Dermatology News

A dermal-wounding strategy involving fractionated laser resurfacing not only treated actinic keratoses, but it prevented the development of nonmelanoma skin cancer on treated areas, according to the results of a small, randomized trial.

“Previous research suggests a new model to explain why older patients obtain nonmelanoma skin cancer in areas of ongoing sun exposure,” presenting author Jeffrey Wargo, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. “Insulinlike growth factor-1 produced by dermal fibroblasts dictates how overlying skin keratinocytes respond to UVB radiation. The skin of a patient aged in their 20s produces normal levels of healthy fibroblasts, normal levels of insulinlike growth factor 1, and appropriate UVB response via activation of nucleotide excision, repair, and DNA damage checkpoint-signaling systems.”

Older patients, meanwhile, have an increase in senescent fibroblasts, decreased insulinlike growth factor-1 (IGF-1), and an inappropriate UVB response to DNA damage, continued Dr. Wargo, a dermatologist at the Ohio State University Wexner Medical Center in Columbus. Previous studies conducted by his mentor, Jeffrey B. Travers, MD, PhD, a dermatologist and pharmacologist at Wright State University, Dayton, showed that fractionated laser resurfacing (FLR) restores UVB response in older patients’ skin by resulting in new fibroblasts and increased levels of IGF 2 years post wounding.

To determine if FLR of aged skin can prevent the development of actinic keratosis (AK) and nonmelanoma skin cancer, Dr. Travers and Dr. Wargo recruited 48 patients at the Dayton VA Medical Center who were 60 years or older and had at least five AKs on each arm that were 3 mm or smaller, with nothing concerning for skin cancer at the screening visit.

Randomization of which arm was treated was based on an odd or even Social Security Number. That arm was treated with the 2,790 nm Erbium:YSSG ablative laser at 120 J/m² with one pass at 24% coverage from the elbow to hand dorsally. Previously published data reported outcomes for 30 of these patients at 3 and 6 months following treatment. Subsequent to that report, 18 additional subjects have been recruited to the study and follow-up has been extended. Of the 48 patients, 47 were male and their average age was 74, with a range between 61 and 87 years.

At 3 months following FLR, the ratio of AKs on the treated vs. untreated arms was reduced by fourfold, with a P value less than .00001^{, Dr. Wargo reported}. “Throughout the current 30-month follow-up period, this ratio has been maintained,” he said. “In fact, none of the ratios determined at 3, 6, 12, 18, 24, or 30 months post FLR are significantly different. Hence, as described in our first report on this work, these data indicate FLR is an effective treatment for existing AKs. However, our model predicts that FLR treatment will also prevent the occurrence of new AK lesions.”

Among 19 of the study participants who have been followed out to 30 months, untreated arms continued to accumulate increasing number of AKs. In contrast, AKs on treated arms are decreasing with time, indicating the lack of newly initiated lesions.

“A second analysis of the data posits that, if FLR were only removing existing lesions, one would predict the number of AKs that were present at 3 months on both the untreated and FLR-treated [arms] would accumulate at the same rate subsequent to 3 months point in time,” Dr. Wargo said.

He pointed out that 12 patients were removed from the study: two at 12 months, one at 18 months, eight at 24 months, and one at 30 months, as they were found to have 20 or more AKs on their untreated arm and required treatment.

Over the entire study period, “consistent with the notion that FLR was preventing new actinic neoplasia, we noted a dramatic difference in numbers of nonmelanoma skin cancer diagnosed in the untreated areas (22) versus FLR treated areas (2),” Dr. Wargo said. The majority of nonmelanoma skin cancers diagnosed were SCC (17) and 5 basal cell carcinomas on the untreated arms, whereas the 2 diagnosed on the treated arm were SCC. “These studies indicate that a dermal-wounding strategy involving FLR, which upregulates dermal IGF-1 levels, not only treats AKs but prevents nonmelanoma skin cancer,” he said.

The study was funded by the National Institutes of Health. Dr. Travers is the principal investigator. Dr. Wargo reported having no financial disclosures.

dbrunk@mdedge.com

A dermal-wounding strategy involving fractionated laser resurfacing not only treated actinic keratoses, but it prevented the development of nonmelanoma skin cancer on treated areas, according to the results of a small, randomized trial.

“Previous research suggests a new model to explain why older patients obtain nonmelanoma skin cancer in areas of ongoing sun exposure,” presenting author Jeffrey Wargo, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. “Insulinlike growth factor-1 produced by dermal fibroblasts dictates how overlying skin keratinocytes respond to UVB radiation. The skin of a patient aged in their 20s produces normal levels of healthy fibroblasts, normal levels of insulinlike growth factor 1, and appropriate UVB response via activation of nucleotide excision, repair, and DNA damage checkpoint-signaling systems.”

Older patients, meanwhile, have an increase in senescent fibroblasts, decreased insulinlike growth factor-1 (IGF-1), and an inappropriate UVB response to DNA damage, continued Dr. Wargo, a dermatologist at the Ohio State University Wexner Medical Center in Columbus. Previous studies conducted by his mentor, Jeffrey B. Travers, MD, PhD, a dermatologist and pharmacologist at Wright State University, Dayton, showed that fractionated laser resurfacing (FLR) restores UVB response in older patients’ skin by resulting in new fibroblasts and increased levels of IGF 2 years post wounding.

To determine if FLR of aged skin can prevent the development of actinic keratosis (AK) and nonmelanoma skin cancer, Dr. Travers and Dr. Wargo recruited 48 patients at the Dayton VA Medical Center who were 60 years or older and had at least five AKs on each arm that were 3 mm or smaller, with nothing concerning for skin cancer at the screening visit.

Randomization of which arm was treated was based on an odd or even Social Security Number. That arm was treated with the 2,790 nm Erbium:YSSG ablative laser at 120 J/m² with one pass at 24% coverage from the elbow to hand dorsally. Previously published data reported outcomes for 30 of these patients at 3 and 6 months following treatment. Subsequent to that report, 18 additional subjects have been recruited to the study and follow-up has been extended. Of the 48 patients, 47 were male and their average age was 74, with a range between 61 and 87 years.

At 3 months following FLR, the ratio of AKs on the treated vs. untreated arms was reduced by fourfold, with a P value less than .00001^{, Dr. Wargo reported}. “Throughout the current 30-month follow-up period, this ratio has been maintained,” he said. “In fact, none of the ratios determined at 3, 6, 12, 18, 24, or 30 months post FLR are significantly different. Hence, as described in our first report on this work, these data indicate FLR is an effective treatment for existing AKs. However, our model predicts that FLR treatment will also prevent the occurrence of new AK lesions.”

Among 19 of the study participants who have been followed out to 30 months, untreated arms continued to accumulate increasing number of AKs. In contrast, AKs on treated arms are decreasing with time, indicating the lack of newly initiated lesions.

“A second analysis of the data posits that, if FLR were only removing existing lesions, one would predict the number of AKs that were present at 3 months on both the untreated and FLR-treated [arms] would accumulate at the same rate subsequent to 3 months point in time,” Dr. Wargo said.

He pointed out that 12 patients were removed from the study: two at 12 months, one at 18 months, eight at 24 months, and one at 30 months, as they were found to have 20 or more AKs on their untreated arm and required treatment.

Over the entire study period, “consistent with the notion that FLR was preventing new actinic neoplasia, we noted a dramatic difference in numbers of nonmelanoma skin cancer diagnosed in the untreated areas (22) versus FLR treated areas (2),” Dr. Wargo said. The majority of nonmelanoma skin cancers diagnosed were SCC (17) and 5 basal cell carcinomas on the untreated arms, whereas the 2 diagnosed on the treated arm were SCC. “These studies indicate that a dermal-wounding strategy involving FLR, which upregulates dermal IGF-1 levels, not only treats AKs but prevents nonmelanoma skin cancer,” he said.

The study was funded by the National Institutes of Health. Dr. Travers is the principal investigator. Dr. Wargo reported having no financial disclosures.

dbrunk@mdedge.com

A dermal-wounding strategy involving fractionated laser resurfacing not only treated actinic keratoses, but it prevented the development of nonmelanoma skin cancer on treated areas, according to the results of a small, randomized trial.

“Previous research suggests a new model to explain why older patients obtain nonmelanoma skin cancer in areas of ongoing sun exposure,” presenting author Jeffrey Wargo, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. “Insulinlike growth factor-1 produced by dermal fibroblasts dictates how overlying skin keratinocytes respond to UVB radiation. The skin of a patient aged in their 20s produces normal levels of healthy fibroblasts, normal levels of insulinlike growth factor 1, and appropriate UVB response via activation of nucleotide excision, repair, and DNA damage checkpoint-signaling systems.”

Older patients, meanwhile, have an increase in senescent fibroblasts, decreased insulinlike growth factor-1 (IGF-1), and an inappropriate UVB response to DNA damage, continued Dr. Wargo, a dermatologist at the Ohio State University Wexner Medical Center in Columbus. Previous studies conducted by his mentor, Jeffrey B. Travers, MD, PhD, a dermatologist and pharmacologist at Wright State University, Dayton, showed that fractionated laser resurfacing (FLR) restores UVB response in older patients’ skin by resulting in new fibroblasts and increased levels of IGF 2 years post wounding.

To determine if FLR of aged skin can prevent the development of actinic keratosis (AK) and nonmelanoma skin cancer, Dr. Travers and Dr. Wargo recruited 48 patients at the Dayton VA Medical Center who were 60 years or older and had at least five AKs on each arm that were 3 mm or smaller, with nothing concerning for skin cancer at the screening visit.

Randomization of which arm was treated was based on an odd or even Social Security Number. That arm was treated with the 2,790 nm Erbium:YSSG ablative laser at 120 J/m² with one pass at 24% coverage from the elbow to hand dorsally. Previously published data reported outcomes for 30 of these patients at 3 and 6 months following treatment. Subsequent to that report, 18 additional subjects have been recruited to the study and follow-up has been extended. Of the 48 patients, 47 were male and their average age was 74, with a range between 61 and 87 years.

At 3 months following FLR, the ratio of AKs on the treated vs. untreated arms was reduced by fourfold, with a P value less than .00001^{, Dr. Wargo reported}. “Throughout the current 30-month follow-up period, this ratio has been maintained,” he said. “In fact, none of the ratios determined at 3, 6, 12, 18, 24, or 30 months post FLR are significantly different. Hence, as described in our first report on this work, these data indicate FLR is an effective treatment for existing AKs. However, our model predicts that FLR treatment will also prevent the occurrence of new AK lesions.”

Among 19 of the study participants who have been followed out to 30 months, untreated arms continued to accumulate increasing number of AKs. In contrast, AKs on treated arms are decreasing with time, indicating the lack of newly initiated lesions.

“A second analysis of the data posits that, if FLR were only removing existing lesions, one would predict the number of AKs that were present at 3 months on both the untreated and FLR-treated [arms] would accumulate at the same rate subsequent to 3 months point in time,” Dr. Wargo said.

He pointed out that 12 patients were removed from the study: two at 12 months, one at 18 months, eight at 24 months, and one at 30 months, as they were found to have 20 or more AKs on their untreated arm and required treatment.

Over the entire study period, “consistent with the notion that FLR was preventing new actinic neoplasia, we noted a dramatic difference in numbers of nonmelanoma skin cancer diagnosed in the untreated areas (22) versus FLR treated areas (2),” Dr. Wargo said. The majority of nonmelanoma skin cancers diagnosed were SCC (17) and 5 basal cell carcinomas on the untreated arms, whereas the 2 diagnosed on the treated arm were SCC. “These studies indicate that a dermal-wounding strategy involving FLR, which upregulates dermal IGF-1 levels, not only treats AKs but prevents nonmelanoma skin cancer,” he said.

The study was funded by the National Institutes of Health. Dr. Travers is the principal investigator. Dr. Wargo reported having no financial disclosures.

dbrunk@mdedge.com

One year after a single treatment of cellulite with the Rapid Acoustic Pulse (RAP) device, 42 out of 43 patients said that they felt good about the results, an interim analysis from a multicenter study showed.

Iuliia Mikhalitskaia/Getty Images

“I think this speaks to the duration of improvement” associated with this treatment, lead study author Elizabeth L. Tanzi, MD, said during the annual conference of the American Society for Laser Medicine and Surgery.

The study is an extension of a prospective pivotal clinical trial that Dr. Tanzi first presented during late-breaking abstract session at the 2020 virtual annual meeting of the American Academy of Dermatology. For the trial, she and her colleagues at four sites evaluated the safety and effectiveness of the RAP device in 62 women who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. In February 2021, the Food and Drug Administration cleared the device for the short-term improvement in the appearance of cellulite.

“The high peak pressure and fast repetition rate of this device will exploit the viscoelastic tissue compared to other acoustic wave devices that are on the market,” said Dr. Tanzi, associate clinical professor of dermatology at George Washington University, Washington. “Those compressed pulses from electronic filtering and reflector shape eliminate cavitation, heat, and pain. So, what we see physically is fiber septa disruption, as well as other nonthermal physical effects.”

She and her colleagues used a specific photography and fixed lighting setup to record the treated areas at baseline, 12 weeks, and 52 weeks, and administered a patient satisfaction questionnaire at 12 and 52 weeks. Prior to treatment, the investigators marked the dimples and ridges intended for treatment. After placing a hydrogel dressing, it took 45-60 minutes to treat both buttocks and thighs with the RAP device. “It was completely noninvasive,” said Dr. Tanzi, who practices in Chevy Chase, Md. “There was no anesthesia used: no incisions and no needles.”

Among 57 patients who were evaluated at 12 weeks, the pain score on a scale of 0-10 was 2.4, while 61.5% strongly agreed and 35.9% agreed that their cellulite appeared improved. In addition, three blinded assessors were able to correctly identify the treated thigh 96% of the time and physician-graded Global Aesthetic Improvement Scale assessments showed 90% improvement of cellulite.

Follow-up analysis

For the current subject satisfaction analysis, the investigators evaluated results from 43 patients in the trial who were followed for at least 52 weeks (a mean of 60 weeks). Of the 43 patients, 30 (69.8%) strongly agreed and 13 (30.2%) agreed that their cellulite “appears improved.” In addition, 29 (67.4%) strongly agreed, 13 (30.2%) agreed, and 1 (2.3%) disagreed with the statement “I feel there is good improvement” of their cellulite.

“Currently, we are evaluating the blinded assessors’ view of these patients and not just going with [findings from] the patient satisfaction survey, but I think these are encouraging results,” Dr. Tanzi said. “We found that 42 out of 43 patients said, ‘yes; I feel that there was good improvement of the area at 52 weeks.’ ”

Dr. Tanzi disclosed that she is a member of the speakers bureau for Eucerin. She is a member of the advisory board for Allergan, Endo Pharmaceuticals, Pulse Biosciences, Sciton, and Soliton. Soliton markets the RAP device.

dbrunk@mdedge.com

One year after a single treatment of cellulite with the Rapid Acoustic Pulse (RAP) device, 42 out of 43 patients said that they felt good about the results, an interim analysis from a multicenter study showed.

Iuliia Mikhalitskaia/Getty Images

“I think this speaks to the duration of improvement” associated with this treatment, lead study author Elizabeth L. Tanzi, MD, said during the annual conference of the American Society for Laser Medicine and Surgery.

The study is an extension of a prospective pivotal clinical trial that Dr. Tanzi first presented during late-breaking abstract session at the 2020 virtual annual meeting of the American Academy of Dermatology. For the trial, she and her colleagues at four sites evaluated the safety and effectiveness of the RAP device in 62 women who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. In February 2021, the Food and Drug Administration cleared the device for the short-term improvement in the appearance of cellulite.

“The high peak pressure and fast repetition rate of this device will exploit the viscoelastic tissue compared to other acoustic wave devices that are on the market,” said Dr. Tanzi, associate clinical professor of dermatology at George Washington University, Washington. “Those compressed pulses from electronic filtering and reflector shape eliminate cavitation, heat, and pain. So, what we see physically is fiber septa disruption, as well as other nonthermal physical effects.”

She and her colleagues used a specific photography and fixed lighting setup to record the treated areas at baseline, 12 weeks, and 52 weeks, and administered a patient satisfaction questionnaire at 12 and 52 weeks. Prior to treatment, the investigators marked the dimples and ridges intended for treatment. After placing a hydrogel dressing, it took 45-60 minutes to treat both buttocks and thighs with the RAP device. “It was completely noninvasive,” said Dr. Tanzi, who practices in Chevy Chase, Md. “There was no anesthesia used: no incisions and no needles.”

Among 57 patients who were evaluated at 12 weeks, the pain score on a scale of 0-10 was 2.4, while 61.5% strongly agreed and 35.9% agreed that their cellulite appeared improved. In addition, three blinded assessors were able to correctly identify the treated thigh 96% of the time and physician-graded Global Aesthetic Improvement Scale assessments showed 90% improvement of cellulite.

Follow-up analysis

For the current subject satisfaction analysis, the investigators evaluated results from 43 patients in the trial who were followed for at least 52 weeks (a mean of 60 weeks). Of the 43 patients, 30 (69.8%) strongly agreed and 13 (30.2%) agreed that their cellulite “appears improved.” In addition, 29 (67.4%) strongly agreed, 13 (30.2%) agreed, and 1 (2.3%) disagreed with the statement “I feel there is good improvement” of their cellulite.

“Currently, we are evaluating the blinded assessors’ view of these patients and not just going with [findings from] the patient satisfaction survey, but I think these are encouraging results,” Dr. Tanzi said. “We found that 42 out of 43 patients said, ‘yes; I feel that there was good improvement of the area at 52 weeks.’ ”

Dr. Tanzi disclosed that she is a member of the speakers bureau for Eucerin. She is a member of the advisory board for Allergan, Endo Pharmaceuticals, Pulse Biosciences, Sciton, and Soliton. Soliton markets the RAP device.

dbrunk@mdedge.com

One year after a single treatment of cellulite with the Rapid Acoustic Pulse (RAP) device, 42 out of 43 patients said that they felt good about the results, an interim analysis from a multicenter study showed.

Iuliia Mikhalitskaia/Getty Images

“I think this speaks to the duration of improvement” associated with this treatment, lead study author Elizabeth L. Tanzi, MD, said during the annual conference of the American Society for Laser Medicine and Surgery.

The study is an extension of a prospective pivotal clinical trial that Dr. Tanzi first presented during late-breaking abstract session at the 2020 virtual annual meeting of the American Academy of Dermatology. For the trial, she and her colleagues at four sites evaluated the safety and effectiveness of the RAP device in 62 women who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. In February 2021, the Food and Drug Administration cleared the device for the short-term improvement in the appearance of cellulite.

“The high peak pressure and fast repetition rate of this device will exploit the viscoelastic tissue compared to other acoustic wave devices that are on the market,” said Dr. Tanzi, associate clinical professor of dermatology at George Washington University, Washington. “Those compressed pulses from electronic filtering and reflector shape eliminate cavitation, heat, and pain. So, what we see physically is fiber septa disruption, as well as other nonthermal physical effects.”

She and her colleagues used a specific photography and fixed lighting setup to record the treated areas at baseline, 12 weeks, and 52 weeks, and administered a patient satisfaction questionnaire at 12 and 52 weeks. Prior to treatment, the investigators marked the dimples and ridges intended for treatment. After placing a hydrogel dressing, it took 45-60 minutes to treat both buttocks and thighs with the RAP device. “It was completely noninvasive,” said Dr. Tanzi, who practices in Chevy Chase, Md. “There was no anesthesia used: no incisions and no needles.”

Among 57 patients who were evaluated at 12 weeks, the pain score on a scale of 0-10 was 2.4, while 61.5% strongly agreed and 35.9% agreed that their cellulite appeared improved. In addition, three blinded assessors were able to correctly identify the treated thigh 96% of the time and physician-graded Global Aesthetic Improvement Scale assessments showed 90% improvement of cellulite.

Follow-up analysis

For the current subject satisfaction analysis, the investigators evaluated results from 43 patients in the trial who were followed for at least 52 weeks (a mean of 60 weeks). Of the 43 patients, 30 (69.8%) strongly agreed and 13 (30.2%) agreed that their cellulite “appears improved.” In addition, 29 (67.4%) strongly agreed, 13 (30.2%) agreed, and 1 (2.3%) disagreed with the statement “I feel there is good improvement” of their cellulite.

“Currently, we are evaluating the blinded assessors’ view of these patients and not just going with [findings from] the patient satisfaction survey, but I think these are encouraging results,” Dr. Tanzi said. “We found that 42 out of 43 patients said, ‘yes; I feel that there was good improvement of the area at 52 weeks.’ ”

Dr. Tanzi disclosed that she is a member of the speakers bureau for Eucerin. She is a member of the advisory board for Allergan, Endo Pharmaceuticals, Pulse Biosciences, Sciton, and Soliton. Soliton markets the RAP device.

dbrunk@mdedge.com

Just before Memorial Day, online pharmacy and lab Valisure announced that its testing had found benzene, a known carcinogen, in batches of 78 widely-available sunscreen and after-sun products. The company has petitioned the Food and Drug Administration to recall these products, which include batches from Neutrogena, Banana Boat, CVS Health, and other brands. More than three-quarters of the products are sprays.

©Vesna Andjic/iStockphoto.com

“We’re asking our patients to put sunscreen on from 6 months of age, telling them to do it their entire life, their whole body, multiple times a day,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said in an interview. If benzene-contaminated sunscreen proves to be a widespread problem, he said, “the benzene amounts can add up to a significant chronic exposure over a lifetime.”

In the Valisure statement announcing the findings, Dr. Bunick, who is also quoted in the petition, said that “it is critical that regulatory agencies address benzene contamination in sunscreens, and all topical medications at the manufacturing and final product level, so that all individuals feel safe using sunscreen products.”

The list of products that tested positive is included in the citizen petition, and a full list of products that did not show any contamination is available in an attachment.

Benzene is not an ingredient in sunscreen, and Valisure’s petition suggests that the findings are a result of contamination somewhere in the manufacturing process, not of product degradation.

“This isn’t a sunscreen issue, it’s a manufacturing issue,” said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington. “We don’t want those things to be blurred.”

Assessing the risks

There is a risk of patients taking away the wrong message from these findings.

“People already have ambivalence about sunscreen, and this is just going to make that worse,” Dr. Friedman said in an interview. He pointed out that benzene is present in car exhaust, second-hand smoke, and elsewhere. Inhalation exposure has been the primary focus of toxicology investigations, as has exposure from ingesting things such as contaminated drinking water – not via topical application. “We don’t know how effectively [benzene] gets through the skin, if it gets absorbed systemically, and how that then behaves downstream,” he noted.

On the other hand, ultraviolet radiation is a well-established carcinogen. Avoiding an effective preventive measure such as sunscreen could prove more harmful than exposure to trace amounts of benzene, ultimately to be determined by the FDA.

“Just because those particular products do pose a risk, that doesn’t erase the message that sunscreens are safe and should be used,” Dr. Bunick said. “It’s not mutually exclusive.”

And then there’s the fact that the benzene contamination appears to be fairly limited. “The majority of products we tested, over 200 of them, had no detectable amounts of benzene, and uncontaminated sunscreen should certainly continue to be used,” David Light, CEO of Valisure, told this news organization.

Advising patients

With headlines blaring the news about a carcinogen in sunscreen, patients will be reaching out for advice.

“The number one question patients will have is, ‘What sunscreen do you recommend?’” said Dr. Bunick. “The answer should be to pick a sunscreen that we know wasn’t contaminated. Reassure your patient the ingredients themselves are effective and safe, and that’s not what’s leading to the contamination.”

Dr. Friedman agrees. “We need to be mindful. Dermatologists need to be armed with the facts in order to counsel patients: Sunscreen is still a very important, effective, and safe, scientifically based way to prevent the harmful effects of the sun, in addition to things like sun protective clothing and seeking shade between 10 a.m. and 4 p.m.”

As alarming as Valisure’s findings may seem initially, Dr. Bunick noted a silver lining. “The consumer, the public should feel reassured this report is out there. It shows that someone’s watching out. That’s an important safety message: These things aren’t going undetected.”
 

Just before Memorial Day, online pharmacy and lab Valisure announced that its testing had found benzene, a known carcinogen, in batches of 78 widely-available sunscreen and after-sun products. The company has petitioned the Food and Drug Administration to recall these products, which include batches from Neutrogena, Banana Boat, CVS Health, and other brands. More than three-quarters of the products are sprays.

©Vesna Andjic/iStockphoto.com

“We’re asking our patients to put sunscreen on from 6 months of age, telling them to do it their entire life, their whole body, multiple times a day,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said in an interview. If benzene-contaminated sunscreen proves to be a widespread problem, he said, “the benzene amounts can add up to a significant chronic exposure over a lifetime.”

In the Valisure statement announcing the findings, Dr. Bunick, who is also quoted in the petition, said that “it is critical that regulatory agencies address benzene contamination in sunscreens, and all topical medications at the manufacturing and final product level, so that all individuals feel safe using sunscreen products.”

The list of products that tested positive is included in the citizen petition, and a full list of products that did not show any contamination is available in an attachment.

Benzene is not an ingredient in sunscreen, and Valisure’s petition suggests that the findings are a result of contamination somewhere in the manufacturing process, not of product degradation.

“This isn’t a sunscreen issue, it’s a manufacturing issue,” said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington. “We don’t want those things to be blurred.”

Assessing the risks

There is a risk of patients taking away the wrong message from these findings.

“People already have ambivalence about sunscreen, and this is just going to make that worse,” Dr. Friedman said in an interview. He pointed out that benzene is present in car exhaust, second-hand smoke, and elsewhere. Inhalation exposure has been the primary focus of toxicology investigations, as has exposure from ingesting things such as contaminated drinking water – not via topical application. “We don’t know how effectively [benzene] gets through the skin, if it gets absorbed systemically, and how that then behaves downstream,” he noted.

On the other hand, ultraviolet radiation is a well-established carcinogen. Avoiding an effective preventive measure such as sunscreen could prove more harmful than exposure to trace amounts of benzene, ultimately to be determined by the FDA.

“Just because those particular products do pose a risk, that doesn’t erase the message that sunscreens are safe and should be used,” Dr. Bunick said. “It’s not mutually exclusive.”

And then there’s the fact that the benzene contamination appears to be fairly limited. “The majority of products we tested, over 200 of them, had no detectable amounts of benzene, and uncontaminated sunscreen should certainly continue to be used,” David Light, CEO of Valisure, told this news organization.

Advising patients

With headlines blaring the news about a carcinogen in sunscreen, patients will be reaching out for advice.

“The number one question patients will have is, ‘What sunscreen do you recommend?’” said Dr. Bunick. “The answer should be to pick a sunscreen that we know wasn’t contaminated. Reassure your patient the ingredients themselves are effective and safe, and that’s not what’s leading to the contamination.”

Dr. Friedman agrees. “We need to be mindful. Dermatologists need to be armed with the facts in order to counsel patients: Sunscreen is still a very important, effective, and safe, scientifically based way to prevent the harmful effects of the sun, in addition to things like sun protective clothing and seeking shade between 10 a.m. and 4 p.m.”

As alarming as Valisure’s findings may seem initially, Dr. Bunick noted a silver lining. “The consumer, the public should feel reassured this report is out there. It shows that someone’s watching out. That’s an important safety message: These things aren’t going undetected.”
 

Just before Memorial Day, online pharmacy and lab Valisure announced that its testing had found benzene, a known carcinogen, in batches of 78 widely-available sunscreen and after-sun products. The company has petitioned the Food and Drug Administration to recall these products, which include batches from Neutrogena, Banana Boat, CVS Health, and other brands. More than three-quarters of the products are sprays.

©Vesna Andjic/iStockphoto.com

“We’re asking our patients to put sunscreen on from 6 months of age, telling them to do it their entire life, their whole body, multiple times a day,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said in an interview. If benzene-contaminated sunscreen proves to be a widespread problem, he said, “the benzene amounts can add up to a significant chronic exposure over a lifetime.”

In the Valisure statement announcing the findings, Dr. Bunick, who is also quoted in the petition, said that “it is critical that regulatory agencies address benzene contamination in sunscreens, and all topical medications at the manufacturing and final product level, so that all individuals feel safe using sunscreen products.”

The list of products that tested positive is included in the citizen petition, and a full list of products that did not show any contamination is available in an attachment.

Benzene is not an ingredient in sunscreen, and Valisure’s petition suggests that the findings are a result of contamination somewhere in the manufacturing process, not of product degradation.

“This isn’t a sunscreen issue, it’s a manufacturing issue,” said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington. “We don’t want those things to be blurred.”

Assessing the risks

There is a risk of patients taking away the wrong message from these findings.

“People already have ambivalence about sunscreen, and this is just going to make that worse,” Dr. Friedman said in an interview. He pointed out that benzene is present in car exhaust, second-hand smoke, and elsewhere. Inhalation exposure has been the primary focus of toxicology investigations, as has exposure from ingesting things such as contaminated drinking water – not via topical application. “We don’t know how effectively [benzene] gets through the skin, if it gets absorbed systemically, and how that then behaves downstream,” he noted.

On the other hand, ultraviolet radiation is a well-established carcinogen. Avoiding an effective preventive measure such as sunscreen could prove more harmful than exposure to trace amounts of benzene, ultimately to be determined by the FDA.

“Just because those particular products do pose a risk, that doesn’t erase the message that sunscreens are safe and should be used,” Dr. Bunick said. “It’s not mutually exclusive.”

And then there’s the fact that the benzene contamination appears to be fairly limited. “The majority of products we tested, over 200 of them, had no detectable amounts of benzene, and uncontaminated sunscreen should certainly continue to be used,” David Light, CEO of Valisure, told this news organization.

Advising patients

With headlines blaring the news about a carcinogen in sunscreen, patients will be reaching out for advice.

“The number one question patients will have is, ‘What sunscreen do you recommend?’” said Dr. Bunick. “The answer should be to pick a sunscreen that we know wasn’t contaminated. Reassure your patient the ingredients themselves are effective and safe, and that’s not what’s leading to the contamination.”

Dr. Friedman agrees. “We need to be mindful. Dermatologists need to be armed with the facts in order to counsel patients: Sunscreen is still a very important, effective, and safe, scientifically based way to prevent the harmful effects of the sun, in addition to things like sun protective clothing and seeking shade between 10 a.m. and 4 p.m.”

As alarming as Valisure’s findings may seem initially, Dr. Bunick noted a silver lining. “The consumer, the public should feel reassured this report is out there. It shows that someone’s watching out. That’s an important safety message: These things aren’t going undetected.”
 

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

With the COVID-19 pandemic, already high rates of suicide, depression, and burnout among physicians became even more acute. Yet, 3 years after the Federation of State Medical Boards issued recommendations on what questions about mental health status license applications should – or mostly should not – include, only North Carolina fully complies with all four recommendations, and most states comply with two or fewer, a study of state medical board applications has found (JAMA. 2021 May 18;325[19];2017-8).

Questions about mental health history or “its hypothetical effect on competency,” violate the Americans with Disabilities Act, the study authors stated. In a research letter to JAMA, the authors also reported that five state boards do not comply with any of the FSMB recommendations. Twenty-four states comply with three of the four recommendations.

Overall, the mean consistency score was 2.1, which means state medical licensing applications typically run afoul of the Americans With Disabilities Act when it comes to mental health history of applicants.

“No one should ever wonder, ‘Will I lose my job, or should I get help?’ ” said co–senior author Jessica A. Gold, MD, MS, a psychiatrist at Washington University in St. Louis. “This should absolutely never be a question on someone’s mind. And the fact that it is, in medicine, is a problem that needs to be solved. I hope that people are beginning to see that, and we can make a change to get people the help they need before it is too late.”
 

High rates of depression, suicide

She noted that before COVID-19, physicians already had higher rates of depression, burnout, and suicide than the general population. “Over COVID-19, it has become clear that the mental health of physicians has become additionally compounded,” Dr. Gold said.

One study found that physicians had a 44% higher rate of suicide (PLoS One. 2019 Dec;14[12]:e0226361), but they’re notoriously reluctant to seek out mental health care. A 2017 study reported that 40% of physicians would be reluctant to seek mental health care because of concerns about their licensure (Mayo Clin Proc. 2017;92[10]:1486-93).

As the pandemic went on, Dr. Gold and her colleagues decided to study whether state boards had improved their compliance with the FSMB recommendations issued in 2018. Those recommendations include these four limitations regarding questions about mental health conditions on license applications:

• Include only when they result in impairment.
• Include only when the mental health conditions are current – that is, when they’ve occurred within the past 2 years.
• Provide safe haven nonreporting – that is, allow physicians to not report previously diagnosed and treated mental health conditions if they’re being monitored and are in good standing with a physician health program.
• Include supportive or nonjudgmental language about seeking mental health care.

The study considered board applications that had questions about mental health status as consistent with the first three recommendations. Seventeen states complied.

Thirty-nine state boards complied with the first recommendation regarding impairment; 41 with the second recommendation about near-term history; 25 with safe-haven nonreporting. Only eight states were consistent with the recommendation on supportive language.

The ADA limits inquiries about an applicant’s impairment to only current conditions. In a 2017 study, only 21 state boards had limited questions to current impairment. “This is a significant improvement, but this still means the rest of the states are violating an actual law,” Dr. Gold said. “Another plus is that 17 states asked no questions at all that could require mental health disclosure. This, too is significant because it highlights change in thinking.”

But still, the fact that five states didn’t comply with any recommendation and only one followed all of them is “utterly unacceptable,” Dr. Gold said. “Instead, we should have universal adoption of FSMB recommendations.”
 

Time to remove stigma

Michael F. Myers, MD, a clinical psychiatrist at the State University of New York, Brooklyn, said removing the stigma of seeking help for mental health conditions is especially important for physicians. He’s written several books about physician mental health, including his latest, “Becoming a Doctor’s Doctor: A Memoir.”

“I would say at least 15% of the families that I interviewed who lost a physician loved one to suicide have said the doctor was petrified of going for professional help because of fears of what this could do to their medical license,” he said. “It is extremely important that those licensing questions will be either brought up to speed, or ­– the ones that are clearly violating the ADA – that they be removed.”

Applications for hospital privileges can also run afoul of the same ADA standard, Dr. Myers added. “Physicians have told me that when they go to get medical privileges at a medical center, they get asked all kinds of questions that are outdated, that are intrusive, that violate the ADA,” he said.

Credentialing is another area that Dr. Gold and her colleagues are interested in studying, she said. “Sometimes the licensing applications can be fine, but then the hospital someone is applying to work at can ask the same illegal questions anyway,” she said. “So it doesn’t matter that the state fixed the problem because the hospital asked them anyway. You feel your job is at risk in the same way, so you still don’t get help.”

Dr. Gold and Dr. Myers have no relevant financial relationships to disclose.

With the COVID-19 pandemic, already high rates of suicide, depression, and burnout among physicians became even more acute. Yet, 3 years after the Federation of State Medical Boards issued recommendations on what questions about mental health status license applications should – or mostly should not – include, only North Carolina fully complies with all four recommendations, and most states comply with two or fewer, a study of state medical board applications has found (JAMA. 2021 May 18;325[19];2017-8).

Questions about mental health history or “its hypothetical effect on competency,” violate the Americans with Disabilities Act, the study authors stated. In a research letter to JAMA, the authors also reported that five state boards do not comply with any of the FSMB recommendations. Twenty-four states comply with three of the four recommendations.

Overall, the mean consistency score was 2.1, which means state medical licensing applications typically run afoul of the Americans With Disabilities Act when it comes to mental health history of applicants.

“No one should ever wonder, ‘Will I lose my job, or should I get help?’ ” said co–senior author Jessica A. Gold, MD, MS, a psychiatrist at Washington University in St. Louis. “This should absolutely never be a question on someone’s mind. And the fact that it is, in medicine, is a problem that needs to be solved. I hope that people are beginning to see that, and we can make a change to get people the help they need before it is too late.”
 

High rates of depression, suicide

She noted that before COVID-19, physicians already had higher rates of depression, burnout, and suicide than the general population. “Over COVID-19, it has become clear that the mental health of physicians has become additionally compounded,” Dr. Gold said.

One study found that physicians had a 44% higher rate of suicide (PLoS One. 2019 Dec;14[12]:e0226361), but they’re notoriously reluctant to seek out mental health care. A 2017 study reported that 40% of physicians would be reluctant to seek mental health care because of concerns about their licensure (Mayo Clin Proc. 2017;92[10]:1486-93).

As the pandemic went on, Dr. Gold and her colleagues decided to study whether state boards had improved their compliance with the FSMB recommendations issued in 2018. Those recommendations include these four limitations regarding questions about mental health conditions on license applications:

• Include only when they result in impairment.
• Include only when the mental health conditions are current – that is, when they’ve occurred within the past 2 years.
• Provide safe haven nonreporting – that is, allow physicians to not report previously diagnosed and treated mental health conditions if they’re being monitored and are in good standing with a physician health program.
• Include supportive or nonjudgmental language about seeking mental health care.

The study considered board applications that had questions about mental health status as consistent with the first three recommendations. Seventeen states complied.

Thirty-nine state boards complied with the first recommendation regarding impairment; 41 with the second recommendation about near-term history; 25 with safe-haven nonreporting. Only eight states were consistent with the recommendation on supportive language.

The ADA limits inquiries about an applicant’s impairment to only current conditions. In a 2017 study, only 21 state boards had limited questions to current impairment. “This is a significant improvement, but this still means the rest of the states are violating an actual law,” Dr. Gold said. “Another plus is that 17 states asked no questions at all that could require mental health disclosure. This, too is significant because it highlights change in thinking.”

But still, the fact that five states didn’t comply with any recommendation and only one followed all of them is “utterly unacceptable,” Dr. Gold said. “Instead, we should have universal adoption of FSMB recommendations.”
 

Time to remove stigma

Michael F. Myers, MD, a clinical psychiatrist at the State University of New York, Brooklyn, said removing the stigma of seeking help for mental health conditions is especially important for physicians. He’s written several books about physician mental health, including his latest, “Becoming a Doctor’s Doctor: A Memoir.”

“I would say at least 15% of the families that I interviewed who lost a physician loved one to suicide have said the doctor was petrified of going for professional help because of fears of what this could do to their medical license,” he said. “It is extremely important that those licensing questions will be either brought up to speed, or ­– the ones that are clearly violating the ADA – that they be removed.”

Applications for hospital privileges can also run afoul of the same ADA standard, Dr. Myers added. “Physicians have told me that when they go to get medical privileges at a medical center, they get asked all kinds of questions that are outdated, that are intrusive, that violate the ADA,” he said.

Credentialing is another area that Dr. Gold and her colleagues are interested in studying, she said. “Sometimes the licensing applications can be fine, but then the hospital someone is applying to work at can ask the same illegal questions anyway,” she said. “So it doesn’t matter that the state fixed the problem because the hospital asked them anyway. You feel your job is at risk in the same way, so you still don’t get help.”

Dr. Gold and Dr. Myers have no relevant financial relationships to disclose.

With the COVID-19 pandemic, already high rates of suicide, depression, and burnout among physicians became even more acute. Yet, 3 years after the Federation of State Medical Boards issued recommendations on what questions about mental health status license applications should – or mostly should not – include, only North Carolina fully complies with all four recommendations, and most states comply with two or fewer, a study of state medical board applications has found (JAMA. 2021 May 18;325[19];2017-8).

Questions about mental health history or “its hypothetical effect on competency,” violate the Americans with Disabilities Act, the study authors stated. In a research letter to JAMA, the authors also reported that five state boards do not comply with any of the FSMB recommendations. Twenty-four states comply with three of the four recommendations.

Overall, the mean consistency score was 2.1, which means state medical licensing applications typically run afoul of the Americans With Disabilities Act when it comes to mental health history of applicants.

“No one should ever wonder, ‘Will I lose my job, or should I get help?’ ” said co–senior author Jessica A. Gold, MD, MS, a psychiatrist at Washington University in St. Louis. “This should absolutely never be a question on someone’s mind. And the fact that it is, in medicine, is a problem that needs to be solved. I hope that people are beginning to see that, and we can make a change to get people the help they need before it is too late.”
 

High rates of depression, suicide

She noted that before COVID-19, physicians already had higher rates of depression, burnout, and suicide than the general population. “Over COVID-19, it has become clear that the mental health of physicians has become additionally compounded,” Dr. Gold said.

One study found that physicians had a 44% higher rate of suicide (PLoS One. 2019 Dec;14[12]:e0226361), but they’re notoriously reluctant to seek out mental health care. A 2017 study reported that 40% of physicians would be reluctant to seek mental health care because of concerns about their licensure (Mayo Clin Proc. 2017;92[10]:1486-93).

As the pandemic went on, Dr. Gold and her colleagues decided to study whether state boards had improved their compliance with the FSMB recommendations issued in 2018. Those recommendations include these four limitations regarding questions about mental health conditions on license applications:

• Include only when they result in impairment.
• Include only when the mental health conditions are current – that is, when they’ve occurred within the past 2 years.
• Provide safe haven nonreporting – that is, allow physicians to not report previously diagnosed and treated mental health conditions if they’re being monitored and are in good standing with a physician health program.
• Include supportive or nonjudgmental language about seeking mental health care.

The study considered board applications that had questions about mental health status as consistent with the first three recommendations. Seventeen states complied.

Thirty-nine state boards complied with the first recommendation regarding impairment; 41 with the second recommendation about near-term history; 25 with safe-haven nonreporting. Only eight states were consistent with the recommendation on supportive language.

The ADA limits inquiries about an applicant’s impairment to only current conditions. In a 2017 study, only 21 state boards had limited questions to current impairment. “This is a significant improvement, but this still means the rest of the states are violating an actual law,” Dr. Gold said. “Another plus is that 17 states asked no questions at all that could require mental health disclosure. This, too is significant because it highlights change in thinking.”

But still, the fact that five states didn’t comply with any recommendation and only one followed all of them is “utterly unacceptable,” Dr. Gold said. “Instead, we should have universal adoption of FSMB recommendations.”
 

Time to remove stigma

Michael F. Myers, MD, a clinical psychiatrist at the State University of New York, Brooklyn, said removing the stigma of seeking help for mental health conditions is especially important for physicians. He’s written several books about physician mental health, including his latest, “Becoming a Doctor’s Doctor: A Memoir.”

“I would say at least 15% of the families that I interviewed who lost a physician loved one to suicide have said the doctor was petrified of going for professional help because of fears of what this could do to their medical license,” he said. “It is extremely important that those licensing questions will be either brought up to speed, or ­– the ones that are clearly violating the ADA – that they be removed.”

Applications for hospital privileges can also run afoul of the same ADA standard, Dr. Myers added. “Physicians have told me that when they go to get medical privileges at a medical center, they get asked all kinds of questions that are outdated, that are intrusive, that violate the ADA,” he said.

Credentialing is another area that Dr. Gold and her colleagues are interested in studying, she said. “Sometimes the licensing applications can be fine, but then the hospital someone is applying to work at can ask the same illegal questions anyway,” she said. “So it doesn’t matter that the state fixed the problem because the hospital asked them anyway. You feel your job is at risk in the same way, so you still don’t get help.”

Dr. Gold and Dr. Myers have no relevant financial relationships to disclose.

Using belimumab after rituximab to treat patients with systemic lupus erythematosus (SLE) refractory to conventional therapy not only significantly decreased levels of serum IgG anti-dsDNA antibody levels but also prolonged the time before severe flares of disease occurred in the phase 2b BEAT-LUPUS (Belimumab after B cell depletion in SLE) study.

The trial’s primary outcome of serum IgG anti-dsDNA antibody levels showed a decline from a geometric mean of 162 IU/mL at baseline to 69 IU/mL at 24 weeks and 47 IU/mL at 1 year in patients treated with belimumab (Benlysta) after rituximab (Rituxan and biosimilars). These reductions were significantly lower than the values seen in the placebo after rituximab arm (a respective 121 IU/mL, 99 IU/mL, and 103 IU/mL; P < .001).

Just 3 patients who received belimumab versus 10 who received placebo after rituximab experienced a severe BILAG (British Isles Lupus Assessment Group) index A flare by the end of the study at 52 weeks. The hazard ratio (HR) for the flare reduction was 0.27 (P = .03), indicating a 73% reduction.

The use of belimumab rather than a placebo also led to a small reduction in total serum IgG, and significantly suppressed B-cell repopulation (P = .03).

These results need confirming in a larger, phase 3 trial, the trial’s principal investigator, Michael Ehrenstein, PhD, said at the annual European Congress of Rheumatology. They are “clearly encouraging” and “support the hypothesis that BAFF [B-cell–activating factor] can drive flares after rituximab,” he said.

Although B-cell depletion with rituximab is recommended by national and international guidelines to treat some patients with SLE who are refractory to conventional therapy, its use is not licensed.

“Certainly, rituximab is a controversial drug in lupus,” Dr. Ehrenstein, a consultant rheumatologist based at University College London, said in an interview. Although there is real-world evidence from registries and open-label studies suggesting that it is widely used and effective in some patients, the randomized, controlled trials conducted with rituximab about 10 years ago failed to meet their primary endpoints.

“A lot has been written about why that was, but probably the biggest reason was the high dose of steroids in both groups,” Dr. Ehrenstein said. To try to avoid muddying the waters of the BEAT-LUPUS trial findings, the maximum dose of prednisolone allowed to be used as background therapy was 20 mg/day. The trial’s investigators were also encouraged to reduce the baseline steroid dose to at least 50% by the trial’s 6-month halfway point.

“We tried to reflect what was going on in the U.K.,” Dr. Ehrenstein said, noting that the inspiration for the trial was a patient who had received sequential rituximab treatment. Although she got better with each cycle of rituximab, when her disease flared it would be worse than the time before, with increasingly higher anti-dsDNA levels recorded. The reason for this seemed to be because of increasing BAFF levels, and so the hypothesis was that if rituximab was associated with increased BAFF levels, then co-targeting BAFF with belimumab should be able to prevent those flares from happening.

The BEAT-LUPUS trial has been a huge collaborative effort and was conducted across 16 U.K. centers. From initial funding to the data analysis, it has taken 6 years to complete and was made possible by a unique partnership between Versus Arthritis, University College London Hospitals Biomedical Research Center, the National Institute for Health Research UK Musculoskeletal Translational Research Collaboration, and GlaxoSmithKline (GSK). GSK provided belimumab free of charge, as well as additional funding, but had no role in the design of the study and will not have any role going forward.

From an initial 172 patients assessed for eligibility, 52 patients were finally enrolled into the trial and received rituximab as two infusions given 2 weeks apart. Patients were then randomized in a double-blind manner to receive either belimumab (n = 26) or placebo (n = 26) 4-8 weeks after their first dose of rituximab. The intention-to-treat population consisted of 43 patients.

The use of belimumab after rituximab did not increase the risk for infection – serious or otherwise – or adverse effects, Dr. Ehrenstein reported. Serious adverse events were reported in six (23%) patients in each arm, and serious infections were seen in two (8%) of the belimumab- and four (15%) of the placebo-treated patients.

“I think the take-home message is that it seems that belimumab can reduce the number of severe flares that occur after rituximab therapy,” Dr. Ehrenstein said. “It’s promising, but not definitive,” he added. The next step is of course to publish these data and to perform a phase 3 trial.

In the discussion time following the presentation, session moderator Xavier Mariette, MD, PhD, of Bicêtre Hospital, Paris-Saclay University, asked why not give belimumab first before rituximab if using belimumab afterward works?

“Our strategy was driven by the observation that BAFF levels surged after rituximab, and therefore it’s logical to give the belimumab to block that BAFF surge,” he answered.

“Certainly, there are ideas that belimumab releases mature B cells into the circulation and rituximab can target that,” he added. That strategy is under investigation in the BLISS-BELIEVE trial, which should also report by the end of this year. It’s a much larger, phase 3 trial, involving nearly 300 patients and is sponsored by GSK.

“Clearly, this is a combination treatment [but] whether you give one before the other is uncertain,” Dr. Ehrenstein observed.

Another member of the viewing audience asked whether it would have been a fairer comparison if another dose of rituximab had been given to patients at week 24 instead of no treatment. Dr. Ehrenstein noted that it was a “good point” to make, but the investigators mainly wanted to answer whether giving belimumab after rituximab would target BAFF and thereby drop serum anti-dsDNA antibody levels. He said that a full trial of rituximab for patients with SLE, perhaps adding this extra dose, needs to be conducted.

Dr. Ehrenstein disclosed receiving research funding and educational grants from GSK and participating in advisory panels for the company.

Using belimumab after rituximab to treat patients with systemic lupus erythematosus (SLE) refractory to conventional therapy not only significantly decreased levels of serum IgG anti-dsDNA antibody levels but also prolonged the time before severe flares of disease occurred in the phase 2b BEAT-LUPUS (Belimumab after B cell depletion in SLE) study.

The trial’s primary outcome of serum IgG anti-dsDNA antibody levels showed a decline from a geometric mean of 162 IU/mL at baseline to 69 IU/mL at 24 weeks and 47 IU/mL at 1 year in patients treated with belimumab (Benlysta) after rituximab (Rituxan and biosimilars). These reductions were significantly lower than the values seen in the placebo after rituximab arm (a respective 121 IU/mL, 99 IU/mL, and 103 IU/mL; P < .001).

Just 3 patients who received belimumab versus 10 who received placebo after rituximab experienced a severe BILAG (British Isles Lupus Assessment Group) index A flare by the end of the study at 52 weeks. The hazard ratio (HR) for the flare reduction was 0.27 (P = .03), indicating a 73% reduction.

The use of belimumab rather than a placebo also led to a small reduction in total serum IgG, and significantly suppressed B-cell repopulation (P = .03).

These results need confirming in a larger, phase 3 trial, the trial’s principal investigator, Michael Ehrenstein, PhD, said at the annual European Congress of Rheumatology. They are “clearly encouraging” and “support the hypothesis that BAFF [B-cell–activating factor] can drive flares after rituximab,” he said.

Although B-cell depletion with rituximab is recommended by national and international guidelines to treat some patients with SLE who are refractory to conventional therapy, its use is not licensed.

“Certainly, rituximab is a controversial drug in lupus,” Dr. Ehrenstein, a consultant rheumatologist based at University College London, said in an interview. Although there is real-world evidence from registries and open-label studies suggesting that it is widely used and effective in some patients, the randomized, controlled trials conducted with rituximab about 10 years ago failed to meet their primary endpoints.

“A lot has been written about why that was, but probably the biggest reason was the high dose of steroids in both groups,” Dr. Ehrenstein said. To try to avoid muddying the waters of the BEAT-LUPUS trial findings, the maximum dose of prednisolone allowed to be used as background therapy was 20 mg/day. The trial’s investigators were also encouraged to reduce the baseline steroid dose to at least 50% by the trial’s 6-month halfway point.

“We tried to reflect what was going on in the U.K.,” Dr. Ehrenstein said, noting that the inspiration for the trial was a patient who had received sequential rituximab treatment. Although she got better with each cycle of rituximab, when her disease flared it would be worse than the time before, with increasingly higher anti-dsDNA levels recorded. The reason for this seemed to be because of increasing BAFF levels, and so the hypothesis was that if rituximab was associated with increased BAFF levels, then co-targeting BAFF with belimumab should be able to prevent those flares from happening.

The BEAT-LUPUS trial has been a huge collaborative effort and was conducted across 16 U.K. centers. From initial funding to the data analysis, it has taken 6 years to complete and was made possible by a unique partnership between Versus Arthritis, University College London Hospitals Biomedical Research Center, the National Institute for Health Research UK Musculoskeletal Translational Research Collaboration, and GlaxoSmithKline (GSK). GSK provided belimumab free of charge, as well as additional funding, but had no role in the design of the study and will not have any role going forward.

From an initial 172 patients assessed for eligibility, 52 patients were finally enrolled into the trial and received rituximab as two infusions given 2 weeks apart. Patients were then randomized in a double-blind manner to receive either belimumab (n = 26) or placebo (n = 26) 4-8 weeks after their first dose of rituximab. The intention-to-treat population consisted of 43 patients.

The use of belimumab after rituximab did not increase the risk for infection – serious or otherwise – or adverse effects, Dr. Ehrenstein reported. Serious adverse events were reported in six (23%) patients in each arm, and serious infections were seen in two (8%) of the belimumab- and four (15%) of the placebo-treated patients.

“I think the take-home message is that it seems that belimumab can reduce the number of severe flares that occur after rituximab therapy,” Dr. Ehrenstein said. “It’s promising, but not definitive,” he added. The next step is of course to publish these data and to perform a phase 3 trial.

In the discussion time following the presentation, session moderator Xavier Mariette, MD, PhD, of Bicêtre Hospital, Paris-Saclay University, asked why not give belimumab first before rituximab if using belimumab afterward works?

“Our strategy was driven by the observation that BAFF levels surged after rituximab, and therefore it’s logical to give the belimumab to block that BAFF surge,” he answered.

“Certainly, there are ideas that belimumab releases mature B cells into the circulation and rituximab can target that,” he added. That strategy is under investigation in the BLISS-BELIEVE trial, which should also report by the end of this year. It’s a much larger, phase 3 trial, involving nearly 300 patients and is sponsored by GSK.

“Clearly, this is a combination treatment [but] whether you give one before the other is uncertain,” Dr. Ehrenstein observed.

Another member of the viewing audience asked whether it would have been a fairer comparison if another dose of rituximab had been given to patients at week 24 instead of no treatment. Dr. Ehrenstein noted that it was a “good point” to make, but the investigators mainly wanted to answer whether giving belimumab after rituximab would target BAFF and thereby drop serum anti-dsDNA antibody levels. He said that a full trial of rituximab for patients with SLE, perhaps adding this extra dose, needs to be conducted.

Dr. Ehrenstein disclosed receiving research funding and educational grants from GSK and participating in advisory panels for the company.

Using belimumab after rituximab to treat patients with systemic lupus erythematosus (SLE) refractory to conventional therapy not only significantly decreased levels of serum IgG anti-dsDNA antibody levels but also prolonged the time before severe flares of disease occurred in the phase 2b BEAT-LUPUS (Belimumab after B cell depletion in SLE) study.

The trial’s primary outcome of serum IgG anti-dsDNA antibody levels showed a decline from a geometric mean of 162 IU/mL at baseline to 69 IU/mL at 24 weeks and 47 IU/mL at 1 year in patients treated with belimumab (Benlysta) after rituximab (Rituxan and biosimilars). These reductions were significantly lower than the values seen in the placebo after rituximab arm (a respective 121 IU/mL, 99 IU/mL, and 103 IU/mL; P < .001).

Just 3 patients who received belimumab versus 10 who received placebo after rituximab experienced a severe BILAG (British Isles Lupus Assessment Group) index A flare by the end of the study at 52 weeks. The hazard ratio (HR) for the flare reduction was 0.27 (P = .03), indicating a 73% reduction.

The use of belimumab rather than a placebo also led to a small reduction in total serum IgG, and significantly suppressed B-cell repopulation (P = .03).

These results need confirming in a larger, phase 3 trial, the trial’s principal investigator, Michael Ehrenstein, PhD, said at the annual European Congress of Rheumatology. They are “clearly encouraging” and “support the hypothesis that BAFF [B-cell–activating factor] can drive flares after rituximab,” he said.

Although B-cell depletion with rituximab is recommended by national and international guidelines to treat some patients with SLE who are refractory to conventional therapy, its use is not licensed.

“Certainly, rituximab is a controversial drug in lupus,” Dr. Ehrenstein, a consultant rheumatologist based at University College London, said in an interview. Although there is real-world evidence from registries and open-label studies suggesting that it is widely used and effective in some patients, the randomized, controlled trials conducted with rituximab about 10 years ago failed to meet their primary endpoints.

“A lot has been written about why that was, but probably the biggest reason was the high dose of steroids in both groups,” Dr. Ehrenstein said. To try to avoid muddying the waters of the BEAT-LUPUS trial findings, the maximum dose of prednisolone allowed to be used as background therapy was 20 mg/day. The trial’s investigators were also encouraged to reduce the baseline steroid dose to at least 50% by the trial’s 6-month halfway point.

“We tried to reflect what was going on in the U.K.,” Dr. Ehrenstein said, noting that the inspiration for the trial was a patient who had received sequential rituximab treatment. Although she got better with each cycle of rituximab, when her disease flared it would be worse than the time before, with increasingly higher anti-dsDNA levels recorded. The reason for this seemed to be because of increasing BAFF levels, and so the hypothesis was that if rituximab was associated with increased BAFF levels, then co-targeting BAFF with belimumab should be able to prevent those flares from happening.

The BEAT-LUPUS trial has been a huge collaborative effort and was conducted across 16 U.K. centers. From initial funding to the data analysis, it has taken 6 years to complete and was made possible by a unique partnership between Versus Arthritis, University College London Hospitals Biomedical Research Center, the National Institute for Health Research UK Musculoskeletal Translational Research Collaboration, and GlaxoSmithKline (GSK). GSK provided belimumab free of charge, as well as additional funding, but had no role in the design of the study and will not have any role going forward.

From an initial 172 patients assessed for eligibility, 52 patients were finally enrolled into the trial and received rituximab as two infusions given 2 weeks apart. Patients were then randomized in a double-blind manner to receive either belimumab (n = 26) or placebo (n = 26) 4-8 weeks after their first dose of rituximab. The intention-to-treat population consisted of 43 patients.

The use of belimumab after rituximab did not increase the risk for infection – serious or otherwise – or adverse effects, Dr. Ehrenstein reported. Serious adverse events were reported in six (23%) patients in each arm, and serious infections were seen in two (8%) of the belimumab- and four (15%) of the placebo-treated patients.

“I think the take-home message is that it seems that belimumab can reduce the number of severe flares that occur after rituximab therapy,” Dr. Ehrenstein said. “It’s promising, but not definitive,” he added. The next step is of course to publish these data and to perform a phase 3 trial.

In the discussion time following the presentation, session moderator Xavier Mariette, MD, PhD, of Bicêtre Hospital, Paris-Saclay University, asked why not give belimumab first before rituximab if using belimumab afterward works?

“Our strategy was driven by the observation that BAFF levels surged after rituximab, and therefore it’s logical to give the belimumab to block that BAFF surge,” he answered.

“Certainly, there are ideas that belimumab releases mature B cells into the circulation and rituximab can target that,” he added. That strategy is under investigation in the BLISS-BELIEVE trial, which should also report by the end of this year. It’s a much larger, phase 3 trial, involving nearly 300 patients and is sponsored by GSK.

“Clearly, this is a combination treatment [but] whether you give one before the other is uncertain,” Dr. Ehrenstein observed.

Another member of the viewing audience asked whether it would have been a fairer comparison if another dose of rituximab had been given to patients at week 24 instead of no treatment. Dr. Ehrenstein noted that it was a “good point” to make, but the investigators mainly wanted to answer whether giving belimumab after rituximab would target BAFF and thereby drop serum anti-dsDNA antibody levels. He said that a full trial of rituximab for patients with SLE, perhaps adding this extra dose, needs to be conducted.

Dr. Ehrenstein disclosed receiving research funding and educational grants from GSK and participating in advisory panels for the company.

Almost 14% of transected invasive melanoma biopsies at the University of Alabama at Birmingham were up-staged on final surgical pathology, in a review of cases at the university.

Had their true Breslow depths been known before definitive surgery, sentinel lymph node (SLN) biopsies and wider surgical margins would likely have been recommended.

The findings led the investigators to conclude that a second biopsy should be considered when the first one is transected to ensure surgical and other management decisions are based on an accurate Breslow depth.

A second biopsy is especially warranted for broadly transected biopsies and transected T1a tumors with gross residual tumor or pigment on preoperative exam; both scenarios significantly increased the risk of up-staging in the study, according to lead investigator James Duncan, MD, a Mohs surgery and dermatologic oncology fellow at the University of Alabama at Birmingham, who presented the findings at the annual meeting of the American College of Mohs Surgery.

“Accurate staging of malignancies, especially melanoma, is critical to determine prognosis and the best treatment approach,” said Vishal Patel, MD, director of cutaneous oncology at George Washington University, Washington, when asked for comment.

“This study identifies how transected biopsies can underestimate a melanoma’s true depth and thus impact treatment and outcomes. The authors highlight that when a biopsy is transected, or there is notable pigment at the base, attempts should be taken to sample the remaining tumor prior to surgery so the accurate tumor depth can be determined and treatment options be fully discussed with the patient,” Dr. Patel said.

The Birmingham team reviewed invasive melanoma cases at their university from 2017 to 2019.

Almost half (49.6%) of the 726 melanomas they identified were transected on biopsy, which is in line with prior reports. About 60% of the patients were men and 98% were White; the average age was 63 years.

Of the 360 transected tumors, 49 (13.6%) had up-staging at final excision that “would have prompted discussion of alternate surgical treatment such as SLN biopsy or wider surgical margins,” the team said.

Of the 89 transected pT1a melanomas identified, 47.1% with gross residual tumor or pigment on preoperative physical examination were up-staged following excision versus 6.9% with no remaining pigment or tumor prior to surgery (P < .01).

Broadly transected tumors were up-staged in 21.7% of cases versus 4.9% of focally transected tumors (P = .038). The average increase in Breslow depth for broadly transected tumors was 1.03 mm versus 0.03 mm for focally transected lesions (P = .04).

Shave biopsies, ulceration, and lack of concern for melanoma at the initial biopsy were among the factors associated with a higher risk of transection.

Superficial spreading melanoma was the most common subtype. Tumors were evenly distributed between the head, neck, and extremities. The average Breslow depth was 1.51 mm, and the majority of tumors were pT1a or pT2a.

The review excluded melanoma in situ, recurrences, metastases, noncutaneous melanomas, and biopsies where deep margin status was unknown.

There was no funding for the study, and Dr. Duncan and Dr. Patel had no relevant disclosures.

aotto@mdedge.com

Almost 14% of transected invasive melanoma biopsies at the University of Alabama at Birmingham were up-staged on final surgical pathology, in a review of cases at the university.

Had their true Breslow depths been known before definitive surgery, sentinel lymph node (SLN) biopsies and wider surgical margins would likely have been recommended.

The findings led the investigators to conclude that a second biopsy should be considered when the first one is transected to ensure surgical and other management decisions are based on an accurate Breslow depth.

A second biopsy is especially warranted for broadly transected biopsies and transected T1a tumors with gross residual tumor or pigment on preoperative exam; both scenarios significantly increased the risk of up-staging in the study, according to lead investigator James Duncan, MD, a Mohs surgery and dermatologic oncology fellow at the University of Alabama at Birmingham, who presented the findings at the annual meeting of the American College of Mohs Surgery.

“Accurate staging of malignancies, especially melanoma, is critical to determine prognosis and the best treatment approach,” said Vishal Patel, MD, director of cutaneous oncology at George Washington University, Washington, when asked for comment.

“This study identifies how transected biopsies can underestimate a melanoma’s true depth and thus impact treatment and outcomes. The authors highlight that when a biopsy is transected, or there is notable pigment at the base, attempts should be taken to sample the remaining tumor prior to surgery so the accurate tumor depth can be determined and treatment options be fully discussed with the patient,” Dr. Patel said.

The Birmingham team reviewed invasive melanoma cases at their university from 2017 to 2019.

Almost half (49.6%) of the 726 melanomas they identified were transected on biopsy, which is in line with prior reports. About 60% of the patients were men and 98% were White; the average age was 63 years.

Of the 360 transected tumors, 49 (13.6%) had up-staging at final excision that “would have prompted discussion of alternate surgical treatment such as SLN biopsy or wider surgical margins,” the team said.

Of the 89 transected pT1a melanomas identified, 47.1% with gross residual tumor or pigment on preoperative physical examination were up-staged following excision versus 6.9% with no remaining pigment or tumor prior to surgery (P < .01).

Broadly transected tumors were up-staged in 21.7% of cases versus 4.9% of focally transected tumors (P = .038). The average increase in Breslow depth for broadly transected tumors was 1.03 mm versus 0.03 mm for focally transected lesions (P = .04).

Shave biopsies, ulceration, and lack of concern for melanoma at the initial biopsy were among the factors associated with a higher risk of transection.

Superficial spreading melanoma was the most common subtype. Tumors were evenly distributed between the head, neck, and extremities. The average Breslow depth was 1.51 mm, and the majority of tumors were pT1a or pT2a.

The review excluded melanoma in situ, recurrences, metastases, noncutaneous melanomas, and biopsies where deep margin status was unknown.

There was no funding for the study, and Dr. Duncan and Dr. Patel had no relevant disclosures.

aotto@mdedge.com

Almost 14% of transected invasive melanoma biopsies at the University of Alabama at Birmingham were up-staged on final surgical pathology, in a review of cases at the university.

Had their true Breslow depths been known before definitive surgery, sentinel lymph node (SLN) biopsies and wider surgical margins would likely have been recommended.

The findings led the investigators to conclude that a second biopsy should be considered when the first one is transected to ensure surgical and other management decisions are based on an accurate Breslow depth.

A second biopsy is especially warranted for broadly transected biopsies and transected T1a tumors with gross residual tumor or pigment on preoperative exam; both scenarios significantly increased the risk of up-staging in the study, according to lead investigator James Duncan, MD, a Mohs surgery and dermatologic oncology fellow at the University of Alabama at Birmingham, who presented the findings at the annual meeting of the American College of Mohs Surgery.

“Accurate staging of malignancies, especially melanoma, is critical to determine prognosis and the best treatment approach,” said Vishal Patel, MD, director of cutaneous oncology at George Washington University, Washington, when asked for comment.

“This study identifies how transected biopsies can underestimate a melanoma’s true depth and thus impact treatment and outcomes. The authors highlight that when a biopsy is transected, or there is notable pigment at the base, attempts should be taken to sample the remaining tumor prior to surgery so the accurate tumor depth can be determined and treatment options be fully discussed with the patient,” Dr. Patel said.

The Birmingham team reviewed invasive melanoma cases at their university from 2017 to 2019.

Almost half (49.6%) of the 726 melanomas they identified were transected on biopsy, which is in line with prior reports. About 60% of the patients were men and 98% were White; the average age was 63 years.

Of the 360 transected tumors, 49 (13.6%) had up-staging at final excision that “would have prompted discussion of alternate surgical treatment such as SLN biopsy or wider surgical margins,” the team said.

Of the 89 transected pT1a melanomas identified, 47.1% with gross residual tumor or pigment on preoperative physical examination were up-staged following excision versus 6.9% with no remaining pigment or tumor prior to surgery (P < .01).

Broadly transected tumors were up-staged in 21.7% of cases versus 4.9% of focally transected tumors (P = .038). The average increase in Breslow depth for broadly transected tumors was 1.03 mm versus 0.03 mm for focally transected lesions (P = .04).

Shave biopsies, ulceration, and lack of concern for melanoma at the initial biopsy were among the factors associated with a higher risk of transection.

Superficial spreading melanoma was the most common subtype. Tumors were evenly distributed between the head, neck, and extremities. The average Breslow depth was 1.51 mm, and the majority of tumors were pT1a or pT2a.

The review excluded melanoma in situ, recurrences, metastases, noncutaneous melanomas, and biopsies where deep margin status was unknown.

There was no funding for the study, and Dr. Duncan and Dr. Patel had no relevant disclosures.

aotto@mdedge.com

The first multinational, phase 3, placebo-controlled trial conducted with intravenous immunoglobulin therapy (IVIg) for dermatomyositis has confirmed significant efficacy and acceptable safety, according to data presented at the opening plenary abstract session of the annual European Congress of Rheumatology.

At the week 16 evaluation of the trial, called ProDERM, the response rates were 78.7% and 43.8% (P = .0008) for active therapy and placebo, respectively, reported Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh.

ProDERM is a “much-awaited study,” according to session moderator Hendrik Schulze-Koops, MD, PhD, of the division of rheumatology and clinical immunology at Ludwig Maximilian University of Munich (Germany). He was not involved in the study.

“We all have been doing what we have been doing,” Dr. Schulze-Koops said, referring to the use of IVIg for the control of dermatomyositis, “but we had no evidence for support.”

This statement could apply not only to IVIg, which has long been listed among treatment options by the Myositis Association despite the absence of controlled studies, but also to most immunosuppressive therapies and other options used for this challenging disease.

The proprietary IVIg employed in this study, Octagam 10%, has been approved in the United States for the treatment of chronic immune thrombocytopenic purpura. Its manufacturer, Octagam, plans to file a supplemental new drug application with the Food and Drug Administration for the treatment of dermatomyositis. The agent is already approved for dermatomyositis by the European Medicines Agency, according to Dr. Aggarwal.

Multiple response criteria favor IVIg

In the trial, 95 patients with dermatomyositis were randomized to 2 g/kg of IVIg (Octagam 10%) or placebo administered every 4 weeks. In a subsequent open-label extension study in which patients on placebo were switched to active therapy, the same every-4-week treatment schedule was used. The patients’ mean age was 53; 75% were women, and 92% were White.

The primary endpoint was at least minimal improvement on 2016 ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) myositis response criteria, defined as a 20-point or greater gain in the Total Improvement Score (TIS) and no clinical worsening at two consecutive visits. But IVIg also provided a large relative benefit over placebo using more rigorous definitions of improvement. For moderate improvement, defined as at least a 40-point TIS improvement, there was a 45.2% relative advantage for IVIg over placebo (68.1% vs. 22.9%; P < .0001). For major improvement, defined as at least a 60-point TIS improvement, the relative advantage was 23.6% (31.9% vs. 8.3%; P < .0062).

At 16 weeks, the mean TIS score was more than twice as high in those receiving IVIg than in those randomized to placebo (48.4 vs. 21.6). At that point, an open-label extension was initiated. Those in the IVIg group were permitted to remain on therapy for an additional 24 weeks if they had not worsened in the blinded phase.

The mean TIS score in the IVIg group continued to rise during the extension phase. By 12 weeks in this phase, it reached 54.0. Over the same period, mean TIS scores climbed steeply among the placebo-treated patients who had switched to active therapy, reaching 44.4.

At the end of 24 weeks of the extension trial, when patients initiated on IVIg had been on active therapy for 40 weeks, the mean TIS score advantage of starting on IVIg rather than placebo was relatively modest (55.4 vs. 51.1).
 

Benefit is significant for skin and muscle

Changes in the two major components of dermatomyositis were tracked individually. For skin symptoms, patients were evaluated with the Cutaneous Dermatomyositis Disease Areas and Severity Index (CDASI). For muscle involvement, symptoms were evaluated with the 8-item Manual Muscle Testing (MMT-8) tool.

“The effects of IVIg on the muscle and the skin were both highly statistically significant,” Dr. Aggarwal reported. He said the CDASI score was reduced by almost half at the end of 16 weeks among those treated with IVIg relative to those treated with placebo. Improvement in MMT-8 scores were also clinically as well as statistically significant.

The IVIg therapy was well tolerated. The most common adverse effects in this study, like those reported with IVIg when used to treat other diseases, were headache, pyrexia, and nausea, but Dr. Aggarwal reported that these were generally mild.

Serious adverse events, particularly thromboembolism, did occur over the course of the study, but the rate of events was only slightly higher in the group receiving active therapy (5.8% vs. 4.2%).

Patients who entered the study were permitted to remain on most immunosuppressive therapies, such as methotrexate, mycophenolate, tacrolimus, and glucocorticoids. Dr. Aggarwal said that the majority of patients were taking a glucocorticoid and at least one nonglucocorticoid immunosuppressant.

Effect on associated conditions is planned

The data from this trial have not yet been analyzed for the impact of IVIg on conditions that occur frequently in association with dermatomyositis, such as interstitial lung disease (ILD) and dysphagia, but Dr. Aggarwal reported that there are plans to do so. Although severe ILD was a trial exclusion, the presence of mild to moderate ILD and dysphagia were evaluated at baseline, so the impact of treatment can be assessed.

There are also plans to evaluate how the presence or absence of myositis-specific antibodies, which were also evaluated at baseline, affected response to IVIg.

Dr. Aggarwal has financial relationships with more than 15 pharmaceutical companies, including Octapharma, which provided financial support for this trial. Dr. Schulze-Koops reported no relevant potential conflicts of interest.

The first multinational, phase 3, placebo-controlled trial conducted with intravenous immunoglobulin therapy (IVIg) for dermatomyositis has confirmed significant efficacy and acceptable safety, according to data presented at the opening plenary abstract session of the annual European Congress of Rheumatology.

At the week 16 evaluation of the trial, called ProDERM, the response rates were 78.7% and 43.8% (P = .0008) for active therapy and placebo, respectively, reported Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh.

ProDERM is a “much-awaited study,” according to session moderator Hendrik Schulze-Koops, MD, PhD, of the division of rheumatology and clinical immunology at Ludwig Maximilian University of Munich (Germany). He was not involved in the study.

“We all have been doing what we have been doing,” Dr. Schulze-Koops said, referring to the use of IVIg for the control of dermatomyositis, “but we had no evidence for support.”

This statement could apply not only to IVIg, which has long been listed among treatment options by the Myositis Association despite the absence of controlled studies, but also to most immunosuppressive therapies and other options used for this challenging disease.

The proprietary IVIg employed in this study, Octagam 10%, has been approved in the United States for the treatment of chronic immune thrombocytopenic purpura. Its manufacturer, Octagam, plans to file a supplemental new drug application with the Food and Drug Administration for the treatment of dermatomyositis. The agent is already approved for dermatomyositis by the European Medicines Agency, according to Dr. Aggarwal.

Multiple response criteria favor IVIg

In the trial, 95 patients with dermatomyositis were randomized to 2 g/kg of IVIg (Octagam 10%) or placebo administered every 4 weeks. In a subsequent open-label extension study in which patients on placebo were switched to active therapy, the same every-4-week treatment schedule was used. The patients’ mean age was 53; 75% were women, and 92% were White.

The primary endpoint was at least minimal improvement on 2016 ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) myositis response criteria, defined as a 20-point or greater gain in the Total Improvement Score (TIS) and no clinical worsening at two consecutive visits. But IVIg also provided a large relative benefit over placebo using more rigorous definitions of improvement. For moderate improvement, defined as at least a 40-point TIS improvement, there was a 45.2% relative advantage for IVIg over placebo (68.1% vs. 22.9%; P < .0001). For major improvement, defined as at least a 60-point TIS improvement, the relative advantage was 23.6% (31.9% vs. 8.3%; P < .0062).

At 16 weeks, the mean TIS score was more than twice as high in those receiving IVIg than in those randomized to placebo (48.4 vs. 21.6). At that point, an open-label extension was initiated. Those in the IVIg group were permitted to remain on therapy for an additional 24 weeks if they had not worsened in the blinded phase.

The mean TIS score in the IVIg group continued to rise during the extension phase. By 12 weeks in this phase, it reached 54.0. Over the same period, mean TIS scores climbed steeply among the placebo-treated patients who had switched to active therapy, reaching 44.4.

At the end of 24 weeks of the extension trial, when patients initiated on IVIg had been on active therapy for 40 weeks, the mean TIS score advantage of starting on IVIg rather than placebo was relatively modest (55.4 vs. 51.1).
 

Benefit is significant for skin and muscle

Changes in the two major components of dermatomyositis were tracked individually. For skin symptoms, patients were evaluated with the Cutaneous Dermatomyositis Disease Areas and Severity Index (CDASI). For muscle involvement, symptoms were evaluated with the 8-item Manual Muscle Testing (MMT-8) tool.

“The effects of IVIg on the muscle and the skin were both highly statistically significant,” Dr. Aggarwal reported. He said the CDASI score was reduced by almost half at the end of 16 weeks among those treated with IVIg relative to those treated with placebo. Improvement in MMT-8 scores were also clinically as well as statistically significant.

The IVIg therapy was well tolerated. The most common adverse effects in this study, like those reported with IVIg when used to treat other diseases, were headache, pyrexia, and nausea, but Dr. Aggarwal reported that these were generally mild.

Serious adverse events, particularly thromboembolism, did occur over the course of the study, but the rate of events was only slightly higher in the group receiving active therapy (5.8% vs. 4.2%).

Patients who entered the study were permitted to remain on most immunosuppressive therapies, such as methotrexate, mycophenolate, tacrolimus, and glucocorticoids. Dr. Aggarwal said that the majority of patients were taking a glucocorticoid and at least one nonglucocorticoid immunosuppressant.

Effect on associated conditions is planned

The data from this trial have not yet been analyzed for the impact of IVIg on conditions that occur frequently in association with dermatomyositis, such as interstitial lung disease (ILD) and dysphagia, but Dr. Aggarwal reported that there are plans to do so. Although severe ILD was a trial exclusion, the presence of mild to moderate ILD and dysphagia were evaluated at baseline, so the impact of treatment can be assessed.

There are also plans to evaluate how the presence or absence of myositis-specific antibodies, which were also evaluated at baseline, affected response to IVIg.

Dr. Aggarwal has financial relationships with more than 15 pharmaceutical companies, including Octapharma, which provided financial support for this trial. Dr. Schulze-Koops reported no relevant potential conflicts of interest.

The first multinational, phase 3, placebo-controlled trial conducted with intravenous immunoglobulin therapy (IVIg) for dermatomyositis has confirmed significant efficacy and acceptable safety, according to data presented at the opening plenary abstract session of the annual European Congress of Rheumatology.

At the week 16 evaluation of the trial, called ProDERM, the response rates were 78.7% and 43.8% (P = .0008) for active therapy and placebo, respectively, reported Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh.

ProDERM is a “much-awaited study,” according to session moderator Hendrik Schulze-Koops, MD, PhD, of the division of rheumatology and clinical immunology at Ludwig Maximilian University of Munich (Germany). He was not involved in the study.

“We all have been doing what we have been doing,” Dr. Schulze-Koops said, referring to the use of IVIg for the control of dermatomyositis, “but we had no evidence for support.”

This statement could apply not only to IVIg, which has long been listed among treatment options by the Myositis Association despite the absence of controlled studies, but also to most immunosuppressive therapies and other options used for this challenging disease.

The proprietary IVIg employed in this study, Octagam 10%, has been approved in the United States for the treatment of chronic immune thrombocytopenic purpura. Its manufacturer, Octagam, plans to file a supplemental new drug application with the Food and Drug Administration for the treatment of dermatomyositis. The agent is already approved for dermatomyositis by the European Medicines Agency, according to Dr. Aggarwal.

Multiple response criteria favor IVIg

In the trial, 95 patients with dermatomyositis were randomized to 2 g/kg of IVIg (Octagam 10%) or placebo administered every 4 weeks. In a subsequent open-label extension study in which patients on placebo were switched to active therapy, the same every-4-week treatment schedule was used. The patients’ mean age was 53; 75% were women, and 92% were White.

The primary endpoint was at least minimal improvement on 2016 ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) myositis response criteria, defined as a 20-point or greater gain in the Total Improvement Score (TIS) and no clinical worsening at two consecutive visits. But IVIg also provided a large relative benefit over placebo using more rigorous definitions of improvement. For moderate improvement, defined as at least a 40-point TIS improvement, there was a 45.2% relative advantage for IVIg over placebo (68.1% vs. 22.9%; P < .0001). For major improvement, defined as at least a 60-point TIS improvement, the relative advantage was 23.6% (31.9% vs. 8.3%; P < .0062).

At 16 weeks, the mean TIS score was more than twice as high in those receiving IVIg than in those randomized to placebo (48.4 vs. 21.6). At that point, an open-label extension was initiated. Those in the IVIg group were permitted to remain on therapy for an additional 24 weeks if they had not worsened in the blinded phase.

The mean TIS score in the IVIg group continued to rise during the extension phase. By 12 weeks in this phase, it reached 54.0. Over the same period, mean TIS scores climbed steeply among the placebo-treated patients who had switched to active therapy, reaching 44.4.

At the end of 24 weeks of the extension trial, when patients initiated on IVIg had been on active therapy for 40 weeks, the mean TIS score advantage of starting on IVIg rather than placebo was relatively modest (55.4 vs. 51.1).
 

Benefit is significant for skin and muscle

Changes in the two major components of dermatomyositis were tracked individually. For skin symptoms, patients were evaluated with the Cutaneous Dermatomyositis Disease Areas and Severity Index (CDASI). For muscle involvement, symptoms were evaluated with the 8-item Manual Muscle Testing (MMT-8) tool.

“The effects of IVIg on the muscle and the skin were both highly statistically significant,” Dr. Aggarwal reported. He said the CDASI score was reduced by almost half at the end of 16 weeks among those treated with IVIg relative to those treated with placebo. Improvement in MMT-8 scores were also clinically as well as statistically significant.

The IVIg therapy was well tolerated. The most common adverse effects in this study, like those reported with IVIg when used to treat other diseases, were headache, pyrexia, and nausea, but Dr. Aggarwal reported that these were generally mild.

Serious adverse events, particularly thromboembolism, did occur over the course of the study, but the rate of events was only slightly higher in the group receiving active therapy (5.8% vs. 4.2%).

Patients who entered the study were permitted to remain on most immunosuppressive therapies, such as methotrexate, mycophenolate, tacrolimus, and glucocorticoids. Dr. Aggarwal said that the majority of patients were taking a glucocorticoid and at least one nonglucocorticoid immunosuppressant.

Effect on associated conditions is planned

The data from this trial have not yet been analyzed for the impact of IVIg on conditions that occur frequently in association with dermatomyositis, such as interstitial lung disease (ILD) and dysphagia, but Dr. Aggarwal reported that there are plans to do so. Although severe ILD was a trial exclusion, the presence of mild to moderate ILD and dysphagia were evaluated at baseline, so the impact of treatment can be assessed.

There are also plans to evaluate how the presence or absence of myositis-specific antibodies, which were also evaluated at baseline, affected response to IVIg.

Dr. Aggarwal has financial relationships with more than 15 pharmaceutical companies, including Octapharma, which provided financial support for this trial. Dr. Schulze-Koops reported no relevant potential conflicts of interest.

The Food and Drug Administration has approved the interleukin-17 inhibitor secukinumab (Cosentyx) for the treatment of moderate to severe plaque psoriasis in pediatric patients aged 6 years and older who are candidates for systemic therapy or phototherapy. The expanded indication marks the first time the drug has been available for a pediatric population in the United States.

Children with plaque psoriasis are often undertreated because of fear of side effects of therapies, according to Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco. “Now, more and more medicines are being tested for safety and efficacy in children, and we no longer have to rely on adult studies to inform treatment choices for children,” Dr. Cordoro told this news organization.

The FDA approval of secukinumab for children aged 6 and older with moderate to severe psoriasis “is a welcome addition to the therapeutic toolbox for pediatric psoriasis,” she said. “We’ve entered an era where severe pediatric psoriasis has become a condition that can be adequately controlled with minimal risk and with the convenience of intermittent injections. This has changed the playing field for these children and their families completely. Given the potential short- and long-term negative impact of chronic inflammation on the body of a growing child, we now have approved treatments that can safely offset the risks of undertreated severe psoriasis on the functional and psychological health of the child.”

The approved pediatric dosing for secukinumab is 75 mg or 150 mg depending on the child’s weight at the time of dosing, and it is administered by subcutaneous injection every 4 weeks after an initial loading regimen. According to a press release from Novartis, the FDA approval came on the heels of two phase 3 studies that evaluated the use of secukinumab in children aged 6 to younger than 18 years with plaque psoriasis. The first was a 52-week, randomized, double-blind, placebo- and active-controlled study which included 162 children 6 years of age and older with severe plaque psoriasis. The doses evaluated were 75 mg for children who weighed less than 50 kg and 150 mg for those 50 kg or greater.

At week 12, the Psoriasis Area Severity Index (PASI)-75 response was 55% among children in the 75-mg dosing group vs. 10% in the placebo group and 86% in the 150-mg dosing group vs. 19% in the placebo group.

Meanwhile, the Investigator’s Global Assessment modified 2011 (IGA) “clear” response was achieved in 32% of children in the 75-mg dosing group vs. 5% in the placebo group and in 81% of children in the 150-mg dosing group vs. 5% in the placebo group. An IGA “almost clear” skin response was achieved in 81% of children in the 75-mg dosing group vs. 5% in the placebo group.

The second phase 3 study was a randomized open-label, 208-week trial of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis. According to the Novartis press release, the safety profile reported in both trials was consistent with the safety profile reported in adult plaque psoriasis trials and no new safety signals were observed. The updated prescribing information for secukinumab can be found here.

“When considering treatment with a systemic agent such as a biologic, it is important to consider objective measures of severity, such as extent of disease and involvement of joints but also subjective indicators of severity such as impact beyond the skin on psychological well-being,” Dr. Cordoro said in the interview. “Kids with psoriasis in visible locations may socially isolate themselves due to embarrassment or bullying. Therefore, the impact of moderate to severe psoriasis not only on overall health but on self-esteem and identity formation can be significant, and therefore adequately treating children of all ages to prevent the downstream negative consequences of childhood psoriasis is critical.”

Dr. Cordoro reported having no financial disclosures.

dbrunk@mdedge.com

The Food and Drug Administration has approved the interleukin-17 inhibitor secukinumab (Cosentyx) for the treatment of moderate to severe plaque psoriasis in pediatric patients aged 6 years and older who are candidates for systemic therapy or phototherapy. The expanded indication marks the first time the drug has been available for a pediatric population in the United States.

Children with plaque psoriasis are often undertreated because of fear of side effects of therapies, according to Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco. “Now, more and more medicines are being tested for safety and efficacy in children, and we no longer have to rely on adult studies to inform treatment choices for children,” Dr. Cordoro told this news organization.

The FDA approval of secukinumab for children aged 6 and older with moderate to severe psoriasis “is a welcome addition to the therapeutic toolbox for pediatric psoriasis,” she said. “We’ve entered an era where severe pediatric psoriasis has become a condition that can be adequately controlled with minimal risk and with the convenience of intermittent injections. This has changed the playing field for these children and their families completely. Given the potential short- and long-term negative impact of chronic inflammation on the body of a growing child, we now have approved treatments that can safely offset the risks of undertreated severe psoriasis on the functional and psychological health of the child.”

The approved pediatric dosing for secukinumab is 75 mg or 150 mg depending on the child’s weight at the time of dosing, and it is administered by subcutaneous injection every 4 weeks after an initial loading regimen. According to a press release from Novartis, the FDA approval came on the heels of two phase 3 studies that evaluated the use of secukinumab in children aged 6 to younger than 18 years with plaque psoriasis. The first was a 52-week, randomized, double-blind, placebo- and active-controlled study which included 162 children 6 years of age and older with severe plaque psoriasis. The doses evaluated were 75 mg for children who weighed less than 50 kg and 150 mg for those 50 kg or greater.

At week 12, the Psoriasis Area Severity Index (PASI)-75 response was 55% among children in the 75-mg dosing group vs. 10% in the placebo group and 86% in the 150-mg dosing group vs. 19% in the placebo group.

Meanwhile, the Investigator’s Global Assessment modified 2011 (IGA) “clear” response was achieved in 32% of children in the 75-mg dosing group vs. 5% in the placebo group and in 81% of children in the 150-mg dosing group vs. 5% in the placebo group. An IGA “almost clear” skin response was achieved in 81% of children in the 75-mg dosing group vs. 5% in the placebo group.

The second phase 3 study was a randomized open-label, 208-week trial of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis. According to the Novartis press release, the safety profile reported in both trials was consistent with the safety profile reported in adult plaque psoriasis trials and no new safety signals were observed. The updated prescribing information for secukinumab can be found here.

“When considering treatment with a systemic agent such as a biologic, it is important to consider objective measures of severity, such as extent of disease and involvement of joints but also subjective indicators of severity such as impact beyond the skin on psychological well-being,” Dr. Cordoro said in the interview. “Kids with psoriasis in visible locations may socially isolate themselves due to embarrassment or bullying. Therefore, the impact of moderate to severe psoriasis not only on overall health but on self-esteem and identity formation can be significant, and therefore adequately treating children of all ages to prevent the downstream negative consequences of childhood psoriasis is critical.”

Dr. Cordoro reported having no financial disclosures.

dbrunk@mdedge.com

The Food and Drug Administration has approved the interleukin-17 inhibitor secukinumab (Cosentyx) for the treatment of moderate to severe plaque psoriasis in pediatric patients aged 6 years and older who are candidates for systemic therapy or phototherapy. The expanded indication marks the first time the drug has been available for a pediatric population in the United States.

Children with plaque psoriasis are often undertreated because of fear of side effects of therapies, according to Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco. “Now, more and more medicines are being tested for safety and efficacy in children, and we no longer have to rely on adult studies to inform treatment choices for children,” Dr. Cordoro told this news organization.

The FDA approval of secukinumab for children aged 6 and older with moderate to severe psoriasis “is a welcome addition to the therapeutic toolbox for pediatric psoriasis,” she said. “We’ve entered an era where severe pediatric psoriasis has become a condition that can be adequately controlled with minimal risk and with the convenience of intermittent injections. This has changed the playing field for these children and their families completely. Given the potential short- and long-term negative impact of chronic inflammation on the body of a growing child, we now have approved treatments that can safely offset the risks of undertreated severe psoriasis on the functional and psychological health of the child.”

The approved pediatric dosing for secukinumab is 75 mg or 150 mg depending on the child’s weight at the time of dosing, and it is administered by subcutaneous injection every 4 weeks after an initial loading regimen. According to a press release from Novartis, the FDA approval came on the heels of two phase 3 studies that evaluated the use of secukinumab in children aged 6 to younger than 18 years with plaque psoriasis. The first was a 52-week, randomized, double-blind, placebo- and active-controlled study which included 162 children 6 years of age and older with severe plaque psoriasis. The doses evaluated were 75 mg for children who weighed less than 50 kg and 150 mg for those 50 kg or greater.

At week 12, the Psoriasis Area Severity Index (PASI)-75 response was 55% among children in the 75-mg dosing group vs. 10% in the placebo group and 86% in the 150-mg dosing group vs. 19% in the placebo group.

Meanwhile, the Investigator’s Global Assessment modified 2011 (IGA) “clear” response was achieved in 32% of children in the 75-mg dosing group vs. 5% in the placebo group and in 81% of children in the 150-mg dosing group vs. 5% in the placebo group. An IGA “almost clear” skin response was achieved in 81% of children in the 75-mg dosing group vs. 5% in the placebo group.

The second phase 3 study was a randomized open-label, 208-week trial of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis. According to the Novartis press release, the safety profile reported in both trials was consistent with the safety profile reported in adult plaque psoriasis trials and no new safety signals were observed. The updated prescribing information for secukinumab can be found here.

“When considering treatment with a systemic agent such as a biologic, it is important to consider objective measures of severity, such as extent of disease and involvement of joints but also subjective indicators of severity such as impact beyond the skin on psychological well-being,” Dr. Cordoro said in the interview. “Kids with psoriasis in visible locations may socially isolate themselves due to embarrassment or bullying. Therefore, the impact of moderate to severe psoriasis not only on overall health but on self-esteem and identity formation can be significant, and therefore adequately treating children of all ages to prevent the downstream negative consequences of childhood psoriasis is critical.”

Dr. Cordoro reported having no financial disclosures.

dbrunk@mdedge.com