Dermatology

A punch biopsy of the markedly erythematous lateral edge helped to confirm this as tumid lupus erythematosus (TLE), a rare subtype of chronic cutaneous lupus erythematosus. TLE occurs in men and women of all ages. Annular or arcuate patches and plaques most often arise on the face, trunk, extremities, and V of the neck after sun exposure. However, as in this case, plaques may appear in areas covered by clothing. Plaques generally do not itch or hurt, but their presence can be alarming.

Annular and arcuate plaques raise a complex differential diagnosis including common conditions such as urticaria and tinea corporis, as well as more uncommon disorders such as erythema annulare centrifugum and lymphoma cutis. Unlike tinea corporis and erythema annulare centrifugum, there is very little, if any, scaling of the superficial epidermis. Plaques heal without scarring or changes to skin pigmentation.

Multiple punch biopsies of affected areas are key to a proper diagnosis. Patients with confirmed TLE should undergo antinuclear antibody testing to rule out systemic lupus erythematosus, although the vast majority will have normal results.

Treatment includes potent or ultrapotent topical steroids for the trunk and extremities, and mid- to low-potency steroids for intertriginous areas or the face. Systemic immunomodulators with hydroxychloroquine are used as first-line treatment for more extensive disease.

In this case, the patient had a normal antinuclear antibody titer and was treated with topical betamethasone dipropionate augmented 0.05% cream bid for 2 weeks, which led to complete clearance. She experienced a flare-up a year later and was retreated with the same results.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

A punch biopsy of the markedly erythematous lateral edge helped to confirm this as tumid lupus erythematosus (TLE), a rare subtype of chronic cutaneous lupus erythematosus. TLE occurs in men and women of all ages. Annular or arcuate patches and plaques most often arise on the face, trunk, extremities, and V of the neck after sun exposure. However, as in this case, plaques may appear in areas covered by clothing. Plaques generally do not itch or hurt, but their presence can be alarming.

Annular and arcuate plaques raise a complex differential diagnosis including common conditions such as urticaria and tinea corporis, as well as more uncommon disorders such as erythema annulare centrifugum and lymphoma cutis. Unlike tinea corporis and erythema annulare centrifugum, there is very little, if any, scaling of the superficial epidermis. Plaques heal without scarring or changes to skin pigmentation.

Multiple punch biopsies of affected areas are key to a proper diagnosis. Patients with confirmed TLE should undergo antinuclear antibody testing to rule out systemic lupus erythematosus, although the vast majority will have normal results.

Treatment includes potent or ultrapotent topical steroids for the trunk and extremities, and mid- to low-potency steroids for intertriginous areas or the face. Systemic immunomodulators with hydroxychloroquine are used as first-line treatment for more extensive disease.

In this case, the patient had a normal antinuclear antibody titer and was treated with topical betamethasone dipropionate augmented 0.05% cream bid for 2 weeks, which led to complete clearance. She experienced a flare-up a year later and was retreated with the same results.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

A punch biopsy of the markedly erythematous lateral edge helped to confirm this as tumid lupus erythematosus (TLE), a rare subtype of chronic cutaneous lupus erythematosus. TLE occurs in men and women of all ages. Annular or arcuate patches and plaques most often arise on the face, trunk, extremities, and V of the neck after sun exposure. However, as in this case, plaques may appear in areas covered by clothing. Plaques generally do not itch or hurt, but their presence can be alarming.

Annular and arcuate plaques raise a complex differential diagnosis including common conditions such as urticaria and tinea corporis, as well as more uncommon disorders such as erythema annulare centrifugum and lymphoma cutis. Unlike tinea corporis and erythema annulare centrifugum, there is very little, if any, scaling of the superficial epidermis. Plaques heal without scarring or changes to skin pigmentation.

Multiple punch biopsies of affected areas are key to a proper diagnosis. Patients with confirmed TLE should undergo antinuclear antibody testing to rule out systemic lupus erythematosus, although the vast majority will have normal results.

Treatment includes potent or ultrapotent topical steroids for the trunk and extremities, and mid- to low-potency steroids for intertriginous areas or the face. Systemic immunomodulators with hydroxychloroquine are used as first-line treatment for more extensive disease.

In this case, the patient had a normal antinuclear antibody titer and was treated with topical betamethasone dipropionate augmented 0.05% cream bid for 2 weeks, which led to complete clearance. She experienced a flare-up a year later and was retreated with the same results.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The most effective initial step for clearing atopic dermatitis in infants and young children involves daily bathing, followed by immediate application of a moisturizer, topical steroid, or both, according to an expert speaking at the virtual annual Coastal Dermatology Symposium.

FotoDuets/iStock/Getty Images

“If they are really severe, you can do it twice-daily, but there are several studies that show there is not a huge benefit of twice-daily over once-daily,” said Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland.

He called this technique “soak-and-smear.” The “smear” is performed immediately after the bath when the skin is still damp, he said. When clearing is the goal, and the child has moderate to severe atopic dermatitis (AD), 0.1% triamcinolone or a similar medium potency topical steroid can be applied, and after clearing, the steroid can be switched for a moisturizer, according to Dr. Simpson.

Rather than restricting application to areas of greatest skin involvement, “put it all over,” he advised.

The clearing regimen should be continued “for a couple of more days” after the lesions have resolved, with a return visit in about a week to confirm clearing and reinforce the next steps for keeping patients clear, he added.

The next steps depend on severity. According to Dr. Simpson, severity is defined less by the extent of skin involvement at the baseline examination than the speed at which symptoms return.

For those with only mild symptoms after an extended period of clearing, moisturizer might be sufficient to prevent a significant relapse. For children with a more rapid relapse, it will be necessary to reintroduce topical steroid either every day, every other day, or twice per week.

Whether with moisturizer or with topical steroids, the soak-and-smear technique has now been validated in a recently published crossover randomized trial.

In the trial, children aged 6 months to 11 years, with moderate to severe AD, were randomized to a twice-daily bath, called the “wet method,” versus a twice-weekly bath, called the “dry method.” Both groups received a cleanser and moisturizer along with a low-potency topical steroid as needed.

After 2 weeks, the 40 evaluable patients were crossed over to the opposite bathing technique. The wet, or soak-and-smear approach, was associated with a highly significant reduction in the primary endpoint of SCORing Atopic Dermatitis (SCORAD) index, compared with the dry method (95% confidence interval, 14.9-27.6; P less than .0001). In a secondary analysis, this translated into a 30% relative reduction in favor of the wet method.

In addition, there was improvement in a caregiver assessment of the Atopic Dermatitis Quickscore (ADQ). These data show that “twice-daily baths with topical steroids and moisturizer can help in more moderate to severe population,” said Dr. Simpson, who noted that he has participated in open-label studies with the same soak-and-smear technique that have produced similar results.

Once children are clear, Dr. Simpson recommends a maintenance strategy individualized for severity. In many cases, this will involve moisturizers applied after the bath, supplemented intermittently, such as once or twice per week, with topical steroids. However, if parents find themselves resorting to daily steroids to maintain control, “that’s when you incorporate the TCIs [topical calcineurin inhibitors].”

TCIs “can help you stay at twice-per-week topical steroids,” Dr. Simpson said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

TCIs also help patients avoid steroid withdrawal, a particularly common phenomenon when topical steroids are applied repeatedly to the face. He recommended a proactive approach. By applying TCIs to areas where skin lesions frequently recur, such as the eyelids, flares can often be prevented.

Repeated applications of TCIs “is perfectly safe and effective, and there are many studies that show proactive treatment is very effective and can prevent you from having to use too much topical steroids” or move to a systemic steroid, Dr. Simpson said.

These steps have been highly effective for sustained control even in challenging cases of AD, but he emphasized the importance of explaining the rationale to parents and eliciting their adherence to these treatment steps. Writing out the instructions will reduce confusion and help parents keep their children clear, he added.

Lawrence F. Eichenfield, MD, professor of pediatrics and dermatology at the University of California, San Diego, agreed that this recently published crossover trial has been helpful in counseling parents about how to manage AD in their children.

The most effective initial step for clearing atopic dermatitis in infants and young children involves daily bathing, followed by immediate application of a moisturizer, topical steroid, or both, according to an expert speaking at the virtual annual Coastal Dermatology Symposium.

FotoDuets/iStock/Getty Images

“If they are really severe, you can do it twice-daily, but there are several studies that show there is not a huge benefit of twice-daily over once-daily,” said Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland.

He called this technique “soak-and-smear.” The “smear” is performed immediately after the bath when the skin is still damp, he said. When clearing is the goal, and the child has moderate to severe atopic dermatitis (AD), 0.1% triamcinolone or a similar medium potency topical steroid can be applied, and after clearing, the steroid can be switched for a moisturizer, according to Dr. Simpson.

Rather than restricting application to areas of greatest skin involvement, “put it all over,” he advised.

The clearing regimen should be continued “for a couple of more days” after the lesions have resolved, with a return visit in about a week to confirm clearing and reinforce the next steps for keeping patients clear, he added.

The next steps depend on severity. According to Dr. Simpson, severity is defined less by the extent of skin involvement at the baseline examination than the speed at which symptoms return.

For those with only mild symptoms after an extended period of clearing, moisturizer might be sufficient to prevent a significant relapse. For children with a more rapid relapse, it will be necessary to reintroduce topical steroid either every day, every other day, or twice per week.

Whether with moisturizer or with topical steroids, the soak-and-smear technique has now been validated in a recently published crossover randomized trial.

In the trial, children aged 6 months to 11 years, with moderate to severe AD, were randomized to a twice-daily bath, called the “wet method,” versus a twice-weekly bath, called the “dry method.” Both groups received a cleanser and moisturizer along with a low-potency topical steroid as needed.

After 2 weeks, the 40 evaluable patients were crossed over to the opposite bathing technique. The wet, or soak-and-smear approach, was associated with a highly significant reduction in the primary endpoint of SCORing Atopic Dermatitis (SCORAD) index, compared with the dry method (95% confidence interval, 14.9-27.6; P less than .0001). In a secondary analysis, this translated into a 30% relative reduction in favor of the wet method.

In addition, there was improvement in a caregiver assessment of the Atopic Dermatitis Quickscore (ADQ). These data show that “twice-daily baths with topical steroids and moisturizer can help in more moderate to severe population,” said Dr. Simpson, who noted that he has participated in open-label studies with the same soak-and-smear technique that have produced similar results.

Once children are clear, Dr. Simpson recommends a maintenance strategy individualized for severity. In many cases, this will involve moisturizers applied after the bath, supplemented intermittently, such as once or twice per week, with topical steroids. However, if parents find themselves resorting to daily steroids to maintain control, “that’s when you incorporate the TCIs [topical calcineurin inhibitors].”

TCIs “can help you stay at twice-per-week topical steroids,” Dr. Simpson said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

TCIs also help patients avoid steroid withdrawal, a particularly common phenomenon when topical steroids are applied repeatedly to the face. He recommended a proactive approach. By applying TCIs to areas where skin lesions frequently recur, such as the eyelids, flares can often be prevented.

Repeated applications of TCIs “is perfectly safe and effective, and there are many studies that show proactive treatment is very effective and can prevent you from having to use too much topical steroids” or move to a systemic steroid, Dr. Simpson said.

These steps have been highly effective for sustained control even in challenging cases of AD, but he emphasized the importance of explaining the rationale to parents and eliciting their adherence to these treatment steps. Writing out the instructions will reduce confusion and help parents keep their children clear, he added.

Lawrence F. Eichenfield, MD, professor of pediatrics and dermatology at the University of California, San Diego, agreed that this recently published crossover trial has been helpful in counseling parents about how to manage AD in their children.

The most effective initial step for clearing atopic dermatitis in infants and young children involves daily bathing, followed by immediate application of a moisturizer, topical steroid, or both, according to an expert speaking at the virtual annual Coastal Dermatology Symposium.

FotoDuets/iStock/Getty Images

“If they are really severe, you can do it twice-daily, but there are several studies that show there is not a huge benefit of twice-daily over once-daily,” said Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland.

He called this technique “soak-and-smear.” The “smear” is performed immediately after the bath when the skin is still damp, he said. When clearing is the goal, and the child has moderate to severe atopic dermatitis (AD), 0.1% triamcinolone or a similar medium potency topical steroid can be applied, and after clearing, the steroid can be switched for a moisturizer, according to Dr. Simpson.

Rather than restricting application to areas of greatest skin involvement, “put it all over,” he advised.

The clearing regimen should be continued “for a couple of more days” after the lesions have resolved, with a return visit in about a week to confirm clearing and reinforce the next steps for keeping patients clear, he added.

The next steps depend on severity. According to Dr. Simpson, severity is defined less by the extent of skin involvement at the baseline examination than the speed at which symptoms return.

For those with only mild symptoms after an extended period of clearing, moisturizer might be sufficient to prevent a significant relapse. For children with a more rapid relapse, it will be necessary to reintroduce topical steroid either every day, every other day, or twice per week.

Whether with moisturizer or with topical steroids, the soak-and-smear technique has now been validated in a recently published crossover randomized trial.

In the trial, children aged 6 months to 11 years, with moderate to severe AD, were randomized to a twice-daily bath, called the “wet method,” versus a twice-weekly bath, called the “dry method.” Both groups received a cleanser and moisturizer along with a low-potency topical steroid as needed.

After 2 weeks, the 40 evaluable patients were crossed over to the opposite bathing technique. The wet, or soak-and-smear approach, was associated with a highly significant reduction in the primary endpoint of SCORing Atopic Dermatitis (SCORAD) index, compared with the dry method (95% confidence interval, 14.9-27.6; P less than .0001). In a secondary analysis, this translated into a 30% relative reduction in favor of the wet method.

In addition, there was improvement in a caregiver assessment of the Atopic Dermatitis Quickscore (ADQ). These data show that “twice-daily baths with topical steroids and moisturizer can help in more moderate to severe population,” said Dr. Simpson, who noted that he has participated in open-label studies with the same soak-and-smear technique that have produced similar results.

Once children are clear, Dr. Simpson recommends a maintenance strategy individualized for severity. In many cases, this will involve moisturizers applied after the bath, supplemented intermittently, such as once or twice per week, with topical steroids. However, if parents find themselves resorting to daily steroids to maintain control, “that’s when you incorporate the TCIs [topical calcineurin inhibitors].”

TCIs “can help you stay at twice-per-week topical steroids,” Dr. Simpson said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

TCIs also help patients avoid steroid withdrawal, a particularly common phenomenon when topical steroids are applied repeatedly to the face. He recommended a proactive approach. By applying TCIs to areas where skin lesions frequently recur, such as the eyelids, flares can often be prevented.

Repeated applications of TCIs “is perfectly safe and effective, and there are many studies that show proactive treatment is very effective and can prevent you from having to use too much topical steroids” or move to a systemic steroid, Dr. Simpson said.

These steps have been highly effective for sustained control even in challenging cases of AD, but he emphasized the importance of explaining the rationale to parents and eliciting their adherence to these treatment steps. Writing out the instructions will reduce confusion and help parents keep their children clear, he added.

Lawrence F. Eichenfield, MD, professor of pediatrics and dermatology at the University of California, San Diego, agreed that this recently published crossover trial has been helpful in counseling parents about how to manage AD in their children.

Last month, the American College of Rheumatology joined with 11 other medical associations and disease societies asking health insurance giant UnitedHealthcare (UHC) to not proceed with its proposed copay accumulator medical benefit program.

Copay accumulators are policies adopted by insurance companies or their pharmacy benefit managers to exclude patient copayment assistance programs for high-cost drugs, which are promulgated by the drug manufacturers, from being applied to a patient’s annual deductibles or out-of-pocket maximums. The manufacturer’s copay assistance, such as in the form of coupons, is designed to minimize the patient’s out-of-pocket costs. But insurers believe manufacturers will have no pressure to lower the prices of expensive specialty drugs unless patients are unable to afford them. Copay accumulators thus are aimed at giving insurers more leverage in negotiating prices for high-cost drugs.

UHC issued its new copay accumulator protocol for commercial individual and fully insured group plans in early October, effective Jan. 1, 2021, “in order to align employer costs for specialty medications with actual member out of pocket and deductibles,” according to the company’s announcement. In other words, patients will need to pay a higher share of the costs of these medications, said rheumatologist Christopher Phillips, MD, who chairs the Insurance Subcommittee of ACR’s Rheumatologic Care Committee. The annual price of biologic therapies for rheumatologic conditions ranges from $22,000 to $44,000, according to a recent press release from ACR.

The copay accumulator will negate the benefits of manufacturers’ copayment assistance programs for the patient, shifting more of the cost to the patient. With patients being forced to pay a higher share of drug costs for expensive biologic treatments for rheumatoid arthritis, lupus, and other rheumatologic conditions, they’ll stop taking the treatments, Dr. Phillips said.

“In my solo rheumatology practice in Paducah, Kentucky, when I’ve seen this kind of program applied on the pharmacy benefit side, rather than the medical benefit side, almost uniformly patients stop taking the high-cost treatments.” That can lead to disease flares, complications, and permanent disability. The newer rheumatologic drugs can cost $500 to $1,000 per treatment, and in many cases, there’s no generic or lower-cost alternative, he says. “We see policies like this as sacrificing patients to the battle over high drug prices. It’s bad practice, bad for patient outcomes, and nobody – apart from the payer – benefits.”

In ACR’s 2020 Rheumatic Disease Patient Survey, nearly half of 1,109 online survey respondents who had rheumatic diseases reported out-of-pocket costs greater than $1,000 per year for treatment. An IQVIA report from 2016 found that one in four specialty brand prescriptions are abandoned during the deductible phase, three times the rate seen when there is no deductible.

In an Oct. 7 letter to UHC, the 12 groups acknowledged that the drugs targeted by the accumulator policy are expensive. “However, they are also vitally important for our patients.” In addition to the ACR, the organizations involved include the AIDS Institute, American Academy of Dermatology Association, American Academy of Neurology, American College of Gastroenterology, American Gastroenterological Association, American Kidney Fund, Arthritis Foundation, Association for Clinical Oncology, Cancer Support Community, Coalition of State Rheumatology Organizations, and National Multiple Sclerosis Society.

UHC did not reply to questions in time for publication.


 

First large-scale payer to try copay accumulator program

Under UHC’s proposed policy, providers will be required to use UHC’s portal to report payment information received from drug manufacturer copay assistance programs that are applied to patients’ cost share of these drugs through a complex, 14-step “coupon submission process” involving multiple technology interfaces. “My first oath as a physician is to do no harm to my patient. Many of us are concerned about making these reports, which could harm our patients and undermine the doctor-patient relationship,” Dr. Phillips said.

“If I don’t report, what happens? I don’t think we know the answer to that. Some of us may decide we need to part ways with UHC.” Others may decline to participate in the drug manufacturers’ coupon programs beyond simply informing patients that manufacturer assistance is available.

“We’ve watched these copay accumulator policies for several years,” he said. “Some of them are rather opaque, with names like ‘copay savings programs’ or ‘copay value programs.’ But we had not seen a large-scale payer try to do this until now. Let’s face it: If UHC’s policy goes through, you can count the days until we see it from others.”

The Department of Health & Human Services, in its May 2020 final federal “Notice of Benefit and Payment Parameters for 2021,” indicated that individual states have the responsibility to regulate copay accumulator programs. Five states have banned them or restricted their use for individual and small group health plans. Arizona, Illinois, Virginia, and West Virginia passed such laws in 2019, and Georgia did so earlier this year.

“In next year’s state legislative sessions, we’ll make it a priority to pursue similar laws in other states,” Dr. Phillips said. “I’d encourage rheumatologists to educate their patients on the issues and be active in advocating for them.”

Last month, the American College of Rheumatology joined with 11 other medical associations and disease societies asking health insurance giant UnitedHealthcare (UHC) to not proceed with its proposed copay accumulator medical benefit program.

Copay accumulators are policies adopted by insurance companies or their pharmacy benefit managers to exclude patient copayment assistance programs for high-cost drugs, which are promulgated by the drug manufacturers, from being applied to a patient’s annual deductibles or out-of-pocket maximums. The manufacturer’s copay assistance, such as in the form of coupons, is designed to minimize the patient’s out-of-pocket costs. But insurers believe manufacturers will have no pressure to lower the prices of expensive specialty drugs unless patients are unable to afford them. Copay accumulators thus are aimed at giving insurers more leverage in negotiating prices for high-cost drugs.

UHC issued its new copay accumulator protocol for commercial individual and fully insured group plans in early October, effective Jan. 1, 2021, “in order to align employer costs for specialty medications with actual member out of pocket and deductibles,” according to the company’s announcement. In other words, patients will need to pay a higher share of the costs of these medications, said rheumatologist Christopher Phillips, MD, who chairs the Insurance Subcommittee of ACR’s Rheumatologic Care Committee. The annual price of biologic therapies for rheumatologic conditions ranges from $22,000 to $44,000, according to a recent press release from ACR.

The copay accumulator will negate the benefits of manufacturers’ copayment assistance programs for the patient, shifting more of the cost to the patient. With patients being forced to pay a higher share of drug costs for expensive biologic treatments for rheumatoid arthritis, lupus, and other rheumatologic conditions, they’ll stop taking the treatments, Dr. Phillips said.

“In my solo rheumatology practice in Paducah, Kentucky, when I’ve seen this kind of program applied on the pharmacy benefit side, rather than the medical benefit side, almost uniformly patients stop taking the high-cost treatments.” That can lead to disease flares, complications, and permanent disability. The newer rheumatologic drugs can cost $500 to $1,000 per treatment, and in many cases, there’s no generic or lower-cost alternative, he says. “We see policies like this as sacrificing patients to the battle over high drug prices. It’s bad practice, bad for patient outcomes, and nobody – apart from the payer – benefits.”

In ACR’s 2020 Rheumatic Disease Patient Survey, nearly half of 1,109 online survey respondents who had rheumatic diseases reported out-of-pocket costs greater than $1,000 per year for treatment. An IQVIA report from 2016 found that one in four specialty brand prescriptions are abandoned during the deductible phase, three times the rate seen when there is no deductible.

In an Oct. 7 letter to UHC, the 12 groups acknowledged that the drugs targeted by the accumulator policy are expensive. “However, they are also vitally important for our patients.” In addition to the ACR, the organizations involved include the AIDS Institute, American Academy of Dermatology Association, American Academy of Neurology, American College of Gastroenterology, American Gastroenterological Association, American Kidney Fund, Arthritis Foundation, Association for Clinical Oncology, Cancer Support Community, Coalition of State Rheumatology Organizations, and National Multiple Sclerosis Society.

UHC did not reply to questions in time for publication.


 

First large-scale payer to try copay accumulator program

Under UHC’s proposed policy, providers will be required to use UHC’s portal to report payment information received from drug manufacturer copay assistance programs that are applied to patients’ cost share of these drugs through a complex, 14-step “coupon submission process” involving multiple technology interfaces. “My first oath as a physician is to do no harm to my patient. Many of us are concerned about making these reports, which could harm our patients and undermine the doctor-patient relationship,” Dr. Phillips said.

“If I don’t report, what happens? I don’t think we know the answer to that. Some of us may decide we need to part ways with UHC.” Others may decline to participate in the drug manufacturers’ coupon programs beyond simply informing patients that manufacturer assistance is available.

“We’ve watched these copay accumulator policies for several years,” he said. “Some of them are rather opaque, with names like ‘copay savings programs’ or ‘copay value programs.’ But we had not seen a large-scale payer try to do this until now. Let’s face it: If UHC’s policy goes through, you can count the days until we see it from others.”

The Department of Health & Human Services, in its May 2020 final federal “Notice of Benefit and Payment Parameters for 2021,” indicated that individual states have the responsibility to regulate copay accumulator programs. Five states have banned them or restricted their use for individual and small group health plans. Arizona, Illinois, Virginia, and West Virginia passed such laws in 2019, and Georgia did so earlier this year.

“In next year’s state legislative sessions, we’ll make it a priority to pursue similar laws in other states,” Dr. Phillips said. “I’d encourage rheumatologists to educate their patients on the issues and be active in advocating for them.”

Last month, the American College of Rheumatology joined with 11 other medical associations and disease societies asking health insurance giant UnitedHealthcare (UHC) to not proceed with its proposed copay accumulator medical benefit program.

Copay accumulators are policies adopted by insurance companies or their pharmacy benefit managers to exclude patient copayment assistance programs for high-cost drugs, which are promulgated by the drug manufacturers, from being applied to a patient’s annual deductibles or out-of-pocket maximums. The manufacturer’s copay assistance, such as in the form of coupons, is designed to minimize the patient’s out-of-pocket costs. But insurers believe manufacturers will have no pressure to lower the prices of expensive specialty drugs unless patients are unable to afford them. Copay accumulators thus are aimed at giving insurers more leverage in negotiating prices for high-cost drugs.

UHC issued its new copay accumulator protocol for commercial individual and fully insured group plans in early October, effective Jan. 1, 2021, “in order to align employer costs for specialty medications with actual member out of pocket and deductibles,” according to the company’s announcement. In other words, patients will need to pay a higher share of the costs of these medications, said rheumatologist Christopher Phillips, MD, who chairs the Insurance Subcommittee of ACR’s Rheumatologic Care Committee. The annual price of biologic therapies for rheumatologic conditions ranges from $22,000 to $44,000, according to a recent press release from ACR.

The copay accumulator will negate the benefits of manufacturers’ copayment assistance programs for the patient, shifting more of the cost to the patient. With patients being forced to pay a higher share of drug costs for expensive biologic treatments for rheumatoid arthritis, lupus, and other rheumatologic conditions, they’ll stop taking the treatments, Dr. Phillips said.

“In my solo rheumatology practice in Paducah, Kentucky, when I’ve seen this kind of program applied on the pharmacy benefit side, rather than the medical benefit side, almost uniformly patients stop taking the high-cost treatments.” That can lead to disease flares, complications, and permanent disability. The newer rheumatologic drugs can cost $500 to $1,000 per treatment, and in many cases, there’s no generic or lower-cost alternative, he says. “We see policies like this as sacrificing patients to the battle over high drug prices. It’s bad practice, bad for patient outcomes, and nobody – apart from the payer – benefits.”

In ACR’s 2020 Rheumatic Disease Patient Survey, nearly half of 1,109 online survey respondents who had rheumatic diseases reported out-of-pocket costs greater than $1,000 per year for treatment. An IQVIA report from 2016 found that one in four specialty brand prescriptions are abandoned during the deductible phase, three times the rate seen when there is no deductible.

In an Oct. 7 letter to UHC, the 12 groups acknowledged that the drugs targeted by the accumulator policy are expensive. “However, they are also vitally important for our patients.” In addition to the ACR, the organizations involved include the AIDS Institute, American Academy of Dermatology Association, American Academy of Neurology, American College of Gastroenterology, American Gastroenterological Association, American Kidney Fund, Arthritis Foundation, Association for Clinical Oncology, Cancer Support Community, Coalition of State Rheumatology Organizations, and National Multiple Sclerosis Society.

UHC did not reply to questions in time for publication.


 

First large-scale payer to try copay accumulator program

Under UHC’s proposed policy, providers will be required to use UHC’s portal to report payment information received from drug manufacturer copay assistance programs that are applied to patients’ cost share of these drugs through a complex, 14-step “coupon submission process” involving multiple technology interfaces. “My first oath as a physician is to do no harm to my patient. Many of us are concerned about making these reports, which could harm our patients and undermine the doctor-patient relationship,” Dr. Phillips said.

“If I don’t report, what happens? I don’t think we know the answer to that. Some of us may decide we need to part ways with UHC.” Others may decline to participate in the drug manufacturers’ coupon programs beyond simply informing patients that manufacturer assistance is available.

“We’ve watched these copay accumulator policies for several years,” he said. “Some of them are rather opaque, with names like ‘copay savings programs’ or ‘copay value programs.’ But we had not seen a large-scale payer try to do this until now. Let’s face it: If UHC’s policy goes through, you can count the days until we see it from others.”

The Department of Health & Human Services, in its May 2020 final federal “Notice of Benefit and Payment Parameters for 2021,” indicated that individual states have the responsibility to regulate copay accumulator programs. Five states have banned them or restricted their use for individual and small group health plans. Arizona, Illinois, Virginia, and West Virginia passed such laws in 2019, and Georgia did so earlier this year.

“In next year’s state legislative sessions, we’ll make it a priority to pursue similar laws in other states,” Dr. Phillips said. “I’d encourage rheumatologists to educate their patients on the issues and be active in advocating for them.”

A gel derived from birch bark is the first topical medication ever tested in the treatment of epidermolysis bullosa (EB) to heal wounds faster than placebo. The results come from the largest double-blind, randomized trial performed in this patient population.

Dr. Dedee Murrell

More than 41% of EB target wounds that were treated with Oleogel-S10 healed within 45 days, compared with about 29% of target wounds treated with placebo, in the EASE phase 3 trial, conducted at 58 sites in 28 countries.

A group of rare genetic disorders, EB “is described as the worst disease you’ve never heard of,” explained lead investigator Dedee Murrell, MD, director of dermatology, St. George Hospital at the University of New South Wales, Sydney. “It starts in children and is like having burns that heal with scars, and no treatment has been approved for it” by the Food and Drug Administration.

“This is the first large clinical trial with placebo of a topical treatment that’s worked for this terrible disease,” Dr. Murrell said in an interview. She noted that standard EB treatment currently consists of applying nonstick dressings to wounds to protect skin from trauma and infection.

Dr. Murrell, who has focused her work on EB patients since 1990, presented the findings at the virtual annual Congress of the European Academy of Dermatology and Venereology.

The trial enrolled 223 patients (average age, 12 years, but ages ranged to 81 years) with three types of EB, including dystrophic and junctional EB and Kindler syndrome. For each participant, a target wound was selected for use as the primary efficacy endpoint. Those wounds had a partial thickness of between 10 cm² and 50 cm² and lasted between 21 days and 9 months. Patients were stratified into groups depending on type of EB and size of target wound.

Participants were randomly assigned to receive either Oleogel-S10 (n = 109) or placebo (n = 114). All applied the blinded-study gel to all their wounds at least every 4 days at the time dressings were changed.

The primary endpoint was the percentage of patients whose target wounds completely closed within 45 days. Key secondary endpoints included time to wound healing and percentage of target wounds that healed within 90 days of treatment; incidence and severity of target wound infection; change in total body wound burden, as measured by the Epidermolysis Bullosa Disease Activity and Scarring Index skin activity subscore; change in itching, as measured by the Itch Man Scale and the Leuven Itch Scale; and adverse events.

Nearly 92% of patients who were treated with Oleogel-S10 completed the double-blind phase of the trial, compared with nearly 87% who received placebo. As noted, the primary endpoint was met, with 41.3% of Oleogel-S10 patients achieving target wound closure within 45 days, compared with 28.9% of the patients who received placebo (P = .013).

But the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of Oleogel-S10 patients achieving wound closure vs. 43.9% of control patients.

Target-wound infection occurred in eight participants, including three who used Oleogel-S10 and five who received placebo; all moderate or severe infections occurred in patients who received placebo. Total wound burden was reduced to a greater extent among Oleogel-S10 patients by day 60, but there was no apparent difference at day 90.

Both treatment groups reported qualitative improvements in itch, with no significant differences between groups. The prevalence of adverse events was also similar between groups (Oleogel-S10, 81.7%; placebo, 80.7%). The most frequently reported adverse events among Oleogel-S10 patients, compared with patients who received placebo, were wound complications, pyrexia, wound infection, pruritus, and anemia; only 4.5% of adverse events were deemed severe.

Dr. Murrell said that, on the basis of the trial results, she expects the FDA to fast-track approval of Oleogel-S10, which contains triterpene extract and sunflower oil.

The gel is “a treatment patients will be able to put under their dressings, added to normal treatment, which will accelerate their wound healing, with no significant increase in any side effects,” she added.

Jemima Mellerio, MD, of St. Thomas’ Hospital in London who sees about 400 EB patients each year, agreed with Dr. Murrell that the results are “very exciting.” Dr. Mellerio was not involved in the study.

“Practicing dermatologists seeing people with EB will have something to offer that appears to speed up wound healing in chronic wounds,” Dr. Mellerio said in an interview. “It’s a positive option rather than just supportive treatment, something that makes a difference to the natural history of wounds.”

She said the trial’s biggest strength was including “such a large cohort of patients.

“It’s extremely difficult to do that kind of study, especially with a placebo-controlled arm and especially in a rare disease,” Dr. Mellerio said. “If you think about the product itself, it’s easy to apply, so it’s not particularly onerous for people to add to their daily regimen of dressings.”

The study was funded by Amryt Pharma. Dr. Murrell is an advisory board member for Amryt Pharma. Dr. Mellerio is a consultant for Amryt Pharma.

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

A gel derived from birch bark is the first topical medication ever tested in the treatment of epidermolysis bullosa (EB) to heal wounds faster than placebo. The results come from the largest double-blind, randomized trial performed in this patient population.

Dr. Dedee Murrell

More than 41% of EB target wounds that were treated with Oleogel-S10 healed within 45 days, compared with about 29% of target wounds treated with placebo, in the EASE phase 3 trial, conducted at 58 sites in 28 countries.

A group of rare genetic disorders, EB “is described as the worst disease you’ve never heard of,” explained lead investigator Dedee Murrell, MD, director of dermatology, St. George Hospital at the University of New South Wales, Sydney. “It starts in children and is like having burns that heal with scars, and no treatment has been approved for it” by the Food and Drug Administration.

“This is the first large clinical trial with placebo of a topical treatment that’s worked for this terrible disease,” Dr. Murrell said in an interview. She noted that standard EB treatment currently consists of applying nonstick dressings to wounds to protect skin from trauma and infection.

Dr. Murrell, who has focused her work on EB patients since 1990, presented the findings at the virtual annual Congress of the European Academy of Dermatology and Venereology.

The trial enrolled 223 patients (average age, 12 years, but ages ranged to 81 years) with three types of EB, including dystrophic and junctional EB and Kindler syndrome. For each participant, a target wound was selected for use as the primary efficacy endpoint. Those wounds had a partial thickness of between 10 cm² and 50 cm² and lasted between 21 days and 9 months. Patients were stratified into groups depending on type of EB and size of target wound.

Participants were randomly assigned to receive either Oleogel-S10 (n = 109) or placebo (n = 114). All applied the blinded-study gel to all their wounds at least every 4 days at the time dressings were changed.

The primary endpoint was the percentage of patients whose target wounds completely closed within 45 days. Key secondary endpoints included time to wound healing and percentage of target wounds that healed within 90 days of treatment; incidence and severity of target wound infection; change in total body wound burden, as measured by the Epidermolysis Bullosa Disease Activity and Scarring Index skin activity subscore; change in itching, as measured by the Itch Man Scale and the Leuven Itch Scale; and adverse events.

Nearly 92% of patients who were treated with Oleogel-S10 completed the double-blind phase of the trial, compared with nearly 87% who received placebo. As noted, the primary endpoint was met, with 41.3% of Oleogel-S10 patients achieving target wound closure within 45 days, compared with 28.9% of the patients who received placebo (P = .013).

But the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of Oleogel-S10 patients achieving wound closure vs. 43.9% of control patients.

Target-wound infection occurred in eight participants, including three who used Oleogel-S10 and five who received placebo; all moderate or severe infections occurred in patients who received placebo. Total wound burden was reduced to a greater extent among Oleogel-S10 patients by day 60, but there was no apparent difference at day 90.

Both treatment groups reported qualitative improvements in itch, with no significant differences between groups. The prevalence of adverse events was also similar between groups (Oleogel-S10, 81.7%; placebo, 80.7%). The most frequently reported adverse events among Oleogel-S10 patients, compared with patients who received placebo, were wound complications, pyrexia, wound infection, pruritus, and anemia; only 4.5% of adverse events were deemed severe.

Dr. Murrell said that, on the basis of the trial results, she expects the FDA to fast-track approval of Oleogel-S10, which contains triterpene extract and sunflower oil.

The gel is “a treatment patients will be able to put under their dressings, added to normal treatment, which will accelerate their wound healing, with no significant increase in any side effects,” she added.

Jemima Mellerio, MD, of St. Thomas’ Hospital in London who sees about 400 EB patients each year, agreed with Dr. Murrell that the results are “very exciting.” Dr. Mellerio was not involved in the study.

“Practicing dermatologists seeing people with EB will have something to offer that appears to speed up wound healing in chronic wounds,” Dr. Mellerio said in an interview. “It’s a positive option rather than just supportive treatment, something that makes a difference to the natural history of wounds.”

She said the trial’s biggest strength was including “such a large cohort of patients.

“It’s extremely difficult to do that kind of study, especially with a placebo-controlled arm and especially in a rare disease,” Dr. Mellerio said. “If you think about the product itself, it’s easy to apply, so it’s not particularly onerous for people to add to their daily regimen of dressings.”

The study was funded by Amryt Pharma. Dr. Murrell is an advisory board member for Amryt Pharma. Dr. Mellerio is a consultant for Amryt Pharma.

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

A gel derived from birch bark is the first topical medication ever tested in the treatment of epidermolysis bullosa (EB) to heal wounds faster than placebo. The results come from the largest double-blind, randomized trial performed in this patient population.

Dr. Dedee Murrell

More than 41% of EB target wounds that were treated with Oleogel-S10 healed within 45 days, compared with about 29% of target wounds treated with placebo, in the EASE phase 3 trial, conducted at 58 sites in 28 countries.

A group of rare genetic disorders, EB “is described as the worst disease you’ve never heard of,” explained lead investigator Dedee Murrell, MD, director of dermatology, St. George Hospital at the University of New South Wales, Sydney. “It starts in children and is like having burns that heal with scars, and no treatment has been approved for it” by the Food and Drug Administration.

“This is the first large clinical trial with placebo of a topical treatment that’s worked for this terrible disease,” Dr. Murrell said in an interview. She noted that standard EB treatment currently consists of applying nonstick dressings to wounds to protect skin from trauma and infection.

Dr. Murrell, who has focused her work on EB patients since 1990, presented the findings at the virtual annual Congress of the European Academy of Dermatology and Venereology.

The trial enrolled 223 patients (average age, 12 years, but ages ranged to 81 years) with three types of EB, including dystrophic and junctional EB and Kindler syndrome. For each participant, a target wound was selected for use as the primary efficacy endpoint. Those wounds had a partial thickness of between 10 cm² and 50 cm² and lasted between 21 days and 9 months. Patients were stratified into groups depending on type of EB and size of target wound.

Participants were randomly assigned to receive either Oleogel-S10 (n = 109) or placebo (n = 114). All applied the blinded-study gel to all their wounds at least every 4 days at the time dressings were changed.

The primary endpoint was the percentage of patients whose target wounds completely closed within 45 days. Key secondary endpoints included time to wound healing and percentage of target wounds that healed within 90 days of treatment; incidence and severity of target wound infection; change in total body wound burden, as measured by the Epidermolysis Bullosa Disease Activity and Scarring Index skin activity subscore; change in itching, as measured by the Itch Man Scale and the Leuven Itch Scale; and adverse events.

Nearly 92% of patients who were treated with Oleogel-S10 completed the double-blind phase of the trial, compared with nearly 87% who received placebo. As noted, the primary endpoint was met, with 41.3% of Oleogel-S10 patients achieving target wound closure within 45 days, compared with 28.9% of the patients who received placebo (P = .013).

But the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of Oleogel-S10 patients achieving wound closure vs. 43.9% of control patients.

Target-wound infection occurred in eight participants, including three who used Oleogel-S10 and five who received placebo; all moderate or severe infections occurred in patients who received placebo. Total wound burden was reduced to a greater extent among Oleogel-S10 patients by day 60, but there was no apparent difference at day 90.

Both treatment groups reported qualitative improvements in itch, with no significant differences between groups. The prevalence of adverse events was also similar between groups (Oleogel-S10, 81.7%; placebo, 80.7%). The most frequently reported adverse events among Oleogel-S10 patients, compared with patients who received placebo, were wound complications, pyrexia, wound infection, pruritus, and anemia; only 4.5% of adverse events were deemed severe.

Dr. Murrell said that, on the basis of the trial results, she expects the FDA to fast-track approval of Oleogel-S10, which contains triterpene extract and sunflower oil.

The gel is “a treatment patients will be able to put under their dressings, added to normal treatment, which will accelerate their wound healing, with no significant increase in any side effects,” she added.

Jemima Mellerio, MD, of St. Thomas’ Hospital in London who sees about 400 EB patients each year, agreed with Dr. Murrell that the results are “very exciting.” Dr. Mellerio was not involved in the study.

“Practicing dermatologists seeing people with EB will have something to offer that appears to speed up wound healing in chronic wounds,” Dr. Mellerio said in an interview. “It’s a positive option rather than just supportive treatment, something that makes a difference to the natural history of wounds.”

She said the trial’s biggest strength was including “such a large cohort of patients.

“It’s extremely difficult to do that kind of study, especially with a placebo-controlled arm and especially in a rare disease,” Dr. Mellerio said. “If you think about the product itself, it’s easy to apply, so it’s not particularly onerous for people to add to their daily regimen of dressings.”

The study was funded by Amryt Pharma. Dr. Murrell is an advisory board member for Amryt Pharma. Dr. Mellerio is a consultant for Amryt Pharma.

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

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

[email protected]

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

[email protected]

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

[email protected]

Delgocitinib cream shows a dose-dependent response in easing chronic hand eczema, a common and difficult-to-treat disorder for which few other topical options are available, a new international phase 2b research suggests.

An investigational pan–Janus kinase inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild to severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.

“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of the department of dermatology, venereology, and allergology at Charité University Hospital in Berlin, during a presentation of the results at the virtual annual congress of the European Academy of Dermatology and Venereology.

“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Dr. Worm said in an interview. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”

Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Dr. Worm said.

Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors.

“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”

The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Dr. Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”

Dr. Worm and colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women; average age, 46 years) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.

The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment score of 0 (“clear”) or 1 (“almost clear”), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.

At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8-mg/g and 20-mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1-mg/g and 3-mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).

This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8-mg/g group and week 6 in the 20-mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).

“The strength of the trial is that there were different concentrations of the substance used,” Dr. Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”

Most adverse events reported were not considered treatment related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.

Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, said that phase 3 studies of delgocitinib should probe further into the effects of the 8-mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.

It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Dr. Bilgic said in an interview.

“Especially in the COVID era, many health care professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”

The study was funded by LEO Pharma. Dr. Worm received lecture honoraria from LEO Pharma. Dr. Bilgic disclosed no relevant financial relationships.

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

Delgocitinib cream shows a dose-dependent response in easing chronic hand eczema, a common and difficult-to-treat disorder for which few other topical options are available, a new international phase 2b research suggests.

An investigational pan–Janus kinase inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild to severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.

“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of the department of dermatology, venereology, and allergology at Charité University Hospital in Berlin, during a presentation of the results at the virtual annual congress of the European Academy of Dermatology and Venereology.

“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Dr. Worm said in an interview. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”

Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Dr. Worm said.

Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors.

“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”

The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Dr. Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”

Dr. Worm and colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women; average age, 46 years) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.

The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment score of 0 (“clear”) or 1 (“almost clear”), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.

At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8-mg/g and 20-mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1-mg/g and 3-mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).

This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8-mg/g group and week 6 in the 20-mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).

“The strength of the trial is that there were different concentrations of the substance used,” Dr. Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”

Most adverse events reported were not considered treatment related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.

Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, said that phase 3 studies of delgocitinib should probe further into the effects of the 8-mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.

It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Dr. Bilgic said in an interview.

“Especially in the COVID era, many health care professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”

The study was funded by LEO Pharma. Dr. Worm received lecture honoraria from LEO Pharma. Dr. Bilgic disclosed no relevant financial relationships.

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

Delgocitinib cream shows a dose-dependent response in easing chronic hand eczema, a common and difficult-to-treat disorder for which few other topical options are available, a new international phase 2b research suggests.

An investigational pan–Janus kinase inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild to severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.

“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of the department of dermatology, venereology, and allergology at Charité University Hospital in Berlin, during a presentation of the results at the virtual annual congress of the European Academy of Dermatology and Venereology.

“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Dr. Worm said in an interview. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”

Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Dr. Worm said.

Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors.

“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”

The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Dr. Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”

Dr. Worm and colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women; average age, 46 years) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.

The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment score of 0 (“clear”) or 1 (“almost clear”), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.

At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8-mg/g and 20-mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1-mg/g and 3-mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).

This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8-mg/g group and week 6 in the 20-mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).

“The strength of the trial is that there were different concentrations of the substance used,” Dr. Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”

Most adverse events reported were not considered treatment related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.

Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, said that phase 3 studies of delgocitinib should probe further into the effects of the 8-mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.

It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Dr. Bilgic said in an interview.

“Especially in the COVID era, many health care professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”

The study was funded by LEO Pharma. Dr. Worm received lecture honoraria from LEO Pharma. Dr. Bilgic disclosed no relevant financial relationships.

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

No clinically meaningful changes in laboratory values occurred in adolescents during 52 weeks on dupilumab for atopic dermatitis in a large, open-label safety study, Michael J. Cork, MBBS, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

These reassuring results from the ongoing LIBERTY AD PED-OLE study confirm that, as previously established in adults, no blood monitoring is required in adolescents on the monoclonal antibody, which inhibits signaling of interleukins-4 and -13, said Dr. Cork, professor of dermatology and head of Sheffield Dermatology Research at the University of Sheffield (England).

“The practical importance of this finding is that there are no other systemic drugs available that don’t require blood samples. Cyclosporine, methotrexate, and the others used for atopic dermatitis require a lot of blood monitoring, and they’re off-license anyway for use in children and adolescents,” he said in an interview.

Many pediatric patients are afraid of needles and have an intense dislike of blood draws. And in a pandemic, no one wants to come into the office for blood draws if they don’t need to.

“Blood draws are very different from the injection for dupilumab. Taking a blood sample is much more painful for children. The needle in the autoinjector is really, really tiny; you can hardly feel it, and with the autoinjector you can’t even see it,” noted Dr. Cork, who is both a pediatric and adult dermatologist.

This report from the ongoing LIBERTY AD PED-OLE study included 105 patients aged 12-17 years who completed 52 weeks on dupilumab (Dupixent) with assessments of hematologic and serum chemistry parameters at baseline and weeks 16 and 52.

“The results were anticipated, but we want to know the drug is safe in every age group. The immune system is different in different age groups, so we have to be really careful,” Dr. Cork said.

The clinical side-effect profile was the same as in adults, consisting mainly of mild conjunctivitis and injection-site reactions. It’s a much less problematic side effect picture than with the older drugs.

“We’re finding the conjunctivitis to be slightly less severe than in adults, maybe because we’ve learned from the first trials in adults and from clinical experience to use prophylactic therapy. There would be no child going on dupilumab now – and no adult – that I wouldn’t put on prophylactic eye drops with replacement tears. I start them 2 weeks before I start dupilumab,” the dermatologist explained.

He and others with extensive experience using the biologic agent also work closely with an ophthalmologist.

“If we see an eye problem before going on dupilumab we get an assessment and then ophthalmologic monitoring during treatment,” Dr. Cork said.

As a dermatologist specializing in atopic dermatitis, he confessed to feeling deprived over the years as he watched the multitude of targeted biologic agents being developed for psoriasis. When he became involved in the first pediatric clinical trials of dupilumab, he had a realization: “It’s a miraculous treatment.”

“The first child I put on dupilumab spent 70 days in the hospital for IV antibiotics in the prior year. Seventy days! He almost died from MRSA septicemia. His serum IgE was 155,000 kU/L. And his IgE just went down and down and down as the dupilumab took effect. It was just incredible,” he recalled.

Dr. Cork reported receiving research funding from and serving as a consultant to Sanofi and Regeneron, which fund the LIBERTY AD PED-OLE study, as well as numerous other pharmaceutical companies.

[email protected]

SOURCE: Cork MJ. EADV 2020, Abstract 1772.

No clinically meaningful changes in laboratory values occurred in adolescents during 52 weeks on dupilumab for atopic dermatitis in a large, open-label safety study, Michael J. Cork, MBBS, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

These reassuring results from the ongoing LIBERTY AD PED-OLE study confirm that, as previously established in adults, no blood monitoring is required in adolescents on the monoclonal antibody, which inhibits signaling of interleukins-4 and -13, said Dr. Cork, professor of dermatology and head of Sheffield Dermatology Research at the University of Sheffield (England).

“The practical importance of this finding is that there are no other systemic drugs available that don’t require blood samples. Cyclosporine, methotrexate, and the others used for atopic dermatitis require a lot of blood monitoring, and they’re off-license anyway for use in children and adolescents,” he said in an interview.

Many pediatric patients are afraid of needles and have an intense dislike of blood draws. And in a pandemic, no one wants to come into the office for blood draws if they don’t need to.

“Blood draws are very different from the injection for dupilumab. Taking a blood sample is much more painful for children. The needle in the autoinjector is really, really tiny; you can hardly feel it, and with the autoinjector you can’t even see it,” noted Dr. Cork, who is both a pediatric and adult dermatologist.

This report from the ongoing LIBERTY AD PED-OLE study included 105 patients aged 12-17 years who completed 52 weeks on dupilumab (Dupixent) with assessments of hematologic and serum chemistry parameters at baseline and weeks 16 and 52.

“The results were anticipated, but we want to know the drug is safe in every age group. The immune system is different in different age groups, so we have to be really careful,” Dr. Cork said.

The clinical side-effect profile was the same as in adults, consisting mainly of mild conjunctivitis and injection-site reactions. It’s a much less problematic side effect picture than with the older drugs.

“We’re finding the conjunctivitis to be slightly less severe than in adults, maybe because we’ve learned from the first trials in adults and from clinical experience to use prophylactic therapy. There would be no child going on dupilumab now – and no adult – that I wouldn’t put on prophylactic eye drops with replacement tears. I start them 2 weeks before I start dupilumab,” the dermatologist explained.

He and others with extensive experience using the biologic agent also work closely with an ophthalmologist.

“If we see an eye problem before going on dupilumab we get an assessment and then ophthalmologic monitoring during treatment,” Dr. Cork said.

As a dermatologist specializing in atopic dermatitis, he confessed to feeling deprived over the years as he watched the multitude of targeted biologic agents being developed for psoriasis. When he became involved in the first pediatric clinical trials of dupilumab, he had a realization: “It’s a miraculous treatment.”

“The first child I put on dupilumab spent 70 days in the hospital for IV antibiotics in the prior year. Seventy days! He almost died from MRSA septicemia. His serum IgE was 155,000 kU/L. And his IgE just went down and down and down as the dupilumab took effect. It was just incredible,” he recalled.

Dr. Cork reported receiving research funding from and serving as a consultant to Sanofi and Regeneron, which fund the LIBERTY AD PED-OLE study, as well as numerous other pharmaceutical companies.

[email protected]

SOURCE: Cork MJ. EADV 2020, Abstract 1772.

No clinically meaningful changes in laboratory values occurred in adolescents during 52 weeks on dupilumab for atopic dermatitis in a large, open-label safety study, Michael J. Cork, MBBS, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

These reassuring results from the ongoing LIBERTY AD PED-OLE study confirm that, as previously established in adults, no blood monitoring is required in adolescents on the monoclonal antibody, which inhibits signaling of interleukins-4 and -13, said Dr. Cork, professor of dermatology and head of Sheffield Dermatology Research at the University of Sheffield (England).

“The practical importance of this finding is that there are no other systemic drugs available that don’t require blood samples. Cyclosporine, methotrexate, and the others used for atopic dermatitis require a lot of blood monitoring, and they’re off-license anyway for use in children and adolescents,” he said in an interview.

Many pediatric patients are afraid of needles and have an intense dislike of blood draws. And in a pandemic, no one wants to come into the office for blood draws if they don’t need to.

“Blood draws are very different from the injection for dupilumab. Taking a blood sample is much more painful for children. The needle in the autoinjector is really, really tiny; you can hardly feel it, and with the autoinjector you can’t even see it,” noted Dr. Cork, who is both a pediatric and adult dermatologist.

This report from the ongoing LIBERTY AD PED-OLE study included 105 patients aged 12-17 years who completed 52 weeks on dupilumab (Dupixent) with assessments of hematologic and serum chemistry parameters at baseline and weeks 16 and 52.

“The results were anticipated, but we want to know the drug is safe in every age group. The immune system is different in different age groups, so we have to be really careful,” Dr. Cork said.

The clinical side-effect profile was the same as in adults, consisting mainly of mild conjunctivitis and injection-site reactions. It’s a much less problematic side effect picture than with the older drugs.

“We’re finding the conjunctivitis to be slightly less severe than in adults, maybe because we’ve learned from the first trials in adults and from clinical experience to use prophylactic therapy. There would be no child going on dupilumab now – and no adult – that I wouldn’t put on prophylactic eye drops with replacement tears. I start them 2 weeks before I start dupilumab,” the dermatologist explained.

He and others with extensive experience using the biologic agent also work closely with an ophthalmologist.

“If we see an eye problem before going on dupilumab we get an assessment and then ophthalmologic monitoring during treatment,” Dr. Cork said.

As a dermatologist specializing in atopic dermatitis, he confessed to feeling deprived over the years as he watched the multitude of targeted biologic agents being developed for psoriasis. When he became involved in the first pediatric clinical trials of dupilumab, he had a realization: “It’s a miraculous treatment.”

“The first child I put on dupilumab spent 70 days in the hospital for IV antibiotics in the prior year. Seventy days! He almost died from MRSA septicemia. His serum IgE was 155,000 kU/L. And his IgE just went down and down and down as the dupilumab took effect. It was just incredible,” he recalled.

Dr. Cork reported receiving research funding from and serving as a consultant to Sanofi and Regeneron, which fund the LIBERTY AD PED-OLE study, as well as numerous other pharmaceutical companies.

[email protected]

SOURCE: Cork MJ. EADV 2020, Abstract 1772.

The Food and Drug Administration has approved 0.5% lotion formulation of ivermectin (Sklice) as an over-the-counter treatment for head lice infestation in patients aged 6 months and older.

Ivermectin was approved as a prescription treatment for head lice in February 2012, according to an FDA press release, and is now approved as an over-the-counter treatment through an “Rx-to-OTC” switch process. The approval was granted to Arbor Pharmaceuticals.

The expanded approval for ivermectin increases access to effective care for head lice, which is estimated to affect between 6 million and 12 million children each year in the United States, according to the Centers for Disease Control and Prevention.

“The Rx-to-OTC switch process aims to promote public health by increasing consumer access to drugs that would otherwise only be available by prescription,” Theresa Michele, MD, acting director of the Office of Nonprescription Drugs in the FDA’s Center for Drug Evaluation and Research, said in the press release.

The FDA also noted in the press release that “Sklice, and its active ingredient ivermectin, have not been shown to be safe or effective for the treatment or prevention of COVID-19 and they are not FDA-approved for this use.”

The drug is approved only for treating head lice, and should be used on the scalp and dry hair, according to the labeling. In the wake of the approval, ivermectin will no longer be available as a prescription drug, according to the FDA, and patients currently using prescription versions should contact their health care providers.

An Rx-to-OTC switch is contingent on the manufacturer’s data showing that the drug is safe and effective when used as directed. In addition, “the manufacturer must show that consumers can understand how to use the drug safely and effectively without the supervision of a health care professional,” according to the FDA.

The Food and Drug Administration has approved 0.5% lotion formulation of ivermectin (Sklice) as an over-the-counter treatment for head lice infestation in patients aged 6 months and older.

Ivermectin was approved as a prescription treatment for head lice in February 2012, according to an FDA press release, and is now approved as an over-the-counter treatment through an “Rx-to-OTC” switch process. The approval was granted to Arbor Pharmaceuticals.

The expanded approval for ivermectin increases access to effective care for head lice, which is estimated to affect between 6 million and 12 million children each year in the United States, according to the Centers for Disease Control and Prevention.

“The Rx-to-OTC switch process aims to promote public health by increasing consumer access to drugs that would otherwise only be available by prescription,” Theresa Michele, MD, acting director of the Office of Nonprescription Drugs in the FDA’s Center for Drug Evaluation and Research, said in the press release.

The FDA also noted in the press release that “Sklice, and its active ingredient ivermectin, have not been shown to be safe or effective for the treatment or prevention of COVID-19 and they are not FDA-approved for this use.”

The drug is approved only for treating head lice, and should be used on the scalp and dry hair, according to the labeling. In the wake of the approval, ivermectin will no longer be available as a prescription drug, according to the FDA, and patients currently using prescription versions should contact their health care providers.

An Rx-to-OTC switch is contingent on the manufacturer’s data showing that the drug is safe and effective when used as directed. In addition, “the manufacturer must show that consumers can understand how to use the drug safely and effectively without the supervision of a health care professional,” according to the FDA.

The Food and Drug Administration has approved 0.5% lotion formulation of ivermectin (Sklice) as an over-the-counter treatment for head lice infestation in patients aged 6 months and older.

Ivermectin was approved as a prescription treatment for head lice in February 2012, according to an FDA press release, and is now approved as an over-the-counter treatment through an “Rx-to-OTC” switch process. The approval was granted to Arbor Pharmaceuticals.

The expanded approval for ivermectin increases access to effective care for head lice, which is estimated to affect between 6 million and 12 million children each year in the United States, according to the Centers for Disease Control and Prevention.

“The Rx-to-OTC switch process aims to promote public health by increasing consumer access to drugs that would otherwise only be available by prescription,” Theresa Michele, MD, acting director of the Office of Nonprescription Drugs in the FDA’s Center for Drug Evaluation and Research, said in the press release.

The FDA also noted in the press release that “Sklice, and its active ingredient ivermectin, have not been shown to be safe or effective for the treatment or prevention of COVID-19 and they are not FDA-approved for this use.”

The drug is approved only for treating head lice, and should be used on the scalp and dry hair, according to the labeling. In the wake of the approval, ivermectin will no longer be available as a prescription drug, according to the FDA, and patients currently using prescription versions should contact their health care providers.

An Rx-to-OTC switch is contingent on the manufacturer’s data showing that the drug is safe and effective when used as directed. In addition, “the manufacturer must show that consumers can understand how to use the drug safely and effectively without the supervision of a health care professional,” according to the FDA.

The patient was given a diagnosis of prurigo pigmentosa based on the characteristic pruritic rash that had developed after the patient started a strict ketogenic diet.

Prurigo pigmentosa is a benign, pruritic rash that most commonly presents with erythematous or hyperpigmented, symmetrically distributed urticarial papules and plaques on the chest and back. Females represent approximately 70% of cases with a predominant age range of 11 to 30. It more commonly is seen in people of Asian descent.

While the pathophysiology remains unknown, the rash most commonly occurs in association with diabetes, ketosis, and more recently with ketogenic diets. Despite occurring in only a fraction of patients on the ketogenic diet, the characteristic presentation has led to the alternative name of the “keto rash” in online nutritional forums and blogs.

The diagnosis is made clinically, so the appearance of a symmetric pruritic, hyperpigmented rash on the chest and back should prompt the physician to ask about any recent changes in diet. Laboratory analysis is unnecessary, as a complete blood count, basic metabolic panel, and liver function panel are almost always normal.

Other conditions can mimic prurigo pigmentosa such as urticaria, irritant contact dermatitis, confluent and reticulated papillomatosis, and pityriasis rosea.

Primary treatment includes resumption of a normal diet. This often leads to rapid resolution of pruritis. Residual hyperpigmentation may take months to fade. If additional treatment is required, minocycline 100 to 200 mg/d has been reported most effective, likely due to its anti-inflammatory properties. Topical corticosteroids and oral antihistamines provide symptomatic relief in some patients.

This patient had resolution of the pruritis and urticarial lesions within 2 days of resuming a normal diet; however, residual asymptomatic hyperpigmentation persisted. A retrial of the ketogenic diet initiated a flare of the rash in the same distribution. It rapidly resolved with carbohydrate intake.

‌

This case was adapted from: Croom D, Barlow T, Landers JT. Pruritic rash on chest and back. J Fam Pract. 2019;68:113-114,116

The patient was given a diagnosis of prurigo pigmentosa based on the characteristic pruritic rash that had developed after the patient started a strict ketogenic diet.

Prurigo pigmentosa is a benign, pruritic rash that most commonly presents with erythematous or hyperpigmented, symmetrically distributed urticarial papules and plaques on the chest and back. Females represent approximately 70% of cases with a predominant age range of 11 to 30. It more commonly is seen in people of Asian descent.

While the pathophysiology remains unknown, the rash most commonly occurs in association with diabetes, ketosis, and more recently with ketogenic diets. Despite occurring in only a fraction of patients on the ketogenic diet, the characteristic presentation has led to the alternative name of the “keto rash” in online nutritional forums and blogs.

The diagnosis is made clinically, so the appearance of a symmetric pruritic, hyperpigmented rash on the chest and back should prompt the physician to ask about any recent changes in diet. Laboratory analysis is unnecessary, as a complete blood count, basic metabolic panel, and liver function panel are almost always normal.

Other conditions can mimic prurigo pigmentosa such as urticaria, irritant contact dermatitis, confluent and reticulated papillomatosis, and pityriasis rosea.

Primary treatment includes resumption of a normal diet. This often leads to rapid resolution of pruritis. Residual hyperpigmentation may take months to fade. If additional treatment is required, minocycline 100 to 200 mg/d has been reported most effective, likely due to its anti-inflammatory properties. Topical corticosteroids and oral antihistamines provide symptomatic relief in some patients.

This patient had resolution of the pruritis and urticarial lesions within 2 days of resuming a normal diet; however, residual asymptomatic hyperpigmentation persisted. A retrial of the ketogenic diet initiated a flare of the rash in the same distribution. It rapidly resolved with carbohydrate intake.

‌

This case was adapted from: Croom D, Barlow T, Landers JT. Pruritic rash on chest and back. J Fam Pract. 2019;68:113-114,116

The patient was given a diagnosis of prurigo pigmentosa based on the characteristic pruritic rash that had developed after the patient started a strict ketogenic diet.

Prurigo pigmentosa is a benign, pruritic rash that most commonly presents with erythematous or hyperpigmented, symmetrically distributed urticarial papules and plaques on the chest and back. Females represent approximately 70% of cases with a predominant age range of 11 to 30. It more commonly is seen in people of Asian descent.

While the pathophysiology remains unknown, the rash most commonly occurs in association with diabetes, ketosis, and more recently with ketogenic diets. Despite occurring in only a fraction of patients on the ketogenic diet, the characteristic presentation has led to the alternative name of the “keto rash” in online nutritional forums and blogs.

The diagnosis is made clinically, so the appearance of a symmetric pruritic, hyperpigmented rash on the chest and back should prompt the physician to ask about any recent changes in diet. Laboratory analysis is unnecessary, as a complete blood count, basic metabolic panel, and liver function panel are almost always normal.

Other conditions can mimic prurigo pigmentosa such as urticaria, irritant contact dermatitis, confluent and reticulated papillomatosis, and pityriasis rosea.

Primary treatment includes resumption of a normal diet. This often leads to rapid resolution of pruritis. Residual hyperpigmentation may take months to fade. If additional treatment is required, minocycline 100 to 200 mg/d has been reported most effective, likely due to its anti-inflammatory properties. Topical corticosteroids and oral antihistamines provide symptomatic relief in some patients.

This patient had resolution of the pruritis and urticarial lesions within 2 days of resuming a normal diet; however, residual asymptomatic hyperpigmentation persisted. A retrial of the ketogenic diet initiated a flare of the rash in the same distribution. It rapidly resolved with carbohydrate intake.

‌

This case was adapted from: Croom D, Barlow T, Landers JT. Pruritic rash on chest and back. J Fam Pract. 2019;68:113-114,116

When assessing inflammatory dermatoses in children with skin of color, it may be necessary to train the eye to recognize subtle changes and colors other than red, a doctor suggested at the virtual American Academy of Pediatrics annual meeting.

First, doctors should see whether they can detect any erythema, said Latanya T. Benjamin, MD, associate professor of pediatric dermatology at Florida Atlantic University, Boca Raton. “If the answer is no because of the background competing chromophore, then shift your focus off of the erythema and perhaps onto other colors that the skin can demonstrate,” such as red-brown, violaceous, or grayish hues.

Comparing involved areas with normal skin also may help. “Sometimes you can pick up subtleties in colors that way,” Dr. Benjamin said.

Finally, look for other changes that could relate to the patient’s condition. For example, when diagnosing acne, Dr. Benjamin looks for pigmentary sequelae like hyperpigmentation. “If a patient has atopic dermatitis, is there hypopigmentation on other areas of the face?”

Consider cutaneous T-cell lymphoma in the differential diagnosis of generalized hypopigmented patches and plaques in patients with darker skin types, Dr. Benjamin noted. Other diagnoses that may result in hypopigmentation include pityriasis alba, vitiligo, tinea versicolor, ash-leaf macules, Hansen’s disease, postinflammatory hypopigmentation secondary to atopic dermatitis, and tinea corporis.

Be sensitive to the fact that changes in skin color can be “very annoying or devastating to the family,” even with medically benign conditions such as pityriasis alba, Dr. Benjamin added.

Detecting redness in brown skin tones can take practice, Candrice R. Heath, MD, a member of the board of directors for the Skin of Color Society, commented in an interview.

Furthermore, presentations vary. For instance, depictions of atopic dermatitis in educational materials may focus on red patches and plaques but “miss that there are several presentations in those with darker skin tones, including follicular prominence, hyperpigmented plaques, and coin-shaped lesions,” said Dr. Heath, assistant professor of dermatology at Temple University, Philadelphia.

“The skin of color population is growing,” noted Dr. Heath. “By 2023, there will be more children with skin of color than without in the United States.”

While Dr. Heath has lectured about skin of color as it relates to pediatric patients for years, “now with the nation’s renewed interest in disparities in health care, it is the perfect time to highlight conditions that present more commonly in skin of color and present differently in those with skin of color.”

Dr. Benjamin had no conflicts of interest. Dr. Heath serves as associate editor of Cutis, which is owned by the same company as this publication.

[email protected]

When assessing inflammatory dermatoses in children with skin of color, it may be necessary to train the eye to recognize subtle changes and colors other than red, a doctor suggested at the virtual American Academy of Pediatrics annual meeting.

First, doctors should see whether they can detect any erythema, said Latanya T. Benjamin, MD, associate professor of pediatric dermatology at Florida Atlantic University, Boca Raton. “If the answer is no because of the background competing chromophore, then shift your focus off of the erythema and perhaps onto other colors that the skin can demonstrate,” such as red-brown, violaceous, or grayish hues.

Comparing involved areas with normal skin also may help. “Sometimes you can pick up subtleties in colors that way,” Dr. Benjamin said.

Finally, look for other changes that could relate to the patient’s condition. For example, when diagnosing acne, Dr. Benjamin looks for pigmentary sequelae like hyperpigmentation. “If a patient has atopic dermatitis, is there hypopigmentation on other areas of the face?”

Consider cutaneous T-cell lymphoma in the differential diagnosis of generalized hypopigmented patches and plaques in patients with darker skin types, Dr. Benjamin noted. Other diagnoses that may result in hypopigmentation include pityriasis alba, vitiligo, tinea versicolor, ash-leaf macules, Hansen’s disease, postinflammatory hypopigmentation secondary to atopic dermatitis, and tinea corporis.

Be sensitive to the fact that changes in skin color can be “very annoying or devastating to the family,” even with medically benign conditions such as pityriasis alba, Dr. Benjamin added.

Detecting redness in brown skin tones can take practice, Candrice R. Heath, MD, a member of the board of directors for the Skin of Color Society, commented in an interview.

Furthermore, presentations vary. For instance, depictions of atopic dermatitis in educational materials may focus on red patches and plaques but “miss that there are several presentations in those with darker skin tones, including follicular prominence, hyperpigmented plaques, and coin-shaped lesions,” said Dr. Heath, assistant professor of dermatology at Temple University, Philadelphia.

“The skin of color population is growing,” noted Dr. Heath. “By 2023, there will be more children with skin of color than without in the United States.”

While Dr. Heath has lectured about skin of color as it relates to pediatric patients for years, “now with the nation’s renewed interest in disparities in health care, it is the perfect time to highlight conditions that present more commonly in skin of color and present differently in those with skin of color.”

Dr. Benjamin had no conflicts of interest. Dr. Heath serves as associate editor of Cutis, which is owned by the same company as this publication.

[email protected]

When assessing inflammatory dermatoses in children with skin of color, it may be necessary to train the eye to recognize subtle changes and colors other than red, a doctor suggested at the virtual American Academy of Pediatrics annual meeting.

First, doctors should see whether they can detect any erythema, said Latanya T. Benjamin, MD, associate professor of pediatric dermatology at Florida Atlantic University, Boca Raton. “If the answer is no because of the background competing chromophore, then shift your focus off of the erythema and perhaps onto other colors that the skin can demonstrate,” such as red-brown, violaceous, or grayish hues.

Comparing involved areas with normal skin also may help. “Sometimes you can pick up subtleties in colors that way,” Dr. Benjamin said.

Finally, look for other changes that could relate to the patient’s condition. For example, when diagnosing acne, Dr. Benjamin looks for pigmentary sequelae like hyperpigmentation. “If a patient has atopic dermatitis, is there hypopigmentation on other areas of the face?”

Consider cutaneous T-cell lymphoma in the differential diagnosis of generalized hypopigmented patches and plaques in patients with darker skin types, Dr. Benjamin noted. Other diagnoses that may result in hypopigmentation include pityriasis alba, vitiligo, tinea versicolor, ash-leaf macules, Hansen’s disease, postinflammatory hypopigmentation secondary to atopic dermatitis, and tinea corporis.

Be sensitive to the fact that changes in skin color can be “very annoying or devastating to the family,” even with medically benign conditions such as pityriasis alba, Dr. Benjamin added.

Detecting redness in brown skin tones can take practice, Candrice R. Heath, MD, a member of the board of directors for the Skin of Color Society, commented in an interview.

Furthermore, presentations vary. For instance, depictions of atopic dermatitis in educational materials may focus on red patches and plaques but “miss that there are several presentations in those with darker skin tones, including follicular prominence, hyperpigmented plaques, and coin-shaped lesions,” said Dr. Heath, assistant professor of dermatology at Temple University, Philadelphia.

“The skin of color population is growing,” noted Dr. Heath. “By 2023, there will be more children with skin of color than without in the United States.”

While Dr. Heath has lectured about skin of color as it relates to pediatric patients for years, “now with the nation’s renewed interest in disparities in health care, it is the perfect time to highlight conditions that present more commonly in skin of color and present differently in those with skin of color.”

Dr. Benjamin had no conflicts of interest. Dr. Heath serves as associate editor of Cutis, which is owned by the same company as this publication.

[email protected]