequence of aging. In fact, more than 50% of normal lung biopsy tissues have been shown to harbor driver KRAS and/or EGFR mutations, Dr. Swanton said.

“In our research, these mutations alone only weakly potentiated cancer in laboratory models. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harboring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t,” he said.
 

Geographical exposures

Looking at data on 447,932 participants in the UK Biobank, the investigators found that increasing exposure to ambient air particles smaller than 2.5 mcm (PM_2.5) was significantly associated with seven cancer types, including lung cancer. They also saw an association between PM­­_2.5 exposure levels and EGFR-mutated lung cancer incidence in the United Kingdom, South Korea, and Taiwan.

And crucially, as Dr. Swanton and associates showed in mouse models, exposure of lung cells bearing somatic EGFR and KRAS mutations to PM2.5 causes recruitment of macrophages that in turn secrete IL-1B, resulting in a transdifferentiation of EGFR-mutated cells into a cancer stem cell state, and tumor formation.

Importantly, pollution-induced tumor formation can be blocked by antibodies directed against IL-1B, Dr. Swanton said.

He pointed to a 2017 study in The Lancet suggesting that anti-inflammatory therapy with the anti–IL-1 antibody canakinumab (Ilaris) could reduce incident lung cancer and lung cancer deaths.
 

‘Elegant first demonstration’

“This is a very meaningful demonstration, from epidemiological data to preclinical models of the role of PM_­2.5 air pollutants in the promotion of lung cancer, and it provides us with very important insights into the mechanism through which nonsmokers can get lung cancer,” commented Suzette Delaloge, MD, from the cancer interception program at Institut Goustave Roussy in Villejuif, France, the invited discussant.

“But beyond that, it also has a great impact on our vision of carcinogenesis, with this very elegant first demonstration of the alternative nonmutagenic, carcinogenetic promotion hypothesis for fine particulate matter,” she said.

Questions still to be answered include whether PM_2.5 pollutants could also be mutagenic, is the oncogenic pathway ubiquitous in tissue, which components of PM_2.5 might drive the effect, how long of an exposure is required to promote lung cancer, and why and how persons without cancer develop specific driver mutations such as EGFR, she said.

“This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for precancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1B inhibitors,” said Tony Mok, MD, a lung cancer specialist at the Chinese University of Hong Kong, who was not involved in the study.

“We don’t yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find nonsmokers who are predisposed to lung cancer and may benefit from lung scanning, so discussions are still very speculative,” he said in a statement.

The study was supported by Cancer Research UK, the Lung Cancer Research Foundations, Rosetrees Trust, the Mark Foundation for Cancer Research and the Ruth Strauss Foundation. Dr. Swanton disclosed grants/research support, honoraria, and stock ownership with multiple entities. Dr. Delaloge disclosed institutional financing and research funding from multiple companies. Dr. Mok disclosed stock ownership and honoraria with multiple companies.

PARIS – Air pollution has been recognized as a risk factor for lung cancer for about 2 decades, and investigators in the UK have now identified a potential mechanism whereby the air we breathe may trigger driver mutations already present in normal lung cells to cause cancer.

Think of it as “smoking gun–level” evidence that may explain why many nonsmokers still develop non–small cell lung cancer, said Charles Swanton, PhD, from the Francis Crick Institute and Cancer Research UK Chief Clinician, London.

“What this work shows is that air pollution is directly causing lung cancer but through a slightly unexpected pathway,” he said at a briefing prior to his presentation of the data in a presidential symposium held earlier this month in Paris at the European Society for Medical Oncology Congress 2022.

Importantly, he and his team also propose a mechanism for blocking the effects of air pollution with monoclonal antibodies directed against the inflammatory cytokine interleukein-1 beta.
 

Carcinogenesis explored

Lung cancer in never-smokers has a low mutational burden, with about 5- to 10-fold fewer mutations in a nonsmoker, compared with an ever smoker or current smoker, Dr. Swanton noted.

“The other thing to say about never-smokers is that they don’t have a clear environmental carcinogenic signature. So how do you square the circle? You’ve got the problem that you know that air pollution is associated with lung cancer – we don’t know if it causes it – but we also see that we’ve got no DNA mutations due to an environmental carcinogen,” he said during his symposium presentation.

The traditional model proposed to explain how carcinogens cause cancer holds that exposure to a carcinogen causes DNA mutations that lead to clonal expansion and tumor growth.

“But there are some major problems with this model,” Dr. Swanton said.

For example, normal skin contains a “patchwork of mutant clones,” but skin cancer is still uncommon, he said, and in studies in mice, 17 of 20 environmental carcinogens did not induce DNA mutations. He also noted that a common melanoma driver mutation, BRAF V600E, is not induced by exposure to a ultraviolet light.

“Any explanation for never-smoking lung cancer would have to fulfill three criteria: one, you have to explain why geographic variation exists; two, you have to prove causation; and three, you have to explain how cancers can be initiated without directly causing DNA mutations,” he said.

Normal lung tissues in nonsmoking adults can harbor pre-existing mutations, with the number of mutations increasing likely as a consequence of aging. In fact, more than 50% of normal lung biopsy tissues have been shown to harbor driver KRAS and/or EGFR mutations, Dr. Swanton said.

“In our research, these mutations alone only weakly potentiated cancer in laboratory models. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harboring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t,” he said.
 

Geographical exposures

Looking at data on 447,932 participants in the UK Biobank, the investigators found that increasing exposure to ambient air particles smaller than 2.5 mcm (PM_2.5) was significantly associated with seven cancer types, including lung cancer. They also saw an association between PM­­_2.5 exposure levels and EGFR-mutated lung cancer incidence in the United Kingdom, South Korea, and Taiwan.

And crucially, as Dr. Swanton and associates showed in mouse models, exposure of lung cells bearing somatic EGFR and KRAS mutations to PM2.5 causes recruitment of macrophages that in turn secrete IL-1B, resulting in a transdifferentiation of EGFR-mutated cells into a cancer stem cell state, and tumor formation.

Importantly, pollution-induced tumor formation can be blocked by antibodies directed against IL-1B, Dr. Swanton said.

He pointed to a 2017 study in The Lancet suggesting that anti-inflammatory therapy with the anti–IL-1 antibody canakinumab (Ilaris) could reduce incident lung cancer and lung cancer deaths.
 

‘Elegant first demonstration’

“This is a very meaningful demonstration, from epidemiological data to preclinical models of the role of PM_­2.5 air pollutants in the promotion of lung cancer, and it provides us with very important insights into the mechanism through which nonsmokers can get lung cancer,” commented Suzette Delaloge, MD, from the cancer interception program at Institut Goustave Roussy in Villejuif, France, the invited discussant.

“But beyond that, it also has a great impact on our vision of carcinogenesis, with this very elegant first demonstration of the alternative nonmutagenic, carcinogenetic promotion hypothesis for fine particulate matter,” she said.

Questions still to be answered include whether PM_2.5 pollutants could also be mutagenic, is the oncogenic pathway ubiquitous in tissue, which components of PM_2.5 might drive the effect, how long of an exposure is required to promote lung cancer, and why and how persons without cancer develop specific driver mutations such as EGFR, she said.

“This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for precancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1B inhibitors,” said Tony Mok, MD, a lung cancer specialist at the Chinese University of Hong Kong, who was not involved in the study.

“We don’t yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find nonsmokers who are predisposed to lung cancer and may benefit from lung scanning, so discussions are still very speculative,” he said in a statement.

The study was supported by Cancer Research UK, the Lung Cancer Research Foundations, Rosetrees Trust, the Mark Foundation for Cancer Research and the Ruth Strauss Foundation. Dr. Swanton disclosed grants/research support, honoraria, and stock ownership with multiple entities. Dr. Delaloge disclosed institutional financing and research funding from multiple companies. Dr. Mok disclosed stock ownership and honoraria with multiple companies.

PARIS – Air pollution has been recognized as a risk factor for lung cancer for about 2 decades, and investigators in the UK have now identified a potential mechanism whereby the air we breathe may trigger driver mutations already present in normal lung cells to cause cancer.

Think of it as “smoking gun–level” evidence that may explain why many nonsmokers still develop non–small cell lung cancer, said Charles Swanton, PhD, from the Francis Crick Institute and Cancer Research UK Chief Clinician, London.

“What this work shows is that air pollution is directly causing lung cancer but through a slightly unexpected pathway,” he said at a briefing prior to his presentation of the data in a presidential symposium held earlier this month in Paris at the European Society for Medical Oncology Congress 2022.

Importantly, he and his team also propose a mechanism for blocking the effects of air pollution with monoclonal antibodies directed against the inflammatory cytokine interleukein-1 beta.
 

Carcinogenesis explored

Lung cancer in never-smokers has a low mutational burden, with about 5- to 10-fold fewer mutations in a nonsmoker, compared with an ever smoker or current smoker, Dr. Swanton noted.

“The other thing to say about never-smokers is that they don’t have a clear environmental carcinogenic signature. So how do you square the circle? You’ve got the problem that you know that air pollution is associated with lung cancer – we don’t know if it causes it – but we also see that we’ve got no DNA mutations due to an environmental carcinogen,” he said during his symposium presentation.

The traditional model proposed to explain how carcinogens cause cancer holds that exposure to a carcinogen causes DNA mutations that lead to clonal expansion and tumor growth.

“But there are some major problems with this model,” Dr. Swanton said.

For example, normal skin contains a “patchwork of mutant clones,” but skin cancer is still uncommon, he said, and in studies in mice, 17 of 20 environmental carcinogens did not induce DNA mutations. He also noted that a common melanoma driver mutation, BRAF V600E, is not induced by exposure to a ultraviolet light.

“Any explanation for never-smoking lung cancer would have to fulfill three criteria: one, you have to explain why geographic variation exists; two, you have to prove causation; and three, you have to explain how cancers can be initiated without directly causing DNA mutations,” he said.

Normal lung tissues in nonsmoking adults can harbor pre-existing mutations, with the number of mutations increasing likely as a consequence of aging. In fact, more than 50% of normal lung biopsy tissues have been shown to harbor driver KRAS and/or EGFR mutations, Dr. Swanton said.

“In our research, these mutations alone only weakly potentiated cancer in laboratory models. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harboring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t,” he said.
 

Geographical exposures

Looking at data on 447,932 participants in the UK Biobank, the investigators found that increasing exposure to ambient air particles smaller than 2.5 mcm (PM_2.5) was significantly associated with seven cancer types, including lung cancer. They also saw an association between PM­­_2.5 exposure levels and EGFR-mutated lung cancer incidence in the United Kingdom, South Korea, and Taiwan.

And crucially, as Dr. Swanton and associates showed in mouse models, exposure of lung cells bearing somatic EGFR and KRAS mutations to PM2.5 causes recruitment of macrophages that in turn secrete IL-1B, resulting in a transdifferentiation of EGFR-mutated cells into a cancer stem cell state, and tumor formation.

Importantly, pollution-induced tumor formation can be blocked by antibodies directed against IL-1B, Dr. Swanton said.

He pointed to a 2017 study in The Lancet suggesting that anti-inflammatory therapy with the anti–IL-1 antibody canakinumab (Ilaris) could reduce incident lung cancer and lung cancer deaths.
 

‘Elegant first demonstration’

“This is a very meaningful demonstration, from epidemiological data to preclinical models of the role of PM_­2.5 air pollutants in the promotion of lung cancer, and it provides us with very important insights into the mechanism through which nonsmokers can get lung cancer,” commented Suzette Delaloge, MD, from the cancer interception program at Institut Goustave Roussy in Villejuif, France, the invited discussant.

“But beyond that, it also has a great impact on our vision of carcinogenesis, with this very elegant first demonstration of the alternative nonmutagenic, carcinogenetic promotion hypothesis for fine particulate matter,” she said.

Questions still to be answered include whether PM_2.5 pollutants could also be mutagenic, is the oncogenic pathway ubiquitous in tissue, which components of PM_2.5 might drive the effect, how long of an exposure is required to promote lung cancer, and why and how persons without cancer develop specific driver mutations such as EGFR, she said.

“This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for precancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1B inhibitors,” said Tony Mok, MD, a lung cancer specialist at the Chinese University of Hong Kong, who was not involved in the study.

“We don’t yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find nonsmokers who are predisposed to lung cancer and may benefit from lung scanning, so discussions are still very speculative,” he said in a statement.

The study was supported by Cancer Research UK, the Lung Cancer Research Foundations, Rosetrees Trust, the Mark Foundation for Cancer Research and the Ruth Strauss Foundation. Dr. Swanton disclosed grants/research support, honoraria, and stock ownership with multiple entities. Dr. Delaloge disclosed institutional financing and research funding from multiple companies. Dr. Mok disclosed stock ownership and honoraria with multiple companies.

The Food and Drug Administration has issued a safety alert, warning of a rare but concerning potential risk of squamous cell carcinoma (SCC) and various lymphomas in the scar tissue around breast implants.

The FDA safety communication is based on several dozen reports of these cancers occurring in the capsule or scar tissue around breast implants. This issue differs from breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) – a known risk among implant recipients.

“After preliminary review of published literature as part of our ongoing monitoring of the safety of breast implants, the FDA is aware of less than 20 cases of SCC and less than 30 cases of various lymphomas in the capsule around the breast implant,” the agency’s alert explains.

One avenue through which the FDA has identified cases is via medical device reports. As of Sept. 1, the FDA has received 10 medical device reports about SCC related to breast implants and 12 about various lymphomas.

The incidence rate and risk factors for these events are currently unknown, but reports of SCC and various lymphomas in the capsule around the breast implants have been reported for both textured and smooth breast implants, as well as for both saline and silicone breast implants. In some cases, the cancers were diagnosed years after breast implant surgery.

Reported signs and symptoms included swelling, pain, lumps, or skin changes. 

Although the risks of SCC and lymphomas in the tissue around breast implants appears rare, “when safety risks with medical devices are identified, we wanted to provide clear and understandable information to the public as quickly as possible,” Binita Ashar, MD, director of the Office of Surgical and Infection Control Devices, FDA Center for Devices and Radiological Health, explained in a press release.

Patients and providers are strongly encouraged to report breast implant–related problems and cases of SCC or lymphoma of the breast implant capsule to MedWatch, the FDA’s adverse event reporting program.

The FDA plans to complete “a thorough literature review” as well as “identify ways to collect more detailed information regarding patient cases.”

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

The Food and Drug Administration has issued a safety alert, warning of a rare but concerning potential risk of squamous cell carcinoma (SCC) and various lymphomas in the scar tissue around breast implants.

The FDA safety communication is based on several dozen reports of these cancers occurring in the capsule or scar tissue around breast implants. This issue differs from breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) – a known risk among implant recipients.

“After preliminary review of published literature as part of our ongoing monitoring of the safety of breast implants, the FDA is aware of less than 20 cases of SCC and less than 30 cases of various lymphomas in the capsule around the breast implant,” the agency’s alert explains.

One avenue through which the FDA has identified cases is via medical device reports. As of Sept. 1, the FDA has received 10 medical device reports about SCC related to breast implants and 12 about various lymphomas.

The incidence rate and risk factors for these events are currently unknown, but reports of SCC and various lymphomas in the capsule around the breast implants have been reported for both textured and smooth breast implants, as well as for both saline and silicone breast implants. In some cases, the cancers were diagnosed years after breast implant surgery.

Reported signs and symptoms included swelling, pain, lumps, or skin changes. 

Although the risks of SCC and lymphomas in the tissue around breast implants appears rare, “when safety risks with medical devices are identified, we wanted to provide clear and understandable information to the public as quickly as possible,” Binita Ashar, MD, director of the Office of Surgical and Infection Control Devices, FDA Center for Devices and Radiological Health, explained in a press release.

Patients and providers are strongly encouraged to report breast implant–related problems and cases of SCC or lymphoma of the breast implant capsule to MedWatch, the FDA’s adverse event reporting program.

The FDA plans to complete “a thorough literature review” as well as “identify ways to collect more detailed information regarding patient cases.”

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

The Food and Drug Administration has issued a safety alert, warning of a rare but concerning potential risk of squamous cell carcinoma (SCC) and various lymphomas in the scar tissue around breast implants.

The FDA safety communication is based on several dozen reports of these cancers occurring in the capsule or scar tissue around breast implants. This issue differs from breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) – a known risk among implant recipients.

“After preliminary review of published literature as part of our ongoing monitoring of the safety of breast implants, the FDA is aware of less than 20 cases of SCC and less than 30 cases of various lymphomas in the capsule around the breast implant,” the agency’s alert explains.

One avenue through which the FDA has identified cases is via medical device reports. As of Sept. 1, the FDA has received 10 medical device reports about SCC related to breast implants and 12 about various lymphomas.

The incidence rate and risk factors for these events are currently unknown, but reports of SCC and various lymphomas in the capsule around the breast implants have been reported for both textured and smooth breast implants, as well as for both saline and silicone breast implants. In some cases, the cancers were diagnosed years after breast implant surgery.

Reported signs and symptoms included swelling, pain, lumps, or skin changes. 

Although the risks of SCC and lymphomas in the tissue around breast implants appears rare, “when safety risks with medical devices are identified, we wanted to provide clear and understandable information to the public as quickly as possible,” Binita Ashar, MD, director of the Office of Surgical and Infection Control Devices, FDA Center for Devices and Radiological Health, explained in a press release.

Patients and providers are strongly encouraged to report breast implant–related problems and cases of SCC or lymphoma of the breast implant capsule to MedWatch, the FDA’s adverse event reporting program.

The FDA plans to complete “a thorough literature review” as well as “identify ways to collect more detailed information regarding patient cases.”

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

Treatment with the humanized monoclonal antibody litifilimab for patients with systemic lupus erythematosus (SLE) led to greater improvements in joint manifestations than did placebo in an international phase 2 trial that reflects keen interest in targeting type 1 interferon and the innate immune system.

Litifilimab was associated with an approximately three-joint reduction in the number of swollen and tender joints, compared with placebo, over 24 weeks in the study, which was published  in The New England Journal of Medicine.

The study was the first part of the LILAC trial, a two-part, phase 2 study. The second part involved cutaneous lupus erythematosus (CLE) with or without systemic manifestations. Treatment led to improvements in skin disease, as measured by Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores. It was published  in the New England Journal of Medicine.

The investigational drug targets blood dendritic cell antigen 2 (BDCA2). The antigen is expressed solely on plasmacytoid dendritic cells (pDCs), which accumulate in skin lesions and organs of patients with SLE. When the antibody binds to BDCA2, “the synthesis of a variety of cytokines is shut down – type 1 interferons, type 3 interferons, TNF [tumor necrosis factor], and [other cytokines and chemokines] made by the pDCs,” Richard A. Furie, MD, lead author of the article, said in an interview.

In a phase 1 trial involving patients with SLE and CLE, the drug’s biologic activity was shown by a dampened interferon signature in blood and modulated type 1 interferon-induced proteins in the skin, he and his coinvestigators noted.

Dr. Furie is chief of rheumatology at Northwell Health and professor of medicine at the Feinstein Institutes for Medical Research at Northwell and at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York.
 

Impact on the joints

The primary analysis in the SLE trial involved 102 patients who had SLE, arthritis, and active skin disease. The patients received litifilimab 450 mg or placebo, administered subcutaneously, at weeks 0, 2, 4, 8, 12, 16, and 20. The patients were required to have at least four tender joints and at least four swollen joints, and these active joints had to be those classically involved in lupus arthritis.

The mean (± standard deviation) baseline number of active joints was 19 ± 8.4 in the litifilimab group and 21.6 ± 8.5 in placebo group. From baseline to week 24, the least-squares mean (± standard deviation) change in the total number of active joints was –15.0 ± 1.2 with litifilimab and –11.6 ± 1.3 with placebo (mean difference, –3.4; 95% confidence interval, –6.7 to -0.2; P = .04).

Most of the secondary endpoints did not support the results of the primary analysis. However, improvement was seen in the SLE Responder Index (SRI-4) – a three-component global index that Dr. Furie and others developed in 2009 using data from the phase 2 SLE trial of belimumab (Benlysta).

The composite index, used in the phase 3 trial of belimumab, captures improvement in disease activity without a worsening of the condition overall or new significant disease activity in other domains. “It’s a dichotomous measure – either you’re a responder or not,” Dr. Furie said in the interview.

Response on the SRI-4 was defined as a reduction of at least 4 points from baseline in the SLEDAI-2K score (the Systemic Lupus Erythematosus Disease Activity Index), no new disease activity as measured by one score of A (severe) or more than one score of B (moderate) on the BILAG (British Isles Lupus Assessment Group) index, and no increase of 0.3 points or more on the Physician’s Global Assessment.

A total of 56% of the patients in the litifilimab group showed responses on the SRI-4 at week 24, compared with 29% in the placebo group (least-squares mean difference, 26.4%; 95% confidence interval [CI], 9.5-43.2). This is “a robust response” that is much greater than the effect size seen in the phase 3 trial of belimumab or in research on anifrolumab (Saphnelo). Both of those drugs are approved for SLE, Dr. Furie said. “We’ll need to see if it’s reproduced in phase 3.”

There’s “little question that litifilimab works for the skin,” Dr. Furie noted. In the second part of the LILAC study, which focused on CLE, litifilimab demonstrated efficacy, and the SLE trial lends more support. Among several secondary endpoints evaluating skin-related disease activity, a reduction of at least 7 points from baseline in the CLASI-A score (a clinically relevant threshold) occurred in 56% of the litifilimab group and 34% of the placebo group.

The trial was conducted at 55 centers in Asia, Europe, Latin America, and the United States. The SLE part of the study began as a dose-ranging study aimed at evaluating cutaneous lupus activity, but owing to “slow enrollment and to allow an assessment of the effect of litifilimab on arthritis in SLE,” the protocol and primary endpoint were amended before the trial data were unblinded to evaluate only the 450-mg dose among participants with active arthritis and skin disease (at least one active skin lesion), the investigators explained.

Background therapy for SLE was allowed if the therapy was initiated at least 12 weeks before randomization and if dose levels were stable through the trial period. Glucocorticoids had to be tapered to ≤ 10 mg/day according to a specified regimen.

Making progress for lupus

Jane E. Salmon, MD, director of the Lupus and APS Center of Excellence and codirector of the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery in New York, who was not involved in the research, said in an email that she is “cautiously optimistic, because in SLE, successful phase 2 trials too often are followed by unsuccessful phase 3 trials.”

Courtesy Hospital for Special Surgery

Blocking the production of type 1 interferon by pDCs implicated in SLE pathogenesis has the theoretical advantage of preserving type 1 interferon critical to protection from viruses, she noted. Herpes infections were reported among patients who received litifilimab, but rates were not increased, compared with placebo.

Diversity is an important priority in further research, Dr. Salmon said.

Daniel J. Wallace, MD, of Cedars-Sinai Medical Center in Los Angeles, similarly pointed out in an editorial that accompanied the SLE phase 2 trial that while Black patients make up one-third of the U.S. population with lupus, only about 10% of study participants whose race and ethnicity was reported were Black). (Race was not reported by sites in Europe.)

The results of the LILAC trials “encourage further exploration of interventions that affect upstream lupus inflammatory pathways in the innate immune system in lupus,” Dr. Wallace wrote. He noted that lupus has “lagged behind its rheumatic cousins,” such as rheumatoid arthritis and vasculitis, in drug development.

Developing endpoints and study designs for SLE trials has been challenging, at least partly because it is a multisystem disease, Dr. Furie said. “But we’re making progress.”

Anifrolumab, a type 1 interferon receptor monoclonal antibody that was approved for SLE in July 2021, “may have a broader effect on type 1 interferons,” he noted, while litifilimab “may have a broader effect on proinflammatory cytokines, at least those expressed by pDCs.”

Biogen, the sponsor of the LILAC trial, is currently enrolling patients in phase 3 studies – TOPAZ-1 and TOPAZ-2 – to evaluate litifilimab in SLE over a 52-week period. The company also plans to start a pivotal study of the drug in CLE later this year, according to a press release.

Six coauthors are employees of Biogen; five, including Dr. Furie, reported serving as a consultant to the company; one served on a data and safety monitoring board for Biogen; and Dr. Salmon owns stock in the company.

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

Treatment with the humanized monoclonal antibody litifilimab for patients with systemic lupus erythematosus (SLE) led to greater improvements in joint manifestations than did placebo in an international phase 2 trial that reflects keen interest in targeting type 1 interferon and the innate immune system.

Litifilimab was associated with an approximately three-joint reduction in the number of swollen and tender joints, compared with placebo, over 24 weeks in the study, which was published  in The New England Journal of Medicine.

The study was the first part of the LILAC trial, a two-part, phase 2 study. The second part involved cutaneous lupus erythematosus (CLE) with or without systemic manifestations. Treatment led to improvements in skin disease, as measured by Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores. It was published  in the New England Journal of Medicine.

The investigational drug targets blood dendritic cell antigen 2 (BDCA2). The antigen is expressed solely on plasmacytoid dendritic cells (pDCs), which accumulate in skin lesions and organs of patients with SLE. When the antibody binds to BDCA2, “the synthesis of a variety of cytokines is shut down – type 1 interferons, type 3 interferons, TNF [tumor necrosis factor], and [other cytokines and chemokines] made by the pDCs,” Richard A. Furie, MD, lead author of the article, said in an interview.

In a phase 1 trial involving patients with SLE and CLE, the drug’s biologic activity was shown by a dampened interferon signature in blood and modulated type 1 interferon-induced proteins in the skin, he and his coinvestigators noted.

Dr. Furie is chief of rheumatology at Northwell Health and professor of medicine at the Feinstein Institutes for Medical Research at Northwell and at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York.
 

Impact on the joints

The primary analysis in the SLE trial involved 102 patients who had SLE, arthritis, and active skin disease. The patients received litifilimab 450 mg or placebo, administered subcutaneously, at weeks 0, 2, 4, 8, 12, 16, and 20. The patients were required to have at least four tender joints and at least four swollen joints, and these active joints had to be those classically involved in lupus arthritis.

The mean (± standard deviation) baseline number of active joints was 19 ± 8.4 in the litifilimab group and 21.6 ± 8.5 in placebo group. From baseline to week 24, the least-squares mean (± standard deviation) change in the total number of active joints was –15.0 ± 1.2 with litifilimab and –11.6 ± 1.3 with placebo (mean difference, –3.4; 95% confidence interval, –6.7 to -0.2; P = .04).

Most of the secondary endpoints did not support the results of the primary analysis. However, improvement was seen in the SLE Responder Index (SRI-4) – a three-component global index that Dr. Furie and others developed in 2009 using data from the phase 2 SLE trial of belimumab (Benlysta).

The composite index, used in the phase 3 trial of belimumab, captures improvement in disease activity without a worsening of the condition overall or new significant disease activity in other domains. “It’s a dichotomous measure – either you’re a responder or not,” Dr. Furie said in the interview.

Response on the SRI-4 was defined as a reduction of at least 4 points from baseline in the SLEDAI-2K score (the Systemic Lupus Erythematosus Disease Activity Index), no new disease activity as measured by one score of A (severe) or more than one score of B (moderate) on the BILAG (British Isles Lupus Assessment Group) index, and no increase of 0.3 points or more on the Physician’s Global Assessment.

A total of 56% of the patients in the litifilimab group showed responses on the SRI-4 at week 24, compared with 29% in the placebo group (least-squares mean difference, 26.4%; 95% confidence interval [CI], 9.5-43.2). This is “a robust response” that is much greater than the effect size seen in the phase 3 trial of belimumab or in research on anifrolumab (Saphnelo). Both of those drugs are approved for SLE, Dr. Furie said. “We’ll need to see if it’s reproduced in phase 3.”

There’s “little question that litifilimab works for the skin,” Dr. Furie noted. In the second part of the LILAC study, which focused on CLE, litifilimab demonstrated efficacy, and the SLE trial lends more support. Among several secondary endpoints evaluating skin-related disease activity, a reduction of at least 7 points from baseline in the CLASI-A score (a clinically relevant threshold) occurred in 56% of the litifilimab group and 34% of the placebo group.

The trial was conducted at 55 centers in Asia, Europe, Latin America, and the United States. The SLE part of the study began as a dose-ranging study aimed at evaluating cutaneous lupus activity, but owing to “slow enrollment and to allow an assessment of the effect of litifilimab on arthritis in SLE,” the protocol and primary endpoint were amended before the trial data were unblinded to evaluate only the 450-mg dose among participants with active arthritis and skin disease (at least one active skin lesion), the investigators explained.

Background therapy for SLE was allowed if the therapy was initiated at least 12 weeks before randomization and if dose levels were stable through the trial period. Glucocorticoids had to be tapered to ≤ 10 mg/day according to a specified regimen.

Making progress for lupus

Jane E. Salmon, MD, director of the Lupus and APS Center of Excellence and codirector of the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery in New York, who was not involved in the research, said in an email that she is “cautiously optimistic, because in SLE, successful phase 2 trials too often are followed by unsuccessful phase 3 trials.”

Courtesy Hospital for Special Surgery

Blocking the production of type 1 interferon by pDCs implicated in SLE pathogenesis has the theoretical advantage of preserving type 1 interferon critical to protection from viruses, she noted. Herpes infections were reported among patients who received litifilimab, but rates were not increased, compared with placebo.

Diversity is an important priority in further research, Dr. Salmon said.

Daniel J. Wallace, MD, of Cedars-Sinai Medical Center in Los Angeles, similarly pointed out in an editorial that accompanied the SLE phase 2 trial that while Black patients make up one-third of the U.S. population with lupus, only about 10% of study participants whose race and ethnicity was reported were Black). (Race was not reported by sites in Europe.)

The results of the LILAC trials “encourage further exploration of interventions that affect upstream lupus inflammatory pathways in the innate immune system in lupus,” Dr. Wallace wrote. He noted that lupus has “lagged behind its rheumatic cousins,” such as rheumatoid arthritis and vasculitis, in drug development.

Developing endpoints and study designs for SLE trials has been challenging, at least partly because it is a multisystem disease, Dr. Furie said. “But we’re making progress.”

Anifrolumab, a type 1 interferon receptor monoclonal antibody that was approved for SLE in July 2021, “may have a broader effect on type 1 interferons,” he noted, while litifilimab “may have a broader effect on proinflammatory cytokines, at least those expressed by pDCs.”

Biogen, the sponsor of the LILAC trial, is currently enrolling patients in phase 3 studies – TOPAZ-1 and TOPAZ-2 – to evaluate litifilimab in SLE over a 52-week period. The company also plans to start a pivotal study of the drug in CLE later this year, according to a press release.

Six coauthors are employees of Biogen; five, including Dr. Furie, reported serving as a consultant to the company; one served on a data and safety monitoring board for Biogen; and Dr. Salmon owns stock in the company.

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

Treatment with the humanized monoclonal antibody litifilimab for patients with systemic lupus erythematosus (SLE) led to greater improvements in joint manifestations than did placebo in an international phase 2 trial that reflects keen interest in targeting type 1 interferon and the innate immune system.

Litifilimab was associated with an approximately three-joint reduction in the number of swollen and tender joints, compared with placebo, over 24 weeks in the study, which was published  in The New England Journal of Medicine.

The study was the first part of the LILAC trial, a two-part, phase 2 study. The second part involved cutaneous lupus erythematosus (CLE) with or without systemic manifestations. Treatment led to improvements in skin disease, as measured by Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores. It was published  in the New England Journal of Medicine.

The investigational drug targets blood dendritic cell antigen 2 (BDCA2). The antigen is expressed solely on plasmacytoid dendritic cells (pDCs), which accumulate in skin lesions and organs of patients with SLE. When the antibody binds to BDCA2, “the synthesis of a variety of cytokines is shut down – type 1 interferons, type 3 interferons, TNF [tumor necrosis factor], and [other cytokines and chemokines] made by the pDCs,” Richard A. Furie, MD, lead author of the article, said in an interview.

In a phase 1 trial involving patients with SLE and CLE, the drug’s biologic activity was shown by a dampened interferon signature in blood and modulated type 1 interferon-induced proteins in the skin, he and his coinvestigators noted.

Dr. Furie is chief of rheumatology at Northwell Health and professor of medicine at the Feinstein Institutes for Medical Research at Northwell and at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York.
 

Impact on the joints

The primary analysis in the SLE trial involved 102 patients who had SLE, arthritis, and active skin disease. The patients received litifilimab 450 mg or placebo, administered subcutaneously, at weeks 0, 2, 4, 8, 12, 16, and 20. The patients were required to have at least four tender joints and at least four swollen joints, and these active joints had to be those classically involved in lupus arthritis.

The mean (± standard deviation) baseline number of active joints was 19 ± 8.4 in the litifilimab group and 21.6 ± 8.5 in placebo group. From baseline to week 24, the least-squares mean (± standard deviation) change in the total number of active joints was –15.0 ± 1.2 with litifilimab and –11.6 ± 1.3 with placebo (mean difference, –3.4; 95% confidence interval, –6.7 to -0.2; P = .04).

Most of the secondary endpoints did not support the results of the primary analysis. However, improvement was seen in the SLE Responder Index (SRI-4) – a three-component global index that Dr. Furie and others developed in 2009 using data from the phase 2 SLE trial of belimumab (Benlysta).

The composite index, used in the phase 3 trial of belimumab, captures improvement in disease activity without a worsening of the condition overall or new significant disease activity in other domains. “It’s a dichotomous measure – either you’re a responder or not,” Dr. Furie said in the interview.

Response on the SRI-4 was defined as a reduction of at least 4 points from baseline in the SLEDAI-2K score (the Systemic Lupus Erythematosus Disease Activity Index), no new disease activity as measured by one score of A (severe) or more than one score of B (moderate) on the BILAG (British Isles Lupus Assessment Group) index, and no increase of 0.3 points or more on the Physician’s Global Assessment.

A total of 56% of the patients in the litifilimab group showed responses on the SRI-4 at week 24, compared with 29% in the placebo group (least-squares mean difference, 26.4%; 95% confidence interval [CI], 9.5-43.2). This is “a robust response” that is much greater than the effect size seen in the phase 3 trial of belimumab or in research on anifrolumab (Saphnelo). Both of those drugs are approved for SLE, Dr. Furie said. “We’ll need to see if it’s reproduced in phase 3.”

There’s “little question that litifilimab works for the skin,” Dr. Furie noted. In the second part of the LILAC study, which focused on CLE, litifilimab demonstrated efficacy, and the SLE trial lends more support. Among several secondary endpoints evaluating skin-related disease activity, a reduction of at least 7 points from baseline in the CLASI-A score (a clinically relevant threshold) occurred in 56% of the litifilimab group and 34% of the placebo group.

The trial was conducted at 55 centers in Asia, Europe, Latin America, and the United States. The SLE part of the study began as a dose-ranging study aimed at evaluating cutaneous lupus activity, but owing to “slow enrollment and to allow an assessment of the effect of litifilimab on arthritis in SLE,” the protocol and primary endpoint were amended before the trial data were unblinded to evaluate only the 450-mg dose among participants with active arthritis and skin disease (at least one active skin lesion), the investigators explained.

Background therapy for SLE was allowed if the therapy was initiated at least 12 weeks before randomization and if dose levels were stable through the trial period. Glucocorticoids had to be tapered to ≤ 10 mg/day according to a specified regimen.

Making progress for lupus

Jane E. Salmon, MD, director of the Lupus and APS Center of Excellence and codirector of the Mary Kirkland Center for Lupus Research at the Hospital for Special Surgery in New York, who was not involved in the research, said in an email that she is “cautiously optimistic, because in SLE, successful phase 2 trials too often are followed by unsuccessful phase 3 trials.”

Courtesy Hospital for Special Surgery

Blocking the production of type 1 interferon by pDCs implicated in SLE pathogenesis has the theoretical advantage of preserving type 1 interferon critical to protection from viruses, she noted. Herpes infections were reported among patients who received litifilimab, but rates were not increased, compared with placebo.

Diversity is an important priority in further research, Dr. Salmon said.

Daniel J. Wallace, MD, of Cedars-Sinai Medical Center in Los Angeles, similarly pointed out in an editorial that accompanied the SLE phase 2 trial that while Black patients make up one-third of the U.S. population with lupus, only about 10% of study participants whose race and ethnicity was reported were Black). (Race was not reported by sites in Europe.)

The results of the LILAC trials “encourage further exploration of interventions that affect upstream lupus inflammatory pathways in the innate immune system in lupus,” Dr. Wallace wrote. He noted that lupus has “lagged behind its rheumatic cousins,” such as rheumatoid arthritis and vasculitis, in drug development.

Developing endpoints and study designs for SLE trials has been challenging, at least partly because it is a multisystem disease, Dr. Furie said. “But we’re making progress.”

Anifrolumab, a type 1 interferon receptor monoclonal antibody that was approved for SLE in July 2021, “may have a broader effect on type 1 interferons,” he noted, while litifilimab “may have a broader effect on proinflammatory cytokines, at least those expressed by pDCs.”

Biogen, the sponsor of the LILAC trial, is currently enrolling patients in phase 3 studies – TOPAZ-1 and TOPAZ-2 – to evaluate litifilimab in SLE over a 52-week period. The company also plans to start a pivotal study of the drug in CLE later this year, according to a press release.

Six coauthors are employees of Biogen; five, including Dr. Furie, reported serving as a consultant to the company; one served on a data and safety monitoring board for Biogen; and Dr. Salmon owns stock in the company.

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

After 8 weeks, eight out of ten people with seborrheic dermatitis saw their symptoms cleared or improved with once-daily treatment with roflumilast 0.3% foam, according to the results of the phase 3 STRATUM trial.

More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
 

Common condition led to rapid recruitment

“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.

“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”

While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.

It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”

Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.  

For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years. 

Multiple improvements seen in ‘happy trial’

The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).

Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.

“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.

A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.

“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.

“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.

The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
 

Lesson for practice: Advise patients to moisturize?

“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.

It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.

“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”

The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.

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

After 8 weeks, eight out of ten people with seborrheic dermatitis saw their symptoms cleared or improved with once-daily treatment with roflumilast 0.3% foam, according to the results of the phase 3 STRATUM trial.

More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
 

Common condition led to rapid recruitment

“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.

“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”

While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.

It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”

Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.  

For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years. 

Multiple improvements seen in ‘happy trial’

The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).

Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.

“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.

A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.

“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.

“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.

The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
 

Lesson for practice: Advise patients to moisturize?

“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.

It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.

“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”

The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.

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

After 8 weeks, eight out of ten people with seborrheic dermatitis saw their symptoms cleared or improved with once-daily treatment with roflumilast 0.3% foam, according to the results of the phase 3 STRATUM trial.

More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
 

Common condition led to rapid recruitment

“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.

“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”

While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.

It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”

Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.  

For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years. 

Multiple improvements seen in ‘happy trial’

The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).

Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.

“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.

A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.

“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.

“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.

The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
 

Lesson for practice: Advise patients to moisturize?

“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.

It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.

“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”

The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.

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

Patients with prurigo nodularis (PN) who had severe itch and high lesion counts and whose condition was inadequately controlled with prior therapies experienced significant improvements with dupilumab (Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.

The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.

More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.

The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.

Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”

Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.

The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.

Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.

He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).

Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).

With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.

Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.

Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.

The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.

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

Patients with prurigo nodularis (PN) who had severe itch and high lesion counts and whose condition was inadequately controlled with prior therapies experienced significant improvements with dupilumab (Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.

The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.

More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.

The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.

Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”

Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.

The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.

Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.

He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).

Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).

With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.

Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.

Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.

The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.

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

Patients with prurigo nodularis (PN) who had severe itch and high lesion counts and whose condition was inadequately controlled with prior therapies experienced significant improvements with dupilumab (Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.

The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.

More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.

The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.

Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”

Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.

The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.

Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.

He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).

Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).

With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.

Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.

Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.

The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.

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

Around half the people who wear face masks may develop acne, facial dermatitis, itch, or pressure injuries, and the risk increases with the length of time the mask is worn, according to a recently published systematic review and meta-analysis.

“This report finds the most statistically significant risk factor for developing a facial dermatosis under a face mask is how long one wears the mask. Specifically, wearing a mask for more than 4 to 6 hours correlated most strongly with the development of a facial skin problem,” Jami L. Miller, MD, associate professor of dermatology, Vanderbilt University Medical Center, Nashville, Tenn., told this news organization. Dr. Miller was not involved in the study.

“The type of mask and the environment were of less significance,” she added.

UerDomwet/PxHere

• The overall prevalence of facial dermatoses was 55%
• Individually, facial dermatitis, itch, acne, and pressure injuries were consistently reported as facial dermatoses, with pooled prevalence rates of 24%, 30%, 31%, and 31%, respectively
• The duration of mask wearing was the most significant risk factor for facial dermatoses (P < .001)
• Respirators, including N95 masks, were not more likely than surgical masks to be linked with facial dermatoses

“Understanding risk factors of mask wearing, including situation, duration, and type of mask, may allow for targeted interventions to mitigate problems,” Dr. Yew told this news organization.

He advised taking a break from mask wearing after 4 to 6 hours to improve outcomes.  

Dr. Yew acknowledged limitations, including that most of the reviewed studies relied on self-reported symptoms.

“Patient factors were not investigated in most studies; therefore, we were not able to ascertain their contributory role in the development of facial dermatoses from mask wearing,” he said. “We were also unable to prove causation between risk factors and outcome.” 

Four dermatologists welcome the findings

Dr. Miller called this an “interesting, and certainly relevant” study, now that mask wearing is common and facial skin problems are fairly common complaints in medical visits.

“As the authors say, irritants or contact allergens with longer exposures can be expected to cause a more severe dermatitis than short contact,” she said. “Longer duration also can cause occlusion of pores and hair follicles, which can be expected to worsen acne and folliculitis.”

“I was surprised that the type of mask did not seem to matter significantly,” she added. “Patients wearing N95 masks may be relieved to know N95s do not cause more skin problems than lighter masks.”

Still, Dr. Miller had several questions, including if the materials and chemical finishes that vary by manufacturer may affect skin conditions.

Olga Bunimovich, MD, assistant professor, department of dermatology, University of Pittsburgh School of Medicine, Pennsylvania, called this study “an excellent step towards characterizing the role masks play in facial dermatoses.”

“The study provides a window into the prevalence of these conditions, as well as some understanding of the factors that may be contributing to it,” Dr. Bunimovich, who was not part of the study, added. But “we can also utilize this information to alter behavior in the work environment, allowing ‘mask-free’ breaks to decrease the risk of facial dermatoses.”

Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University School of Medicine, Cleveland, expected skin problems to be linked with mask wearing but didn’t expect the prevalence to be as high as 55%, which she called “very significant.”

“Mask wearing is an important means to prevent transmission of communicable infections, and the practice will most likely continue,” she said.

“Given the data, it is reasonable to advise patients who are already prone to these specific dermatoses to be proactive,” she added. “Early intervention with proper topical medications, preferably prescribed by a dermatologist or other health care provider, and changing masks frequently before they get soaked with moisture, will hopefully lessen the severity of skin rashes and minimize the negative impact on quality of life.”

Also commenting on the study, Susan Massick, MD, dermatologist and clinical associate professor of internal medicine, The Ohio State University Wexner Medical Center, Westerville, said in an interview that she urges people to wear masks, despite these risks.

“The majority of concerns are straightforward, manageable, and overall benign,” she said. “We have a multitude of treatments that can help control, address, or improve symptoms.”

“Masks are an effective and easy way to protect yourself from infection, and they remain one of the most reliable preventions we have,” Dr. Massick noted. “The findings in this article should not preclude anyone from wearing a mask, nor should facial dermatoses be a cause for people to stop wearing their masks.”

The study received no funding. The authors, as well as Dr. Baron, Dr. Miller, Dr. Bunimovich, and Dr. Massick, who were not involved in the study, reported no relevant financial relationships. All experts commented by email.

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

Correction, 9/22/22: An earlier version of this article misstated the name of Dr. Yik Weng Yew.

Around half the people who wear face masks may develop acne, facial dermatitis, itch, or pressure injuries, and the risk increases with the length of time the mask is worn, according to a recently published systematic review and meta-analysis.

“This report finds the most statistically significant risk factor for developing a facial dermatosis under a face mask is how long one wears the mask. Specifically, wearing a mask for more than 4 to 6 hours correlated most strongly with the development of a facial skin problem,” Jami L. Miller, MD, associate professor of dermatology, Vanderbilt University Medical Center, Nashville, Tenn., told this news organization. Dr. Miller was not involved in the study.

“The type of mask and the environment were of less significance,” she added.

UerDomwet/PxHere

• The overall prevalence of facial dermatoses was 55%
• Individually, facial dermatitis, itch, acne, and pressure injuries were consistently reported as facial dermatoses, with pooled prevalence rates of 24%, 30%, 31%, and 31%, respectively
• The duration of mask wearing was the most significant risk factor for facial dermatoses (P < .001)
• Respirators, including N95 masks, were not more likely than surgical masks to be linked with facial dermatoses

“Understanding risk factors of mask wearing, including situation, duration, and type of mask, may allow for targeted interventions to mitigate problems,” Dr. Yew told this news organization.

He advised taking a break from mask wearing after 4 to 6 hours to improve outcomes.  

Dr. Yew acknowledged limitations, including that most of the reviewed studies relied on self-reported symptoms.

“Patient factors were not investigated in most studies; therefore, we were not able to ascertain their contributory role in the development of facial dermatoses from mask wearing,” he said. “We were also unable to prove causation between risk factors and outcome.” 

Four dermatologists welcome the findings

Dr. Miller called this an “interesting, and certainly relevant” study, now that mask wearing is common and facial skin problems are fairly common complaints in medical visits.

“As the authors say, irritants or contact allergens with longer exposures can be expected to cause a more severe dermatitis than short contact,” she said. “Longer duration also can cause occlusion of pores and hair follicles, which can be expected to worsen acne and folliculitis.”

“I was surprised that the type of mask did not seem to matter significantly,” she added. “Patients wearing N95 masks may be relieved to know N95s do not cause more skin problems than lighter masks.”

Still, Dr. Miller had several questions, including if the materials and chemical finishes that vary by manufacturer may affect skin conditions.

Olga Bunimovich, MD, assistant professor, department of dermatology, University of Pittsburgh School of Medicine, Pennsylvania, called this study “an excellent step towards characterizing the role masks play in facial dermatoses.”

“The study provides a window into the prevalence of these conditions, as well as some understanding of the factors that may be contributing to it,” Dr. Bunimovich, who was not part of the study, added. But “we can also utilize this information to alter behavior in the work environment, allowing ‘mask-free’ breaks to decrease the risk of facial dermatoses.”

Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University School of Medicine, Cleveland, expected skin problems to be linked with mask wearing but didn’t expect the prevalence to be as high as 55%, which she called “very significant.”

“Mask wearing is an important means to prevent transmission of communicable infections, and the practice will most likely continue,” she said.

“Given the data, it is reasonable to advise patients who are already prone to these specific dermatoses to be proactive,” she added. “Early intervention with proper topical medications, preferably prescribed by a dermatologist or other health care provider, and changing masks frequently before they get soaked with moisture, will hopefully lessen the severity of skin rashes and minimize the negative impact on quality of life.”

Also commenting on the study, Susan Massick, MD, dermatologist and clinical associate professor of internal medicine, The Ohio State University Wexner Medical Center, Westerville, said in an interview that she urges people to wear masks, despite these risks.

“The majority of concerns are straightforward, manageable, and overall benign,” she said. “We have a multitude of treatments that can help control, address, or improve symptoms.”

“Masks are an effective and easy way to protect yourself from infection, and they remain one of the most reliable preventions we have,” Dr. Massick noted. “The findings in this article should not preclude anyone from wearing a mask, nor should facial dermatoses be a cause for people to stop wearing their masks.”

The study received no funding. The authors, as well as Dr. Baron, Dr. Miller, Dr. Bunimovich, and Dr. Massick, who were not involved in the study, reported no relevant financial relationships. All experts commented by email.

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

Correction, 9/22/22: An earlier version of this article misstated the name of Dr. Yik Weng Yew.

Around half the people who wear face masks may develop acne, facial dermatitis, itch, or pressure injuries, and the risk increases with the length of time the mask is worn, according to a recently published systematic review and meta-analysis.

“This report finds the most statistically significant risk factor for developing a facial dermatosis under a face mask is how long one wears the mask. Specifically, wearing a mask for more than 4 to 6 hours correlated most strongly with the development of a facial skin problem,” Jami L. Miller, MD, associate professor of dermatology, Vanderbilt University Medical Center, Nashville, Tenn., told this news organization. Dr. Miller was not involved in the study.

“The type of mask and the environment were of less significance,” she added.

UerDomwet/PxHere

• The overall prevalence of facial dermatoses was 55%
• Individually, facial dermatitis, itch, acne, and pressure injuries were consistently reported as facial dermatoses, with pooled prevalence rates of 24%, 30%, 31%, and 31%, respectively
• The duration of mask wearing was the most significant risk factor for facial dermatoses (P < .001)
• Respirators, including N95 masks, were not more likely than surgical masks to be linked with facial dermatoses

“Understanding risk factors of mask wearing, including situation, duration, and type of mask, may allow for targeted interventions to mitigate problems,” Dr. Yew told this news organization.

He advised taking a break from mask wearing after 4 to 6 hours to improve outcomes.  

Dr. Yew acknowledged limitations, including that most of the reviewed studies relied on self-reported symptoms.

“Patient factors were not investigated in most studies; therefore, we were not able to ascertain their contributory role in the development of facial dermatoses from mask wearing,” he said. “We were also unable to prove causation between risk factors and outcome.” 

Four dermatologists welcome the findings

Dr. Miller called this an “interesting, and certainly relevant” study, now that mask wearing is common and facial skin problems are fairly common complaints in medical visits.

“As the authors say, irritants or contact allergens with longer exposures can be expected to cause a more severe dermatitis than short contact,” she said. “Longer duration also can cause occlusion of pores and hair follicles, which can be expected to worsen acne and folliculitis.”

“I was surprised that the type of mask did not seem to matter significantly,” she added. “Patients wearing N95 masks may be relieved to know N95s do not cause more skin problems than lighter masks.”

Still, Dr. Miller had several questions, including if the materials and chemical finishes that vary by manufacturer may affect skin conditions.

Olga Bunimovich, MD, assistant professor, department of dermatology, University of Pittsburgh School of Medicine, Pennsylvania, called this study “an excellent step towards characterizing the role masks play in facial dermatoses.”

“The study provides a window into the prevalence of these conditions, as well as some understanding of the factors that may be contributing to it,” Dr. Bunimovich, who was not part of the study, added. But “we can also utilize this information to alter behavior in the work environment, allowing ‘mask-free’ breaks to decrease the risk of facial dermatoses.”

Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University School of Medicine, Cleveland, expected skin problems to be linked with mask wearing but didn’t expect the prevalence to be as high as 55%, which she called “very significant.”

“Mask wearing is an important means to prevent transmission of communicable infections, and the practice will most likely continue,” she said.

“Given the data, it is reasonable to advise patients who are already prone to these specific dermatoses to be proactive,” she added. “Early intervention with proper topical medications, preferably prescribed by a dermatologist or other health care provider, and changing masks frequently before they get soaked with moisture, will hopefully lessen the severity of skin rashes and minimize the negative impact on quality of life.”

Also commenting on the study, Susan Massick, MD, dermatologist and clinical associate professor of internal medicine, The Ohio State University Wexner Medical Center, Westerville, said in an interview that she urges people to wear masks, despite these risks.

“The majority of concerns are straightforward, manageable, and overall benign,” she said. “We have a multitude of treatments that can help control, address, or improve symptoms.”

“Masks are an effective and easy way to protect yourself from infection, and they remain one of the most reliable preventions we have,” Dr. Massick noted. “The findings in this article should not preclude anyone from wearing a mask, nor should facial dermatoses be a cause for people to stop wearing their masks.”

The study received no funding. The authors, as well as Dr. Baron, Dr. Miller, Dr. Bunimovich, and Dr. Massick, who were not involved in the study, reported no relevant financial relationships. All experts commented by email.

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

Correction, 9/22/22: An earlier version of this article misstated the name of Dr. Yik Weng Yew.

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the Food and Drug Administration for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, the manufacturer announced on Sept. 9.

Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.

It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.

FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.

In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.

At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.

In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).

Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.

Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).

Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.

The prescribing information and patient medication guide are available online.

The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.

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

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the Food and Drug Administration for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, the manufacturer announced on Sept. 9.

Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.

It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.

FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.

In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.

At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.

In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).

Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.

Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).

Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.

The prescribing information and patient medication guide are available online.

The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.

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

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the Food and Drug Administration for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, the manufacturer announced on Sept. 9.

Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.

It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.

FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.

In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.

At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.

In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).

Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.

Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).

Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.

The prescribing information and patient medication guide are available online.

The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.

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

During a medical malpractice trial in New Jersey, jurors waited nearly 4 hours for the physician defendant to show up. When he did arrive, the body-building surgeon was sporting two thick gold chains and a diamond pinky ring, and had the top buttons of his shirt open enough to reveal his chest hair.

“This trial was in a very rural, farming community,” recalls medical liability defense attorney Catherine Flynn, of Flynn Watts LLC, based in Parsippany, N.J. “Many of the jurors were wearing flannel shirts and jeans. The doctor’s wife walked in wearing a five-carat diamond ring and other jewelry.”

Ms. Flynn took the couple aside and asked them to remove the jewelry. She explained that the opulent accessories could damage the jury’s view of the physician. The surgeon and his wife, however, refused to remove their jewelry, she said. They didn’t think it was a big deal.

The case against the surgeon involved intraoperative damage to a patient when the physician inadvertently removed a portion of nerve in the area of the procedure. After repair of the nerve, the patient had a positive result. However, the patient alleged the surgeon’s negligence resulted in permanent damage despite the successful repair.

Jurors ultimately found the physician negligent in the case and awarded the plaintiff $1.2 million. Ms. Flynn believes that physician’s flamboyant attire and arrogant nature tainted the jury’s decision.

“In certain counties in New Jersey, his attire would not have been a problem,” she said. “In this rural, farming county, it was a huge problem. You have to know your audience. There are a lot of other things that come into play in a medical malpractice case, but when it comes to damages in a case, you don’t want to be sending the message that supports what somebody’s bias may already be telling them about a doctor.”

The surgeon appealed the verdict, and the case ultimately settled for a lesser amount, according to Ms. Flynn.

An over-the-top wardrobe is just one way that physicians can negatively influence jurors during legal trials. From subtle facial expressions to sudden outbursts to downright rudeness, attorneys have witnessed countless examples of physicians sabotaging their own trials. Legal experts say the cringeworthy experiences are good reminders that jurors are often judging more than just evidence.  

“The minute you enter the courthouse, jurors or potential jurors are sizing you up,” says health law attorney Michael Clark, of Womble Bond Dickinson (US) LLP, based in Houston. “The same phenomenon occurs in a deposition. Awareness of how you are being assessed at all times, and the image that is needed, is important since a negative impression by jurors can have a detrimental effect on a physician’s case.”
 

Juror: We didn’t like the doctor’s shoes

In another case, attorneys warned a physician defendant against dressing in his signature wardrobe during his trial. Against their advice, the doctor showed up daily to his trial in bright pastel, monochromatic suits with matching Gucci-brand shoes, said medical liability defense attorney Meredith C. Lander, of Kaufman Borgeest & Ryan LLP, based in Connecticut. On the witness stand, the doctor was long-winded and wasn’t “terribly likable,” Ms. Lander said.

However, the evidence weighed in the physician’s favor, and there was strong testimony by defense experts. The physician won the case, Ms. Lander said, but after the verdict, the jury foreperson approached the trial attorney and made some disparaging remarks about the defendant.

“The foreperson said the jury didn’t like the doctor or his ‘Gucci suits and shoes,’ but they believed the experts,” Ms. Lander said.

Disruptive behavior can also harm jurors’ perception of physicians, Ms. Flynn adds. During one instance, a surgeon insisted on sitting next to Ms. Flynn, although she generally requests clients sit in the first row so that jurors are not so focused on their reactions during testimony. The surgeon loudly peppered Ms. Flynn with questions as witnesses testified, prompting a reprimand from the judge.

“The judge admonished the doctor several times and said, ‘Doctor, you’re raising your voice. You’ll get a chance to speak with your attorney during the break,’ ” Ms. Flynn recalled. “The doctor refused to stop talking, and the judge told him in front of the jury to go sit in the back of the courtroom. His reaction was, ‘Why do I have to move?! I need to sit here!’ ”

The surgeon eventually moved to the back of the courtroom and a sheriff’s deputy stood next to him. Testimony continued until a note in the form of a paper airplane landed on the table in front of Ms. Flynn. She carefully crumpled the note and tossed it in the wastebasket. Luckily, this drew a laugh from jurors, she said. 

But things got worse when the surgeon testified. Rather than answer the questions, he interrupted and started telling jurors his own version of events.

“The judge finally said, ‘Doctor, if you don’t listen to your attorney and answer her questions, I’m going to make you get off the stand,’ ” Ms. Flynn said. “That was the most unbelievable, egregious self-sabotage trial moment I’ve ever experienced.”

Fortunately, the physician’s legal case was strong, and the experts who testified drove the defense’s side home, Ms. Flynn said. The surgeon won the case.
 

Attorney: Watch what you say in the elevator

Other, more subtle behaviors – while often unintentional – can also be damaging.

Physicians often let their guard down while outside the courtroom and can unknowingly wind up next to a juror in an elevator or standing in a hallway, said Laura Postilion, a partner at Quintairos, Prieto, Wood & Boyer, P.A., based in Chicago.

“For instance, a doctor is in an elevator and feels that some witness on the stand was lying,” Ms. Postilion said. “They might be very upset about it and start ranting about a witness lying, not realizing there is a juror is in the elevator with you.”

Physicians should also be cautious when speaking on the phone to their family or friends during a trial break.

“At the Daley Center in downtown Chicago, there are these long corridors and long line of windows; a lot of people will stand there during breaks. A doctor may be talking to his or her spouse and saying, ‘Yeah, this juror is sleeping!’ Jurors are [often] looking for drama. They’re looking for somebody letting their guard down. Hearing a doctor speak badly about them would certainly give them a reason to dislike the physician.”

Ms. Postilion warns against talking about jurors in or outside of the courtroom. This includes parking structures, she said.

Physicians can take additional steps to save themselves from negative judgment from jurors, attorneys say. Even before the trial starts, Ms. Postilion advises clients to make their social media accounts private. Some curious jurors may look up a physician’s social media accounts to learn more about their personal life, political leanings, or social beliefs, which could prejudice them against the doctor, she said.

Once on the stand, the words and tone used are key. The last thing a physician defendant wants is to come across as arrogant or condescending to jurors, said medical liability defense attorney Michael Moroney, of Flynn Watts LLC.

“For instance, a defendant might say, ‘Well, let me make this simple for you,’ as if they’re talking to a bunch of schoolchildren,” he said. “You don’t know who’s on the jury. That type of language can be offensive.”

Ms. Lander counsels her clients to refrain from using the common phrase, “honestly,” before answering questions on the stand.

“Everything you’re saying on the stand is presumed to be honest,” she said. “When you start an answer with, ‘Honestly…’ out of habit, it really does undercut everything that follows and everything else that’s already been said. It suggests that you were not being honest in your other answers.”
 

Attitude, body language speak volumes

Keep in mind that plaintiffs’ attorneys will try their best to rattle physicians on the stand and get them to appear unlikeable, says Mr. Clark, the Houston-based health law attorney. Physicians who lose their cool and begin arguing with attorneys play into their strategy.

“Plaintiffs’ attorneys have been trained in ways to get under their skin,” he said. “Righteous indignation and annoyance are best left for a rare occasion. Think about how you feel in a social setting when people are bickering in front of you. It’s uncomfortable at best. That’s how a jury feels too.”

Body language is also important, Mr. Clark notes. Physicians should avoid crossed arms, leaning back and rocking, or putting a hand on their mouth while testifying, he said. Many attorneys have practice sessions with their clients and record the interaction so that doctors can watch it and see how they look.

“Know your strengths and weaknesses,” he said. “Get help from your lawyer and perhaps consultants about how to improve these skills. Practice and preparation are important.”

Ms. Postilion goes over courtroom clothing with physician clients before trial. Anything “too flashy, too high-end, or too dumpy” should be avoided, she said. Getting accustomed to the courtroom and practicing in an empty courtroom are good ways to ensure that a physician’s voice is loud enough and projecting far enough in the courtroom, she adds.

“The doctor should try to be the best version of him- or herself to jurors,” she said. “A jury can pick up someone who’s trying to be something they’re not. A good attorney can help the doctor find the best version of themselves and capitalize on it. What is it that you want the jury to know about your care of the patient? Take that overall feeling and make sure it’s clearly expressed to the jury.”

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

During a medical malpractice trial in New Jersey, jurors waited nearly 4 hours for the physician defendant to show up. When he did arrive, the body-building surgeon was sporting two thick gold chains and a diamond pinky ring, and had the top buttons of his shirt open enough to reveal his chest hair.

“This trial was in a very rural, farming community,” recalls medical liability defense attorney Catherine Flynn, of Flynn Watts LLC, based in Parsippany, N.J. “Many of the jurors were wearing flannel shirts and jeans. The doctor’s wife walked in wearing a five-carat diamond ring and other jewelry.”

Ms. Flynn took the couple aside and asked them to remove the jewelry. She explained that the opulent accessories could damage the jury’s view of the physician. The surgeon and his wife, however, refused to remove their jewelry, she said. They didn’t think it was a big deal.

The case against the surgeon involved intraoperative damage to a patient when the physician inadvertently removed a portion of nerve in the area of the procedure. After repair of the nerve, the patient had a positive result. However, the patient alleged the surgeon’s negligence resulted in permanent damage despite the successful repair.

Jurors ultimately found the physician negligent in the case and awarded the plaintiff $1.2 million. Ms. Flynn believes that physician’s flamboyant attire and arrogant nature tainted the jury’s decision.

“In certain counties in New Jersey, his attire would not have been a problem,” she said. “In this rural, farming county, it was a huge problem. You have to know your audience. There are a lot of other things that come into play in a medical malpractice case, but when it comes to damages in a case, you don’t want to be sending the message that supports what somebody’s bias may already be telling them about a doctor.”

The surgeon appealed the verdict, and the case ultimately settled for a lesser amount, according to Ms. Flynn.

An over-the-top wardrobe is just one way that physicians can negatively influence jurors during legal trials. From subtle facial expressions to sudden outbursts to downright rudeness, attorneys have witnessed countless examples of physicians sabotaging their own trials. Legal experts say the cringeworthy experiences are good reminders that jurors are often judging more than just evidence.  

“The minute you enter the courthouse, jurors or potential jurors are sizing you up,” says health law attorney Michael Clark, of Womble Bond Dickinson (US) LLP, based in Houston. “The same phenomenon occurs in a deposition. Awareness of how you are being assessed at all times, and the image that is needed, is important since a negative impression by jurors can have a detrimental effect on a physician’s case.”
 

Juror: We didn’t like the doctor’s shoes

In another case, attorneys warned a physician defendant against dressing in his signature wardrobe during his trial. Against their advice, the doctor showed up daily to his trial in bright pastel, monochromatic suits with matching Gucci-brand shoes, said medical liability defense attorney Meredith C. Lander, of Kaufman Borgeest & Ryan LLP, based in Connecticut. On the witness stand, the doctor was long-winded and wasn’t “terribly likable,” Ms. Lander said.

However, the evidence weighed in the physician’s favor, and there was strong testimony by defense experts. The physician won the case, Ms. Lander said, but after the verdict, the jury foreperson approached the trial attorney and made some disparaging remarks about the defendant.

“The foreperson said the jury didn’t like the doctor or his ‘Gucci suits and shoes,’ but they believed the experts,” Ms. Lander said.

Disruptive behavior can also harm jurors’ perception of physicians, Ms. Flynn adds. During one instance, a surgeon insisted on sitting next to Ms. Flynn, although she generally requests clients sit in the first row so that jurors are not so focused on their reactions during testimony. The surgeon loudly peppered Ms. Flynn with questions as witnesses testified, prompting a reprimand from the judge.

“The judge admonished the doctor several times and said, ‘Doctor, you’re raising your voice. You’ll get a chance to speak with your attorney during the break,’ ” Ms. Flynn recalled. “The doctor refused to stop talking, and the judge told him in front of the jury to go sit in the back of the courtroom. His reaction was, ‘Why do I have to move?! I need to sit here!’ ”

The surgeon eventually moved to the back of the courtroom and a sheriff’s deputy stood next to him. Testimony continued until a note in the form of a paper airplane landed on the table in front of Ms. Flynn. She carefully crumpled the note and tossed it in the wastebasket. Luckily, this drew a laugh from jurors, she said. 

But things got worse when the surgeon testified. Rather than answer the questions, he interrupted and started telling jurors his own version of events.

“The judge finally said, ‘Doctor, if you don’t listen to your attorney and answer her questions, I’m going to make you get off the stand,’ ” Ms. Flynn said. “That was the most unbelievable, egregious self-sabotage trial moment I’ve ever experienced.”

Fortunately, the physician’s legal case was strong, and the experts who testified drove the defense’s side home, Ms. Flynn said. The surgeon won the case.
 

Attorney: Watch what you say in the elevator

Other, more subtle behaviors – while often unintentional – can also be damaging.

Physicians often let their guard down while outside the courtroom and can unknowingly wind up next to a juror in an elevator or standing in a hallway, said Laura Postilion, a partner at Quintairos, Prieto, Wood & Boyer, P.A., based in Chicago.

“For instance, a doctor is in an elevator and feels that some witness on the stand was lying,” Ms. Postilion said. “They might be very upset about it and start ranting about a witness lying, not realizing there is a juror is in the elevator with you.”

Physicians should also be cautious when speaking on the phone to their family or friends during a trial break.

“At the Daley Center in downtown Chicago, there are these long corridors and long line of windows; a lot of people will stand there during breaks. A doctor may be talking to his or her spouse and saying, ‘Yeah, this juror is sleeping!’ Jurors are [often] looking for drama. They’re looking for somebody letting their guard down. Hearing a doctor speak badly about them would certainly give them a reason to dislike the physician.”

Ms. Postilion warns against talking about jurors in or outside of the courtroom. This includes parking structures, she said.

Physicians can take additional steps to save themselves from negative judgment from jurors, attorneys say. Even before the trial starts, Ms. Postilion advises clients to make their social media accounts private. Some curious jurors may look up a physician’s social media accounts to learn more about their personal life, political leanings, or social beliefs, which could prejudice them against the doctor, she said.

Once on the stand, the words and tone used are key. The last thing a physician defendant wants is to come across as arrogant or condescending to jurors, said medical liability defense attorney Michael Moroney, of Flynn Watts LLC.

“For instance, a defendant might say, ‘Well, let me make this simple for you,’ as if they’re talking to a bunch of schoolchildren,” he said. “You don’t know who’s on the jury. That type of language can be offensive.”

Ms. Lander counsels her clients to refrain from using the common phrase, “honestly,” before answering questions on the stand.

“Everything you’re saying on the stand is presumed to be honest,” she said. “When you start an answer with, ‘Honestly…’ out of habit, it really does undercut everything that follows and everything else that’s already been said. It suggests that you were not being honest in your other answers.”
 

Attitude, body language speak volumes

Keep in mind that plaintiffs’ attorneys will try their best to rattle physicians on the stand and get them to appear unlikeable, says Mr. Clark, the Houston-based health law attorney. Physicians who lose their cool and begin arguing with attorneys play into their strategy.

“Plaintiffs’ attorneys have been trained in ways to get under their skin,” he said. “Righteous indignation and annoyance are best left for a rare occasion. Think about how you feel in a social setting when people are bickering in front of you. It’s uncomfortable at best. That’s how a jury feels too.”

Body language is also important, Mr. Clark notes. Physicians should avoid crossed arms, leaning back and rocking, or putting a hand on their mouth while testifying, he said. Many attorneys have practice sessions with their clients and record the interaction so that doctors can watch it and see how they look.

“Know your strengths and weaknesses,” he said. “Get help from your lawyer and perhaps consultants about how to improve these skills. Practice and preparation are important.”

Ms. Postilion goes over courtroom clothing with physician clients before trial. Anything “too flashy, too high-end, or too dumpy” should be avoided, she said. Getting accustomed to the courtroom and practicing in an empty courtroom are good ways to ensure that a physician’s voice is loud enough and projecting far enough in the courtroom, she adds.

“The doctor should try to be the best version of him- or herself to jurors,” she said. “A jury can pick up someone who’s trying to be something they’re not. A good attorney can help the doctor find the best version of themselves and capitalize on it. What is it that you want the jury to know about your care of the patient? Take that overall feeling and make sure it’s clearly expressed to the jury.”

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

During a medical malpractice trial in New Jersey, jurors waited nearly 4 hours for the physician defendant to show up. When he did arrive, the body-building surgeon was sporting two thick gold chains and a diamond pinky ring, and had the top buttons of his shirt open enough to reveal his chest hair.

“This trial was in a very rural, farming community,” recalls medical liability defense attorney Catherine Flynn, of Flynn Watts LLC, based in Parsippany, N.J. “Many of the jurors were wearing flannel shirts and jeans. The doctor’s wife walked in wearing a five-carat diamond ring and other jewelry.”

Ms. Flynn took the couple aside and asked them to remove the jewelry. She explained that the opulent accessories could damage the jury’s view of the physician. The surgeon and his wife, however, refused to remove their jewelry, she said. They didn’t think it was a big deal.

The case against the surgeon involved intraoperative damage to a patient when the physician inadvertently removed a portion of nerve in the area of the procedure. After repair of the nerve, the patient had a positive result. However, the patient alleged the surgeon’s negligence resulted in permanent damage despite the successful repair.

Jurors ultimately found the physician negligent in the case and awarded the plaintiff $1.2 million. Ms. Flynn believes that physician’s flamboyant attire and arrogant nature tainted the jury’s decision.

“In certain counties in New Jersey, his attire would not have been a problem,” she said. “In this rural, farming county, it was a huge problem. You have to know your audience. There are a lot of other things that come into play in a medical malpractice case, but when it comes to damages in a case, you don’t want to be sending the message that supports what somebody’s bias may already be telling them about a doctor.”

The surgeon appealed the verdict, and the case ultimately settled for a lesser amount, according to Ms. Flynn.

An over-the-top wardrobe is just one way that physicians can negatively influence jurors during legal trials. From subtle facial expressions to sudden outbursts to downright rudeness, attorneys have witnessed countless examples of physicians sabotaging their own trials. Legal experts say the cringeworthy experiences are good reminders that jurors are often judging more than just evidence.  

“The minute you enter the courthouse, jurors or potential jurors are sizing you up,” says health law attorney Michael Clark, of Womble Bond Dickinson (US) LLP, based in Houston. “The same phenomenon occurs in a deposition. Awareness of how you are being assessed at all times, and the image that is needed, is important since a negative impression by jurors can have a detrimental effect on a physician’s case.”
 

Juror: We didn’t like the doctor’s shoes

In another case, attorneys warned a physician defendant against dressing in his signature wardrobe during his trial. Against their advice, the doctor showed up daily to his trial in bright pastel, monochromatic suits with matching Gucci-brand shoes, said medical liability defense attorney Meredith C. Lander, of Kaufman Borgeest & Ryan LLP, based in Connecticut. On the witness stand, the doctor was long-winded and wasn’t “terribly likable,” Ms. Lander said.

However, the evidence weighed in the physician’s favor, and there was strong testimony by defense experts. The physician won the case, Ms. Lander said, but after the verdict, the jury foreperson approached the trial attorney and made some disparaging remarks about the defendant.

“The foreperson said the jury didn’t like the doctor or his ‘Gucci suits and shoes,’ but they believed the experts,” Ms. Lander said.

Disruptive behavior can also harm jurors’ perception of physicians, Ms. Flynn adds. During one instance, a surgeon insisted on sitting next to Ms. Flynn, although she generally requests clients sit in the first row so that jurors are not so focused on their reactions during testimony. The surgeon loudly peppered Ms. Flynn with questions as witnesses testified, prompting a reprimand from the judge.

“The judge admonished the doctor several times and said, ‘Doctor, you’re raising your voice. You’ll get a chance to speak with your attorney during the break,’ ” Ms. Flynn recalled. “The doctor refused to stop talking, and the judge told him in front of the jury to go sit in the back of the courtroom. His reaction was, ‘Why do I have to move?! I need to sit here!’ ”

The surgeon eventually moved to the back of the courtroom and a sheriff’s deputy stood next to him. Testimony continued until a note in the form of a paper airplane landed on the table in front of Ms. Flynn. She carefully crumpled the note and tossed it in the wastebasket. Luckily, this drew a laugh from jurors, she said. 

But things got worse when the surgeon testified. Rather than answer the questions, he interrupted and started telling jurors his own version of events.

“The judge finally said, ‘Doctor, if you don’t listen to your attorney and answer her questions, I’m going to make you get off the stand,’ ” Ms. Flynn said. “That was the most unbelievable, egregious self-sabotage trial moment I’ve ever experienced.”

Fortunately, the physician’s legal case was strong, and the experts who testified drove the defense’s side home, Ms. Flynn said. The surgeon won the case.
 

Attorney: Watch what you say in the elevator

Other, more subtle behaviors – while often unintentional – can also be damaging.

Physicians often let their guard down while outside the courtroom and can unknowingly wind up next to a juror in an elevator or standing in a hallway, said Laura Postilion, a partner at Quintairos, Prieto, Wood & Boyer, P.A., based in Chicago.

“For instance, a doctor is in an elevator and feels that some witness on the stand was lying,” Ms. Postilion said. “They might be very upset about it and start ranting about a witness lying, not realizing there is a juror is in the elevator with you.”

Physicians should also be cautious when speaking on the phone to their family or friends during a trial break.

“At the Daley Center in downtown Chicago, there are these long corridors and long line of windows; a lot of people will stand there during breaks. A doctor may be talking to his or her spouse and saying, ‘Yeah, this juror is sleeping!’ Jurors are [often] looking for drama. They’re looking for somebody letting their guard down. Hearing a doctor speak badly about them would certainly give them a reason to dislike the physician.”

Ms. Postilion warns against talking about jurors in or outside of the courtroom. This includes parking structures, she said.

Physicians can take additional steps to save themselves from negative judgment from jurors, attorneys say. Even before the trial starts, Ms. Postilion advises clients to make their social media accounts private. Some curious jurors may look up a physician’s social media accounts to learn more about their personal life, political leanings, or social beliefs, which could prejudice them against the doctor, she said.

Once on the stand, the words and tone used are key. The last thing a physician defendant wants is to come across as arrogant or condescending to jurors, said medical liability defense attorney Michael Moroney, of Flynn Watts LLC.

“For instance, a defendant might say, ‘Well, let me make this simple for you,’ as if they’re talking to a bunch of schoolchildren,” he said. “You don’t know who’s on the jury. That type of language can be offensive.”

Ms. Lander counsels her clients to refrain from using the common phrase, “honestly,” before answering questions on the stand.

“Everything you’re saying on the stand is presumed to be honest,” she said. “When you start an answer with, ‘Honestly…’ out of habit, it really does undercut everything that follows and everything else that’s already been said. It suggests that you were not being honest in your other answers.”
 

Attitude, body language speak volumes

Keep in mind that plaintiffs’ attorneys will try their best to rattle physicians on the stand and get them to appear unlikeable, says Mr. Clark, the Houston-based health law attorney. Physicians who lose their cool and begin arguing with attorneys play into their strategy.

“Plaintiffs’ attorneys have been trained in ways to get under their skin,” he said. “Righteous indignation and annoyance are best left for a rare occasion. Think about how you feel in a social setting when people are bickering in front of you. It’s uncomfortable at best. That’s how a jury feels too.”

Body language is also important, Mr. Clark notes. Physicians should avoid crossed arms, leaning back and rocking, or putting a hand on their mouth while testifying, he said. Many attorneys have practice sessions with their clients and record the interaction so that doctors can watch it and see how they look.

“Know your strengths and weaknesses,” he said. “Get help from your lawyer and perhaps consultants about how to improve these skills. Practice and preparation are important.”

Ms. Postilion goes over courtroom clothing with physician clients before trial. Anything “too flashy, too high-end, or too dumpy” should be avoided, she said. Getting accustomed to the courtroom and practicing in an empty courtroom are good ways to ensure that a physician’s voice is loud enough and projecting far enough in the courtroom, she adds.

“The doctor should try to be the best version of him- or herself to jurors,” she said. “A jury can pick up someone who’s trying to be something they’re not. A good attorney can help the doctor find the best version of themselves and capitalize on it. What is it that you want the jury to know about your care of the patient? Take that overall feeling and make sure it’s clearly expressed to the jury.”

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

Patients with melanoma who are deficient in vitamin D have significantly worse overall survival than those with higher levels, according to research presented at the annual congress of the European Academy of Dermatology and Venereology.

Whereas the 5-year overall survival was 90% when vitamin D serum levels were above a 10 ng/mL threshold, it was 84% when levels fell below it. Notably, the gap in overall survival between those above and below the threshold appeared to widen as time went on.

The research adds to existing evidence that “vitamin D levels can play an important and independent role in patients’ survival outcomes,” study investigator Inés Gracia-Darder, MD, told this news organization. “The important application in clinical practice would be to know if vitamin D supplementation influences the survival of melanoma patients,” said Dr. Gracia-Darder, a clinical specialist in dermatology at the Hospital Universitari Son Espases, Mallorca, Spain.

Dr. Inés Gracia-Darder

Known association, but not much data

“It is not a new finding,” but there are limited data, especially in melanoma, said Julie De Smedt, MD, of KU Leuven, Belgium, who was asked to comment on the results. Other groups have shown, certainly for cancer in general, that vitamin D can have an effect on overall survival.

“Low levels of vitamin D are associated with the pathological parameters of the melanoma, such as the thickness of the tumor,” Dr. De Smedt said in an interview, indicating that it’s not just overall survival that might be affected.

“So we assume that also has an effect on melanoma-specific survival,” she added.

That assumption, however, is not supported by the data Dr. Gracia-Darder presented, as there was no difference in melanoma-specific survival among the two groups of patients that had been studied.
 

Retrospective cohort analysis

Vitamin D levels had been studied in 264 patients who were included in the retrospective cohort analysis. All had invasive melanomas, and all had been seen at the Hospital Clinic of Barcelona between January 1998 and June 2021. Their mean age was 57 years, and the median follow-up was 6.7 years.

For inclusion, all patients had to have had their vitamin D levels measured after being diagnosed with melanoma; those with a 25-hydroxyvitamin D3 serum level of less than 10 ng/mL were deemed to be vitamin D deficient, whereas those with levels of 10 ng/mL and above were deemed normal or insufficient.

A measurement less than 10 ng/mL is considered vitamin D deficiency, Dr. De Smedt said. “But there is a difference between countries, and there’s also a difference between societies,” noting the cut-off used in the lab where she works is 20 ng/mL. This makes it difficult to compare studies, she said.
 

Independent association with overall survival

Seasonal variation in vitamin D levels were considered as a possible confounding factor, but Dr. Gracia-Darder noted that there was a similar distribution of measurements taken between October to March and April to September.

Univariate and multivariate analyses established vitamin D deficiency as being independently associated with overall survival with hazard ratios of 2.34 and 2.45, respectively.

Other predictive factors were having a higher Breslow index, as well as older age and gender.
 

Time to recommend vitamin D supplementation?

So should patients with melanoma have their vitamin D levels routinely checked? And what about advising them to take vitamin D supplements?

“In our practice, we analyze the vitamin D levels of our patients,” Dr. Gracia-Darder said. Patients are told to limit their exposure to the sun because of their skin cancer, so they are very likely to become vitamin D deficient.

While dietary changes or supplements might be suggested, there’s no real evidence to support upping vitamin D levels to date, so “future prospective studies are needed,” Dr. Gracia-Darder added.

Such studies have already started, including one in Italy, one in Australia, and another study that Dr. De Smedt has been involved with for the past few years.

Called the ViDMe study, it’s a multicenter, randomized, double-blind trial in which patients are being given a high-dose oral vitamin D supplement or placebo once a month for at least 1 year. About 430 patients with a first cutaneous malignant melanoma have been included in the trial, which started in December 2012.

It is hoped that the results will show that the supplementation will have had a protective effect on the risk of relapse and that there will be a correlation between vitamin D levels in the blood and vitamin D receptor immunoreactivity in the tumor.

“The study is still blinded,” Dr. De Smedt said. “We will unblind in the coming months and then at the end of the year, maybe next year, we will have the results.”

The study reported by Dr. Gracia-Darder did not receive any specific funding. Dr. Gracia-Darder disclosed that the melanoma unit where the study was performed receives many grants and funds to carry out research. She reported no other relevant financial relationships. Dr. De Smedt had no relevant financial relationships. The ViDMe study is sponsored by the Universitaire Ziekenhuizen Leuven.

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

Patients with melanoma who are deficient in vitamin D have significantly worse overall survival than those with higher levels, according to research presented at the annual congress of the European Academy of Dermatology and Venereology.

Whereas the 5-year overall survival was 90% when vitamin D serum levels were above a 10 ng/mL threshold, it was 84% when levels fell below it. Notably, the gap in overall survival between those above and below the threshold appeared to widen as time went on.

The research adds to existing evidence that “vitamin D levels can play an important and independent role in patients’ survival outcomes,” study investigator Inés Gracia-Darder, MD, told this news organization. “The important application in clinical practice would be to know if vitamin D supplementation influences the survival of melanoma patients,” said Dr. Gracia-Darder, a clinical specialist in dermatology at the Hospital Universitari Son Espases, Mallorca, Spain.

Dr. Inés Gracia-Darder

Known association, but not much data

“It is not a new finding,” but there are limited data, especially in melanoma, said Julie De Smedt, MD, of KU Leuven, Belgium, who was asked to comment on the results. Other groups have shown, certainly for cancer in general, that vitamin D can have an effect on overall survival.

“Low levels of vitamin D are associated with the pathological parameters of the melanoma, such as the thickness of the tumor,” Dr. De Smedt said in an interview, indicating that it’s not just overall survival that might be affected.

“So we assume that also has an effect on melanoma-specific survival,” she added.

That assumption, however, is not supported by the data Dr. Gracia-Darder presented, as there was no difference in melanoma-specific survival among the two groups of patients that had been studied.
 

Retrospective cohort analysis

Vitamin D levels had been studied in 264 patients who were included in the retrospective cohort analysis. All had invasive melanomas, and all had been seen at the Hospital Clinic of Barcelona between January 1998 and June 2021. Their mean age was 57 years, and the median follow-up was 6.7 years.

For inclusion, all patients had to have had their vitamin D levels measured after being diagnosed with melanoma; those with a 25-hydroxyvitamin D3 serum level of less than 10 ng/mL were deemed to be vitamin D deficient, whereas those with levels of 10 ng/mL and above were deemed normal or insufficient.

A measurement less than 10 ng/mL is considered vitamin D deficiency, Dr. De Smedt said. “But there is a difference between countries, and there’s also a difference between societies,” noting the cut-off used in the lab where she works is 20 ng/mL. This makes it difficult to compare studies, she said.
 

Independent association with overall survival

Seasonal variation in vitamin D levels were considered as a possible confounding factor, but Dr. Gracia-Darder noted that there was a similar distribution of measurements taken between October to March and April to September.

Univariate and multivariate analyses established vitamin D deficiency as being independently associated with overall survival with hazard ratios of 2.34 and 2.45, respectively.

Other predictive factors were having a higher Breslow index, as well as older age and gender.
 

Time to recommend vitamin D supplementation?

So should patients with melanoma have their vitamin D levels routinely checked? And what about advising them to take vitamin D supplements?

“In our practice, we analyze the vitamin D levels of our patients,” Dr. Gracia-Darder said. Patients are told to limit their exposure to the sun because of their skin cancer, so they are very likely to become vitamin D deficient.

While dietary changes or supplements might be suggested, there’s no real evidence to support upping vitamin D levels to date, so “future prospective studies are needed,” Dr. Gracia-Darder added.

Such studies have already started, including one in Italy, one in Australia, and another study that Dr. De Smedt has been involved with for the past few years.

Called the ViDMe study, it’s a multicenter, randomized, double-blind trial in which patients are being given a high-dose oral vitamin D supplement or placebo once a month for at least 1 year. About 430 patients with a first cutaneous malignant melanoma have been included in the trial, which started in December 2012.

It is hoped that the results will show that the supplementation will have had a protective effect on the risk of relapse and that there will be a correlation between vitamin D levels in the blood and vitamin D receptor immunoreactivity in the tumor.

“The study is still blinded,” Dr. De Smedt said. “We will unblind in the coming months and then at the end of the year, maybe next year, we will have the results.”

The study reported by Dr. Gracia-Darder did not receive any specific funding. Dr. Gracia-Darder disclosed that the melanoma unit where the study was performed receives many grants and funds to carry out research. She reported no other relevant financial relationships. Dr. De Smedt had no relevant financial relationships. The ViDMe study is sponsored by the Universitaire Ziekenhuizen Leuven.

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

Patients with melanoma who are deficient in vitamin D have significantly worse overall survival than those with higher levels, according to research presented at the annual congress of the European Academy of Dermatology and Venereology.

Whereas the 5-year overall survival was 90% when vitamin D serum levels were above a 10 ng/mL threshold, it was 84% when levels fell below it. Notably, the gap in overall survival between those above and below the threshold appeared to widen as time went on.

The research adds to existing evidence that “vitamin D levels can play an important and independent role in patients’ survival outcomes,” study investigator Inés Gracia-Darder, MD, told this news organization. “The important application in clinical practice would be to know if vitamin D supplementation influences the survival of melanoma patients,” said Dr. Gracia-Darder, a clinical specialist in dermatology at the Hospital Universitari Son Espases, Mallorca, Spain.

Dr. Inés Gracia-Darder

Known association, but not much data

“It is not a new finding,” but there are limited data, especially in melanoma, said Julie De Smedt, MD, of KU Leuven, Belgium, who was asked to comment on the results. Other groups have shown, certainly for cancer in general, that vitamin D can have an effect on overall survival.

“Low levels of vitamin D are associated with the pathological parameters of the melanoma, such as the thickness of the tumor,” Dr. De Smedt said in an interview, indicating that it’s not just overall survival that might be affected.

“So we assume that also has an effect on melanoma-specific survival,” she added.

That assumption, however, is not supported by the data Dr. Gracia-Darder presented, as there was no difference in melanoma-specific survival among the two groups of patients that had been studied.
 

Retrospective cohort analysis

Vitamin D levels had been studied in 264 patients who were included in the retrospective cohort analysis. All had invasive melanomas, and all had been seen at the Hospital Clinic of Barcelona between January 1998 and June 2021. Their mean age was 57 years, and the median follow-up was 6.7 years.

For inclusion, all patients had to have had their vitamin D levels measured after being diagnosed with melanoma; those with a 25-hydroxyvitamin D3 serum level of less than 10 ng/mL were deemed to be vitamin D deficient, whereas those with levels of 10 ng/mL and above were deemed normal or insufficient.

A measurement less than 10 ng/mL is considered vitamin D deficiency, Dr. De Smedt said. “But there is a difference between countries, and there’s also a difference between societies,” noting the cut-off used in the lab where she works is 20 ng/mL. This makes it difficult to compare studies, she said.
 

Independent association with overall survival

Seasonal variation in vitamin D levels were considered as a possible confounding factor, but Dr. Gracia-Darder noted that there was a similar distribution of measurements taken between October to March and April to September.

Univariate and multivariate analyses established vitamin D deficiency as being independently associated with overall survival with hazard ratios of 2.34 and 2.45, respectively.

Other predictive factors were having a higher Breslow index, as well as older age and gender.
 

Time to recommend vitamin D supplementation?

So should patients with melanoma have their vitamin D levels routinely checked? And what about advising them to take vitamin D supplements?

“In our practice, we analyze the vitamin D levels of our patients,” Dr. Gracia-Darder said. Patients are told to limit their exposure to the sun because of their skin cancer, so they are very likely to become vitamin D deficient.

While dietary changes or supplements might be suggested, there’s no real evidence to support upping vitamin D levels to date, so “future prospective studies are needed,” Dr. Gracia-Darder added.

Such studies have already started, including one in Italy, one in Australia, and another study that Dr. De Smedt has been involved with for the past few years.

Called the ViDMe study, it’s a multicenter, randomized, double-blind trial in which patients are being given a high-dose oral vitamin D supplement or placebo once a month for at least 1 year. About 430 patients with a first cutaneous malignant melanoma have been included in the trial, which started in December 2012.

It is hoped that the results will show that the supplementation will have had a protective effect on the risk of relapse and that there will be a correlation between vitamin D levels in the blood and vitamin D receptor immunoreactivity in the tumor.

“The study is still blinded,” Dr. De Smedt said. “We will unblind in the coming months and then at the end of the year, maybe next year, we will have the results.”

The study reported by Dr. Gracia-Darder did not receive any specific funding. Dr. Gracia-Darder disclosed that the melanoma unit where the study was performed receives many grants and funds to carry out research. She reported no other relevant financial relationships. Dr. De Smedt had no relevant financial relationships. The ViDMe study is sponsored by the Universitaire Ziekenhuizen Leuven.

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

Systemic lupus erythematosus (SLE), or lupus, shows a marked sex bias, affecting about nine females for every one male, according to Susan Kovats, PhD, who studies sex differences in immunity at the Oklahoma Medical Research Foundation in Oklahoma City. This characteristic of lupus suggests that hormones are involved in the pathogenesis of the disease. It also suggests, Dr. Kovats said, that the X chromosome might play a role.

Though studies since the 1970s have indicated a significant role for hormones, the issue is still complex and not well understood, and relatively little research has been done on the molecular mechanisms that might be responsible. This may be because of difficulties with influencing the immune system in vitro, said George A. Robinson, PhD, of University College London’s Centre for Rheumatology.

But Dr. Robinson and his team found a unique way of investigating the role of sex chromosomes and hormones in the inflammatory profiles across subjects of different sex, gender, age, and disease status. In research published online in The Lancet Rheumatology, Dr. Robinson and his team looked at immune cells taken from both cisgender men and women and transgender men and women, and thus were able to “get a more physiological view of what sex hormones are doing to the immune system,” he said.

Dr. Kovats agreed that it was a useful approach. “The transgender people provided an opportunity to effectively separate sex hormone levels from chromosome content,” she said in an interview.
 

Methods and findings

Peripheral blood mononuclear cell (PBMC) samples were taken from cisgender individuals with and without juvenile-onset lupus and assessed for 28 immune-cell subsets, including different T-cell, B-cell, and monotype subsets. Subjects included 39 postpubertal cisgender men and women (17 men and 22 women) who did not have juvenile-onset lupus, and 35 postpubertal cisgender men and women (12 men and 23 women) who did have juvenile onset lupus. All were aged 16-25 years. The transgender group included five transgender men and five transgender women (aged 18-19) who were undergoing gender-affirming sex hormone treatment.

The analysis found that one of the key differences between young postpubertal cisgender men and age-matched cisgender women was that the men had significantly elevated frequencies of regulatory T cells (T-reg cells), and the T-reg cells from young cisgender men had greater suppressive capacity in vitro than did those from cisgender women. In addition, RNA sequencing data from isolated T-reg cells showed the transcriptomic signature of the cisgender men’s T-regs were significantly enriched for genes in the P13K-AKT signaling pathway. The frequency of T-reg cells was not influenced by sex hormones, but their transcriptomic profile was affected.

“These results are beginning to give us an indication of which genes might be differentially regulated by sex hormones and how these are associated with autoimmunity,” Dr. Robinson said. “We’ve also found that, depending on whether you’re a cisgender man or woman, you may have a different pathogenic process to developing lupus. It’s not necessarily that one mechanism drives the disease across both sexes.”
 

New approaches, better insights

Dr. Kovats was particularly impressed by the methods of this study. “It was a natural study, the kind of thing we can usually do only in mice,” she said.

Oklahoma Medical Research Foundation

“One problem with studies on the effects of hormones in disease is that historically researchers have not paid that much attention to the actual hormone levels in the humans they studied. They might look at 100 women and 100 men, roughly between the ages of 20 and 50. We’re starting to see more, but there aren’t a lot of studies correlating numbers of cells in blood with actual hormone levels in the person. And as we know, just because someone’s a certain age doesn’t mean that they have a textbook hormone level. Early menopause, birth-control pills, many things can affect those levels.”

The researchers hope that these findings will shed light on the mechanisms that create sexual bias in autoimmune diseases, particularly lupus, as well as help researchers to better understand the innate and adaptive immunological differences between men and women. It could also be useful in the clinical setting, Dr. Robinson said. Because of the extreme sex bias in lupus, doctors see far more women with the illness than men. When they do see men with lupus, they need to be able to consider how the patient’s sex affects the development and course of the disease. “I think that people need to start looking at patients as clinically different, depending on their sex and gender,” he said. Information like that analyzed in this study could help with that. This could be especially important because as Dr. Kovats pointed out, although men get lupus far less often than women, when they do have it, they tend to have more severe disease.
 

Help from machines

This study was groundbreaking in another area as well. The researchers used machine learning to analyze the data. “We’ve started working a lot more with these analysis methods to try to answer as much as we can with these smaller data sets,” Dr. Robinson said. “Rather than the conventional analysis that we would typically perform, we’re able to use machine learning and artificial intelligence to try and learn from the data and increase the numbers that we’re working with by using a training data set. This allows us to interrogate the data with a lot more precision.”

The authors declared no competing interests.

Systemic lupus erythematosus (SLE), or lupus, shows a marked sex bias, affecting about nine females for every one male, according to Susan Kovats, PhD, who studies sex differences in immunity at the Oklahoma Medical Research Foundation in Oklahoma City. This characteristic of lupus suggests that hormones are involved in the pathogenesis of the disease. It also suggests, Dr. Kovats said, that the X chromosome might play a role.

Though studies since the 1970s have indicated a significant role for hormones, the issue is still complex and not well understood, and relatively little research has been done on the molecular mechanisms that might be responsible. This may be because of difficulties with influencing the immune system in vitro, said George A. Robinson, PhD, of University College London’s Centre for Rheumatology.

But Dr. Robinson and his team found a unique way of investigating the role of sex chromosomes and hormones in the inflammatory profiles across subjects of different sex, gender, age, and disease status. In research published online in The Lancet Rheumatology, Dr. Robinson and his team looked at immune cells taken from both cisgender men and women and transgender men and women, and thus were able to “get a more physiological view of what sex hormones are doing to the immune system,” he said.

Dr. Kovats agreed that it was a useful approach. “The transgender people provided an opportunity to effectively separate sex hormone levels from chromosome content,” she said in an interview.
 

Methods and findings

Peripheral blood mononuclear cell (PBMC) samples were taken from cisgender individuals with and without juvenile-onset lupus and assessed for 28 immune-cell subsets, including different T-cell, B-cell, and monotype subsets. Subjects included 39 postpubertal cisgender men and women (17 men and 22 women) who did not have juvenile-onset lupus, and 35 postpubertal cisgender men and women (12 men and 23 women) who did have juvenile onset lupus. All were aged 16-25 years. The transgender group included five transgender men and five transgender women (aged 18-19) who were undergoing gender-affirming sex hormone treatment.

The analysis found that one of the key differences between young postpubertal cisgender men and age-matched cisgender women was that the men had significantly elevated frequencies of regulatory T cells (T-reg cells), and the T-reg cells from young cisgender men had greater suppressive capacity in vitro than did those from cisgender women. In addition, RNA sequencing data from isolated T-reg cells showed the transcriptomic signature of the cisgender men’s T-regs were significantly enriched for genes in the P13K-AKT signaling pathway. The frequency of T-reg cells was not influenced by sex hormones, but their transcriptomic profile was affected.

“These results are beginning to give us an indication of which genes might be differentially regulated by sex hormones and how these are associated with autoimmunity,” Dr. Robinson said. “We’ve also found that, depending on whether you’re a cisgender man or woman, you may have a different pathogenic process to developing lupus. It’s not necessarily that one mechanism drives the disease across both sexes.”
 

New approaches, better insights

Dr. Kovats was particularly impressed by the methods of this study. “It was a natural study, the kind of thing we can usually do only in mice,” she said.

Oklahoma Medical Research Foundation

“One problem with studies on the effects of hormones in disease is that historically researchers have not paid that much attention to the actual hormone levels in the humans they studied. They might look at 100 women and 100 men, roughly between the ages of 20 and 50. We’re starting to see more, but there aren’t a lot of studies correlating numbers of cells in blood with actual hormone levels in the person. And as we know, just because someone’s a certain age doesn’t mean that they have a textbook hormone level. Early menopause, birth-control pills, many things can affect those levels.”

The researchers hope that these findings will shed light on the mechanisms that create sexual bias in autoimmune diseases, particularly lupus, as well as help researchers to better understand the innate and adaptive immunological differences between men and women. It could also be useful in the clinical setting, Dr. Robinson said. Because of the extreme sex bias in lupus, doctors see far more women with the illness than men. When they do see men with lupus, they need to be able to consider how the patient’s sex affects the development and course of the disease. “I think that people need to start looking at patients as clinically different, depending on their sex and gender,” he said. Information like that analyzed in this study could help with that. This could be especially important because as Dr. Kovats pointed out, although men get lupus far less often than women, when they do have it, they tend to have more severe disease.
 

Help from machines

This study was groundbreaking in another area as well. The researchers used machine learning to analyze the data. “We’ve started working a lot more with these analysis methods to try to answer as much as we can with these smaller data sets,” Dr. Robinson said. “Rather than the conventional analysis that we would typically perform, we’re able to use machine learning and artificial intelligence to try and learn from the data and increase the numbers that we’re working with by using a training data set. This allows us to interrogate the data with a lot more precision.”

The authors declared no competing interests.

Systemic lupus erythematosus (SLE), or lupus, shows a marked sex bias, affecting about nine females for every one male, according to Susan Kovats, PhD, who studies sex differences in immunity at the Oklahoma Medical Research Foundation in Oklahoma City. This characteristic of lupus suggests that hormones are involved in the pathogenesis of the disease. It also suggests, Dr. Kovats said, that the X chromosome might play a role.

Though studies since the 1970s have indicated a significant role for hormones, the issue is still complex and not well understood, and relatively little research has been done on the molecular mechanisms that might be responsible. This may be because of difficulties with influencing the immune system in vitro, said George A. Robinson, PhD, of University College London’s Centre for Rheumatology.

But Dr. Robinson and his team found a unique way of investigating the role of sex chromosomes and hormones in the inflammatory profiles across subjects of different sex, gender, age, and disease status. In research published online in The Lancet Rheumatology, Dr. Robinson and his team looked at immune cells taken from both cisgender men and women and transgender men and women, and thus were able to “get a more physiological view of what sex hormones are doing to the immune system,” he said.

Dr. Kovats agreed that it was a useful approach. “The transgender people provided an opportunity to effectively separate sex hormone levels from chromosome content,” she said in an interview.
 

Methods and findings

Peripheral blood mononuclear cell (PBMC) samples were taken from cisgender individuals with and without juvenile-onset lupus and assessed for 28 immune-cell subsets, including different T-cell, B-cell, and monotype subsets. Subjects included 39 postpubertal cisgender men and women (17 men and 22 women) who did not have juvenile-onset lupus, and 35 postpubertal cisgender men and women (12 men and 23 women) who did have juvenile onset lupus. All were aged 16-25 years. The transgender group included five transgender men and five transgender women (aged 18-19) who were undergoing gender-affirming sex hormone treatment.

The analysis found that one of the key differences between young postpubertal cisgender men and age-matched cisgender women was that the men had significantly elevated frequencies of regulatory T cells (T-reg cells), and the T-reg cells from young cisgender men had greater suppressive capacity in vitro than did those from cisgender women. In addition, RNA sequencing data from isolated T-reg cells showed the transcriptomic signature of the cisgender men’s T-regs were significantly enriched for genes in the P13K-AKT signaling pathway. The frequency of T-reg cells was not influenced by sex hormones, but their transcriptomic profile was affected.

“These results are beginning to give us an indication of which genes might be differentially regulated by sex hormones and how these are associated with autoimmunity,” Dr. Robinson said. “We’ve also found that, depending on whether you’re a cisgender man or woman, you may have a different pathogenic process to developing lupus. It’s not necessarily that one mechanism drives the disease across both sexes.”
 

New approaches, better insights

Dr. Kovats was particularly impressed by the methods of this study. “It was a natural study, the kind of thing we can usually do only in mice,” she said.

Oklahoma Medical Research Foundation

“One problem with studies on the effects of hormones in disease is that historically researchers have not paid that much attention to the actual hormone levels in the humans they studied. They might look at 100 women and 100 men, roughly between the ages of 20 and 50. We’re starting to see more, but there aren’t a lot of studies correlating numbers of cells in blood with actual hormone levels in the person. And as we know, just because someone’s a certain age doesn’t mean that they have a textbook hormone level. Early menopause, birth-control pills, many things can affect those levels.”

The researchers hope that these findings will shed light on the mechanisms that create sexual bias in autoimmune diseases, particularly lupus, as well as help researchers to better understand the innate and adaptive immunological differences between men and women. It could also be useful in the clinical setting, Dr. Robinson said. Because of the extreme sex bias in lupus, doctors see far more women with the illness than men. When they do see men with lupus, they need to be able to consider how the patient’s sex affects the development and course of the disease. “I think that people need to start looking at patients as clinically different, depending on their sex and gender,” he said. Information like that analyzed in this study could help with that. This could be especially important because as Dr. Kovats pointed out, although men get lupus far less often than women, when they do have it, they tend to have more severe disease.
 

Help from machines

This study was groundbreaking in another area as well. The researchers used machine learning to analyze the data. “We’ve started working a lot more with these analysis methods to try to answer as much as we can with these smaller data sets,” Dr. Robinson said. “Rather than the conventional analysis that we would typically perform, we’re able to use machine learning and artificial intelligence to try and learn from the data and increase the numbers that we’re working with by using a training data set. This allows us to interrogate the data with a lot more precision.”

The authors declared no competing interests.