User login
Tips, contraindications for superficial chemical peels reviewed
CHICAGO – Heather Woolery-Lloyd, MD, says she’s generally “risk averse,” but when it comes to superficial chemical peels, she’s in her comfort zone.
Superficial peeling is “one of the most common cosmetic procedures that I do,” Dr. Woolery-Lloyd, director of the skin of color division in the dermatology department at the University of Miami, said at the Pigmentary Disorders Exchange Symposium.
In her practice, .
Contraindications are an active bacterial infection, open wounds, and active herpes simplex virus. “If someone looks like they even have a remnant of a cold sore, I tell them to come back,” she said.
Setting expectations for patients is critical, Dr. Woolery-Lloyd said, as a series of superficial peels is needed before the desired results are evident.
The peel she uses most is salicylic acid, a beta-hydroxy acid, at a strength of 20%-30%. “It’s very effective on our acne patients,” she said at the meeting, provided by MedscapeLIVE! “If you’re just starting with peels, I think this is a very safe one. You don’t have to time it, and you don’t have to neutralize it,” and at lower concentrations, is “very safe.”
Dr. Woolery-Lloyd provided these other tips during her presentation:
- Even superficial peels can be uncomfortable, she noted, so she keeps a fan nearby to use when needed to help with discomfort.
- Find the peel you’re comfortable with, master that peel, and don’t jump from peel to peel. Get familiar with the side effects and how to predict results.
- Stop retinoids up to 7 days before a peel. Consider placing the patient on hydroquinone before the chemical peel to decrease the risk of hyperpigmentation.
- Before the procedure, prep the skin with acetone or alcohol. Applying petrolatum helps protect around the eyes, alar crease, and other sensitive areas, “or anywhere you’re concerned about the depth of the peel.”
- Application with rough gauze helps avoid the waste that comes with makeup sponges soaking up the product. It also helps add exfoliation.
- Have everything ready before starting the procedure, including (depending on the peel), a neutralizer or soapless cleanser. Although peels are generally safe, you want to be able to remove one quickly, if needed, without having to leave the room.
- Start with the lowest concentration (salicylic acid or glycolic acid) then titrate up. Ask patients about any reactions they experienced with the previous peel before making the decision on the next concentration.
- For a peel to treat hyperpigmentation, she recommends one peel about every 4 weeks for a series of 5-6 peels.
- After a peel, the patient should use a mineral sunscreen; chemical sunscreens will sting.
Know your comfort zone
Conference chair Pearl Grimes, MD, director of The Vitiligo & Pigmentation Institute of Southern California in Los Angeles, said superficial peels are best for dermatologists new to peeling until they gain comfort with experience.
Superficial and medium-depth peels work well for mild to moderate photoaging, she said at the meeting.
“We know that in darker skin we have more intrinsic aging rather than photoaging. We have more textural changes, hyperpigmentation,” Dr. Grimes said.
For Fitzpatrick skin types I-III, she said, “you can do superficial, medium, and deep peels.” For darker skin types, “I typically stay in the superficial, medium range.”
She said that she uses retinoids to exfoliate before a superficial peel but added, “you’ve got to stop them early because retinoids can make a superficial peel a medium-depth peel.”
Taking photos is important before any procedure, she said, as is spending time with patients clarifying their outcome expectations.
“I love peeling,” Dr. Grimes said. “And it’s cost effective. If you don’t want to spend a ton of money, it’s amazing what you can achieve with chemical peeling.”
When asked by a member of the audience whether they avoid superficial peels in women who are pregnant or breastfeeding, both Dr. Woolery-Lloyd and Dr. Grimes said they do avoid them in those patients.
Dr. Grimes said she tells her patients, especially in the first trimester, “I am the most conservative woman on the planet. I do nothing during the first trimester.”
Dr. Woolery-Lloyd has been a speaker for Ortho Dermatologics, Loreal and EPI, and has done research for Pfizer, Galderma, Allergan, Arcutis, Vyne, Merz, and Eirion. She has been on advisory boards for Loreal, Allergan, Ortho Dermatologics, Pfize,r and Merz. Dr. Grimes reports grant/research Support from Clinuvel Pharmaceuticals, Incyte, Johnson & Johnson, LASEROPTEK, L’Oréal USA, Pfizer, Procter & Gamble, skinbetter science, and Versicolor Technologies, and is on the speakers bureau/receives honoraria for non-CME for Incyte and Procter & Gamble; and is a consultant or is on the advisory board for L’Oréal USA and Procter & Gamble. She has stock options in Versicolor Technologies.
CHICAGO – Heather Woolery-Lloyd, MD, says she’s generally “risk averse,” but when it comes to superficial chemical peels, she’s in her comfort zone.
Superficial peeling is “one of the most common cosmetic procedures that I do,” Dr. Woolery-Lloyd, director of the skin of color division in the dermatology department at the University of Miami, said at the Pigmentary Disorders Exchange Symposium.
In her practice, .
Contraindications are an active bacterial infection, open wounds, and active herpes simplex virus. “If someone looks like they even have a remnant of a cold sore, I tell them to come back,” she said.
Setting expectations for patients is critical, Dr. Woolery-Lloyd said, as a series of superficial peels is needed before the desired results are evident.
The peel she uses most is salicylic acid, a beta-hydroxy acid, at a strength of 20%-30%. “It’s very effective on our acne patients,” she said at the meeting, provided by MedscapeLIVE! “If you’re just starting with peels, I think this is a very safe one. You don’t have to time it, and you don’t have to neutralize it,” and at lower concentrations, is “very safe.”
Dr. Woolery-Lloyd provided these other tips during her presentation:
- Even superficial peels can be uncomfortable, she noted, so she keeps a fan nearby to use when needed to help with discomfort.
- Find the peel you’re comfortable with, master that peel, and don’t jump from peel to peel. Get familiar with the side effects and how to predict results.
- Stop retinoids up to 7 days before a peel. Consider placing the patient on hydroquinone before the chemical peel to decrease the risk of hyperpigmentation.
- Before the procedure, prep the skin with acetone or alcohol. Applying petrolatum helps protect around the eyes, alar crease, and other sensitive areas, “or anywhere you’re concerned about the depth of the peel.”
- Application with rough gauze helps avoid the waste that comes with makeup sponges soaking up the product. It also helps add exfoliation.
- Have everything ready before starting the procedure, including (depending on the peel), a neutralizer or soapless cleanser. Although peels are generally safe, you want to be able to remove one quickly, if needed, without having to leave the room.
- Start with the lowest concentration (salicylic acid or glycolic acid) then titrate up. Ask patients about any reactions they experienced with the previous peel before making the decision on the next concentration.
- For a peel to treat hyperpigmentation, she recommends one peel about every 4 weeks for a series of 5-6 peels.
- After a peel, the patient should use a mineral sunscreen; chemical sunscreens will sting.
Know your comfort zone
Conference chair Pearl Grimes, MD, director of The Vitiligo & Pigmentation Institute of Southern California in Los Angeles, said superficial peels are best for dermatologists new to peeling until they gain comfort with experience.
Superficial and medium-depth peels work well for mild to moderate photoaging, she said at the meeting.
“We know that in darker skin we have more intrinsic aging rather than photoaging. We have more textural changes, hyperpigmentation,” Dr. Grimes said.
For Fitzpatrick skin types I-III, she said, “you can do superficial, medium, and deep peels.” For darker skin types, “I typically stay in the superficial, medium range.”
She said that she uses retinoids to exfoliate before a superficial peel but added, “you’ve got to stop them early because retinoids can make a superficial peel a medium-depth peel.”
Taking photos is important before any procedure, she said, as is spending time with patients clarifying their outcome expectations.
“I love peeling,” Dr. Grimes said. “And it’s cost effective. If you don’t want to spend a ton of money, it’s amazing what you can achieve with chemical peeling.”
When asked by a member of the audience whether they avoid superficial peels in women who are pregnant or breastfeeding, both Dr. Woolery-Lloyd and Dr. Grimes said they do avoid them in those patients.
Dr. Grimes said she tells her patients, especially in the first trimester, “I am the most conservative woman on the planet. I do nothing during the first trimester.”
Dr. Woolery-Lloyd has been a speaker for Ortho Dermatologics, Loreal and EPI, and has done research for Pfizer, Galderma, Allergan, Arcutis, Vyne, Merz, and Eirion. She has been on advisory boards for Loreal, Allergan, Ortho Dermatologics, Pfize,r and Merz. Dr. Grimes reports grant/research Support from Clinuvel Pharmaceuticals, Incyte, Johnson & Johnson, LASEROPTEK, L’Oréal USA, Pfizer, Procter & Gamble, skinbetter science, and Versicolor Technologies, and is on the speakers bureau/receives honoraria for non-CME for Incyte and Procter & Gamble; and is a consultant or is on the advisory board for L’Oréal USA and Procter & Gamble. She has stock options in Versicolor Technologies.
CHICAGO – Heather Woolery-Lloyd, MD, says she’s generally “risk averse,” but when it comes to superficial chemical peels, she’s in her comfort zone.
Superficial peeling is “one of the most common cosmetic procedures that I do,” Dr. Woolery-Lloyd, director of the skin of color division in the dermatology department at the University of Miami, said at the Pigmentary Disorders Exchange Symposium.
In her practice, .
Contraindications are an active bacterial infection, open wounds, and active herpes simplex virus. “If someone looks like they even have a remnant of a cold sore, I tell them to come back,” she said.
Setting expectations for patients is critical, Dr. Woolery-Lloyd said, as a series of superficial peels is needed before the desired results are evident.
The peel she uses most is salicylic acid, a beta-hydroxy acid, at a strength of 20%-30%. “It’s very effective on our acne patients,” she said at the meeting, provided by MedscapeLIVE! “If you’re just starting with peels, I think this is a very safe one. You don’t have to time it, and you don’t have to neutralize it,” and at lower concentrations, is “very safe.”
Dr. Woolery-Lloyd provided these other tips during her presentation:
- Even superficial peels can be uncomfortable, she noted, so she keeps a fan nearby to use when needed to help with discomfort.
- Find the peel you’re comfortable with, master that peel, and don’t jump from peel to peel. Get familiar with the side effects and how to predict results.
- Stop retinoids up to 7 days before a peel. Consider placing the patient on hydroquinone before the chemical peel to decrease the risk of hyperpigmentation.
- Before the procedure, prep the skin with acetone or alcohol. Applying petrolatum helps protect around the eyes, alar crease, and other sensitive areas, “or anywhere you’re concerned about the depth of the peel.”
- Application with rough gauze helps avoid the waste that comes with makeup sponges soaking up the product. It also helps add exfoliation.
- Have everything ready before starting the procedure, including (depending on the peel), a neutralizer or soapless cleanser. Although peels are generally safe, you want to be able to remove one quickly, if needed, without having to leave the room.
- Start with the lowest concentration (salicylic acid or glycolic acid) then titrate up. Ask patients about any reactions they experienced with the previous peel before making the decision on the next concentration.
- For a peel to treat hyperpigmentation, she recommends one peel about every 4 weeks for a series of 5-6 peels.
- After a peel, the patient should use a mineral sunscreen; chemical sunscreens will sting.
Know your comfort zone
Conference chair Pearl Grimes, MD, director of The Vitiligo & Pigmentation Institute of Southern California in Los Angeles, said superficial peels are best for dermatologists new to peeling until they gain comfort with experience.
Superficial and medium-depth peels work well for mild to moderate photoaging, she said at the meeting.
“We know that in darker skin we have more intrinsic aging rather than photoaging. We have more textural changes, hyperpigmentation,” Dr. Grimes said.
For Fitzpatrick skin types I-III, she said, “you can do superficial, medium, and deep peels.” For darker skin types, “I typically stay in the superficial, medium range.”
She said that she uses retinoids to exfoliate before a superficial peel but added, “you’ve got to stop them early because retinoids can make a superficial peel a medium-depth peel.”
Taking photos is important before any procedure, she said, as is spending time with patients clarifying their outcome expectations.
“I love peeling,” Dr. Grimes said. “And it’s cost effective. If you don’t want to spend a ton of money, it’s amazing what you can achieve with chemical peeling.”
When asked by a member of the audience whether they avoid superficial peels in women who are pregnant or breastfeeding, both Dr. Woolery-Lloyd and Dr. Grimes said they do avoid them in those patients.
Dr. Grimes said she tells her patients, especially in the first trimester, “I am the most conservative woman on the planet. I do nothing during the first trimester.”
Dr. Woolery-Lloyd has been a speaker for Ortho Dermatologics, Loreal and EPI, and has done research for Pfizer, Galderma, Allergan, Arcutis, Vyne, Merz, and Eirion. She has been on advisory boards for Loreal, Allergan, Ortho Dermatologics, Pfize,r and Merz. Dr. Grimes reports grant/research Support from Clinuvel Pharmaceuticals, Incyte, Johnson & Johnson, LASEROPTEK, L’Oréal USA, Pfizer, Procter & Gamble, skinbetter science, and Versicolor Technologies, and is on the speakers bureau/receives honoraria for non-CME for Incyte and Procter & Gamble; and is a consultant or is on the advisory board for L’Oréal USA and Procter & Gamble. She has stock options in Versicolor Technologies.
AT THE MEDSCAPE LIVE! PIGMENTARY DISORDERS SYMPOSIUM
Acute diffuse rash on trunk
This patient’s diffusely erythematous and scaly rash, in association with recent antibiotic use, was a classic presentation of a drug eruption. Drug eruptions are adverse cutaneous reactions to various medications; they frequently involve antibiotics and anti-epileptics. They can manifest in a multitude of ways with different morphologies. Medication history and timing to onset of symptoms are paramount in making the diagnosis.
Classic reactions include those that are morbilliform (erythematous macules and papules), lichenoid (violaceous and hyperpigmented papules), exfoliative/erythrodermic, and/or urticarial.1 Petechiae and palpable purpura may also manifest.1 Severe reactions, while less common, must always be considered, given their significant morbidity and mortality. These include2:
- Stevens-Johnson syndrome/toxic epidermal necrolysis with diffuse erythema and areas of denuded, necrotic epidermis,
- Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, and
- Acute, generalized, exanthematous pustulosis (AGEP) consisting of confluent, nonfollicular pustules.
A general principle in the management of drug eruptions is the discontinuation of the offending drug (if known) as soon as possible. If the agent is not known, it is important to discontinue all drugs that are not deemed as essential, particularly medications that are often associated with reactions, such as antibiotics and anti-epileptics. Additionally, evaluation of the oral mucosa, eyes, and genitourinary tract is helpful to diagnose Stevens-Johnson syndrome, if indicated by symptoms or history.
Wound care with cleansing and covering of denuded skin with emollients and wet dressings should be performed. Infections are common complications in these patients due to the increased inflammation, fissuring, and excoriations that accompany the rash, with sepsis from staphylococcal bacteria being the most concerning complication of infection. Additionally, the compromised skin barrier may lead to heat loss and hypothermia, a compensatory hypermetabolism with hyperthermia, and electrolyte imbalances from insensible water losses.2
Most mild eruptions can be treated with topical corticosteroids and antihistamines. However, in severe eruptions, systemic corticosteroids, or referral for immunosuppressive and anticytokine therapies, also should be considered.1
This patient was treated with both a short course of systemic corticosteroids (prednisone 40 mg/d for 5 days, then tapered over 15 days) and topical steroids (triamcinolone 0.1% ointment bid) for symptomatic care. He also was started on an antihistamine (cetirizine 10 mg bid) for itching. Doxycycline and Augmentin were added to his allergy list. At a 1-week follow up, the patient had near resolution of his rash.
Images courtesy of Jose L. Cortez, MD. Text courtesy of Jose L. Cortez, MD, Department of Dermatology, University of New Mexico School of Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.
1. Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003;68:1781-1790.
2. Zhang J, Lei Z, Xu C, et al. Current perspectives on severe drug eruption. Clin Rev Allergy Immunol. 2021;61:282-298. doi: 10.1007/s12016-021-08859-0
This patient’s diffusely erythematous and scaly rash, in association with recent antibiotic use, was a classic presentation of a drug eruption. Drug eruptions are adverse cutaneous reactions to various medications; they frequently involve antibiotics and anti-epileptics. They can manifest in a multitude of ways with different morphologies. Medication history and timing to onset of symptoms are paramount in making the diagnosis.
Classic reactions include those that are morbilliform (erythematous macules and papules), lichenoid (violaceous and hyperpigmented papules), exfoliative/erythrodermic, and/or urticarial.1 Petechiae and palpable purpura may also manifest.1 Severe reactions, while less common, must always be considered, given their significant morbidity and mortality. These include2:
- Stevens-Johnson syndrome/toxic epidermal necrolysis with diffuse erythema and areas of denuded, necrotic epidermis,
- Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, and
- Acute, generalized, exanthematous pustulosis (AGEP) consisting of confluent, nonfollicular pustules.
A general principle in the management of drug eruptions is the discontinuation of the offending drug (if known) as soon as possible. If the agent is not known, it is important to discontinue all drugs that are not deemed as essential, particularly medications that are often associated with reactions, such as antibiotics and anti-epileptics. Additionally, evaluation of the oral mucosa, eyes, and genitourinary tract is helpful to diagnose Stevens-Johnson syndrome, if indicated by symptoms or history.
Wound care with cleansing and covering of denuded skin with emollients and wet dressings should be performed. Infections are common complications in these patients due to the increased inflammation, fissuring, and excoriations that accompany the rash, with sepsis from staphylococcal bacteria being the most concerning complication of infection. Additionally, the compromised skin barrier may lead to heat loss and hypothermia, a compensatory hypermetabolism with hyperthermia, and electrolyte imbalances from insensible water losses.2
Most mild eruptions can be treated with topical corticosteroids and antihistamines. However, in severe eruptions, systemic corticosteroids, or referral for immunosuppressive and anticytokine therapies, also should be considered.1
This patient was treated with both a short course of systemic corticosteroids (prednisone 40 mg/d for 5 days, then tapered over 15 days) and topical steroids (triamcinolone 0.1% ointment bid) for symptomatic care. He also was started on an antihistamine (cetirizine 10 mg bid) for itching. Doxycycline and Augmentin were added to his allergy list. At a 1-week follow up, the patient had near resolution of his rash.
Images courtesy of Jose L. Cortez, MD. Text courtesy of Jose L. Cortez, MD, Department of Dermatology, University of New Mexico School of Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.
This patient’s diffusely erythematous and scaly rash, in association with recent antibiotic use, was a classic presentation of a drug eruption. Drug eruptions are adverse cutaneous reactions to various medications; they frequently involve antibiotics and anti-epileptics. They can manifest in a multitude of ways with different morphologies. Medication history and timing to onset of symptoms are paramount in making the diagnosis.
Classic reactions include those that are morbilliform (erythematous macules and papules), lichenoid (violaceous and hyperpigmented papules), exfoliative/erythrodermic, and/or urticarial.1 Petechiae and palpable purpura may also manifest.1 Severe reactions, while less common, must always be considered, given their significant morbidity and mortality. These include2:
- Stevens-Johnson syndrome/toxic epidermal necrolysis with diffuse erythema and areas of denuded, necrotic epidermis,
- Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, and
- Acute, generalized, exanthematous pustulosis (AGEP) consisting of confluent, nonfollicular pustules.
A general principle in the management of drug eruptions is the discontinuation of the offending drug (if known) as soon as possible. If the agent is not known, it is important to discontinue all drugs that are not deemed as essential, particularly medications that are often associated with reactions, such as antibiotics and anti-epileptics. Additionally, evaluation of the oral mucosa, eyes, and genitourinary tract is helpful to diagnose Stevens-Johnson syndrome, if indicated by symptoms or history.
Wound care with cleansing and covering of denuded skin with emollients and wet dressings should be performed. Infections are common complications in these patients due to the increased inflammation, fissuring, and excoriations that accompany the rash, with sepsis from staphylococcal bacteria being the most concerning complication of infection. Additionally, the compromised skin barrier may lead to heat loss and hypothermia, a compensatory hypermetabolism with hyperthermia, and electrolyte imbalances from insensible water losses.2
Most mild eruptions can be treated with topical corticosteroids and antihistamines. However, in severe eruptions, systemic corticosteroids, or referral for immunosuppressive and anticytokine therapies, also should be considered.1
This patient was treated with both a short course of systemic corticosteroids (prednisone 40 mg/d for 5 days, then tapered over 15 days) and topical steroids (triamcinolone 0.1% ointment bid) for symptomatic care. He also was started on an antihistamine (cetirizine 10 mg bid) for itching. Doxycycline and Augmentin were added to his allergy list. At a 1-week follow up, the patient had near resolution of his rash.
Images courtesy of Jose L. Cortez, MD. Text courtesy of Jose L. Cortez, MD, Department of Dermatology, University of New Mexico School of Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.
1. Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003;68:1781-1790.
2. Zhang J, Lei Z, Xu C, et al. Current perspectives on severe drug eruption. Clin Rev Allergy Immunol. 2021;61:282-298. doi: 10.1007/s12016-021-08859-0
1. Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003;68:1781-1790.
2. Zhang J, Lei Z, Xu C, et al. Current perspectives on severe drug eruption. Clin Rev Allergy Immunol. 2021;61:282-298. doi: 10.1007/s12016-021-08859-0
Cell activity in psoriasis may predict disease severity and provide clues to comorbidities
The activity and clustering of certain cell types may distinguish mild and severe forms of psoriasis, with severe disease altering the cellular and metabolic composition of distal unaffected skin sites, according to a new analysis using single-cell transcriptomic technology.
On the surface, psoriasis severity is identified based on the visible lesions, Rochelle L. Castillo, MD, of the division of rheumatology and the NYU Psoriatic Arthritis Center, NYU Langone Health, New York, and colleagues wrote in their study, published in Science Immunology. Although cellular and molecular features of inflammatory skin diseases such as psoriasis have been characterized, activity at the tissue level and its systemic impact has not been explored.
“Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis, as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease,” study co–senior investigator Jose Scher, MD, director of the Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity at NYU Langone Health, said in a press release accompanying the publication of the findings. “Having found signals with potential systemic consequences, we are now working to understand how skin inflammation can lead to widespread disease affecting other organs,”
In the study, the researchers used spatial transcriptomics, a technique that positions tissue sections onto genetic arrays to determine gene expression by cell type and histological location, helping to create a broad image-based map of where certain cell types are located in tissues and with what other cells they are communicating. They characterized the cell activity of skin samples from 11 men and women with mild to severe psoriasis/psoriatic arthritis, and three healthy adults who did not have psoriasis. They defined the cellular composition of 25 healthy skin biopsies and matched skin biopsies from psoriatic lesional and nonlesional skin, and identified 17 distinct clusters of cells, which they grouped into epidermal, dermis, pilosebaceous, and adipose categories.
The researchers found that cell activity associated with inflammation, as shown by clusters of fibroblasts and dermal macrophages, was more common in the upper layers of the skin in samples from patients with more severe psoriasis, compared with healthy control samples.
They also examined patterns of immune activity at the cellular level and found significant patterns around the upper follicle, around the perifollicular dermis, and within the hair follicle, where immune cells were enriched in healthy skin. Other cells enriched in these upper layer areas in healthy skin included dendritic cells, innate lymphoid cells, T helper cells, T cytotoxic cells, and myeloid cells.
Clusters of fibroblasts and macrophages, which are associated with inflammation, were clustered in psoriatic lesional skin, which also showed more inflammation at the dermal and suprabasal epidermal levels. B lymphocytes also were more prevalent in lesional skin.
The researchers then analyzed the skin samples according to disease severity; mild psoriasis was defined as a Psoriasis Area and Severity Index score less than 12; moderate to severe disease was defined as a PASI score of 12 or higher. The macrophage, fibroblast, and lymphatic endothelium–associated clusters distinguished mild and moderate to severe endotypes.
The pathology of moderate to severe psoriasis in lesional and nonlesional skin showed the extensive effects of psoriasis-related inflammation. Although nonlesional mild disease was clustered with healthy skin, in cases of moderate to severe disease, nonlesional and lesional groups were clustered together. This effect was segregated according to disease severity, independent of the presence of joint disease, and “was particularly evident in distal, nonlesional samples,” the researchers wrote.
The researchers also found evidence of increased gene activity in more than three dozen molecular pathways associated with metabolism and lipid levels in areas of lesional and nonlesional skin, Dr. Scher said.
The findings were limited by several factors including the small sample size and the limits of spatial transcriptomics technology resolution, the researchers wrote. “As this technology evolves, platforms with higher density, and by extension, resolution, of spatially barcoded beads will provide more granularity about cellular microenvironments in healthy and diseased states.”
The study was supported by the National Institutes of Health, the National Psoriasis Foundation, the NYU Colton Center for Autoimmunity, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the Beatrice Snyder Foundation, The Riley Family Foundation, the Rheumatology Research Foundation, and the NY Stem Cell Foundation. Dr. Castillo had no financial conflicts to disclose. Dr. Scher has served as a consultant for Janssen, Abbvie, Novartis, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb, and has received research funding from Janssen and Pfizer.
The activity and clustering of certain cell types may distinguish mild and severe forms of psoriasis, with severe disease altering the cellular and metabolic composition of distal unaffected skin sites, according to a new analysis using single-cell transcriptomic technology.
On the surface, psoriasis severity is identified based on the visible lesions, Rochelle L. Castillo, MD, of the division of rheumatology and the NYU Psoriatic Arthritis Center, NYU Langone Health, New York, and colleagues wrote in their study, published in Science Immunology. Although cellular and molecular features of inflammatory skin diseases such as psoriasis have been characterized, activity at the tissue level and its systemic impact has not been explored.
“Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis, as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease,” study co–senior investigator Jose Scher, MD, director of the Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity at NYU Langone Health, said in a press release accompanying the publication of the findings. “Having found signals with potential systemic consequences, we are now working to understand how skin inflammation can lead to widespread disease affecting other organs,”
In the study, the researchers used spatial transcriptomics, a technique that positions tissue sections onto genetic arrays to determine gene expression by cell type and histological location, helping to create a broad image-based map of where certain cell types are located in tissues and with what other cells they are communicating. They characterized the cell activity of skin samples from 11 men and women with mild to severe psoriasis/psoriatic arthritis, and three healthy adults who did not have psoriasis. They defined the cellular composition of 25 healthy skin biopsies and matched skin biopsies from psoriatic lesional and nonlesional skin, and identified 17 distinct clusters of cells, which they grouped into epidermal, dermis, pilosebaceous, and adipose categories.
The researchers found that cell activity associated with inflammation, as shown by clusters of fibroblasts and dermal macrophages, was more common in the upper layers of the skin in samples from patients with more severe psoriasis, compared with healthy control samples.
They also examined patterns of immune activity at the cellular level and found significant patterns around the upper follicle, around the perifollicular dermis, and within the hair follicle, where immune cells were enriched in healthy skin. Other cells enriched in these upper layer areas in healthy skin included dendritic cells, innate lymphoid cells, T helper cells, T cytotoxic cells, and myeloid cells.
Clusters of fibroblasts and macrophages, which are associated with inflammation, were clustered in psoriatic lesional skin, which also showed more inflammation at the dermal and suprabasal epidermal levels. B lymphocytes also were more prevalent in lesional skin.
The researchers then analyzed the skin samples according to disease severity; mild psoriasis was defined as a Psoriasis Area and Severity Index score less than 12; moderate to severe disease was defined as a PASI score of 12 or higher. The macrophage, fibroblast, and lymphatic endothelium–associated clusters distinguished mild and moderate to severe endotypes.
The pathology of moderate to severe psoriasis in lesional and nonlesional skin showed the extensive effects of psoriasis-related inflammation. Although nonlesional mild disease was clustered with healthy skin, in cases of moderate to severe disease, nonlesional and lesional groups were clustered together. This effect was segregated according to disease severity, independent of the presence of joint disease, and “was particularly evident in distal, nonlesional samples,” the researchers wrote.
The researchers also found evidence of increased gene activity in more than three dozen molecular pathways associated with metabolism and lipid levels in areas of lesional and nonlesional skin, Dr. Scher said.
The findings were limited by several factors including the small sample size and the limits of spatial transcriptomics technology resolution, the researchers wrote. “As this technology evolves, platforms with higher density, and by extension, resolution, of spatially barcoded beads will provide more granularity about cellular microenvironments in healthy and diseased states.”
The study was supported by the National Institutes of Health, the National Psoriasis Foundation, the NYU Colton Center for Autoimmunity, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the Beatrice Snyder Foundation, The Riley Family Foundation, the Rheumatology Research Foundation, and the NY Stem Cell Foundation. Dr. Castillo had no financial conflicts to disclose. Dr. Scher has served as a consultant for Janssen, Abbvie, Novartis, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb, and has received research funding from Janssen and Pfizer.
The activity and clustering of certain cell types may distinguish mild and severe forms of psoriasis, with severe disease altering the cellular and metabolic composition of distal unaffected skin sites, according to a new analysis using single-cell transcriptomic technology.
On the surface, psoriasis severity is identified based on the visible lesions, Rochelle L. Castillo, MD, of the division of rheumatology and the NYU Psoriatic Arthritis Center, NYU Langone Health, New York, and colleagues wrote in their study, published in Science Immunology. Although cellular and molecular features of inflammatory skin diseases such as psoriasis have been characterized, activity at the tissue level and its systemic impact has not been explored.
“Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis, as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease,” study co–senior investigator Jose Scher, MD, director of the Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity at NYU Langone Health, said in a press release accompanying the publication of the findings. “Having found signals with potential systemic consequences, we are now working to understand how skin inflammation can lead to widespread disease affecting other organs,”
In the study, the researchers used spatial transcriptomics, a technique that positions tissue sections onto genetic arrays to determine gene expression by cell type and histological location, helping to create a broad image-based map of where certain cell types are located in tissues and with what other cells they are communicating. They characterized the cell activity of skin samples from 11 men and women with mild to severe psoriasis/psoriatic arthritis, and three healthy adults who did not have psoriasis. They defined the cellular composition of 25 healthy skin biopsies and matched skin biopsies from psoriatic lesional and nonlesional skin, and identified 17 distinct clusters of cells, which they grouped into epidermal, dermis, pilosebaceous, and adipose categories.
The researchers found that cell activity associated with inflammation, as shown by clusters of fibroblasts and dermal macrophages, was more common in the upper layers of the skin in samples from patients with more severe psoriasis, compared with healthy control samples.
They also examined patterns of immune activity at the cellular level and found significant patterns around the upper follicle, around the perifollicular dermis, and within the hair follicle, where immune cells were enriched in healthy skin. Other cells enriched in these upper layer areas in healthy skin included dendritic cells, innate lymphoid cells, T helper cells, T cytotoxic cells, and myeloid cells.
Clusters of fibroblasts and macrophages, which are associated with inflammation, were clustered in psoriatic lesional skin, which also showed more inflammation at the dermal and suprabasal epidermal levels. B lymphocytes also were more prevalent in lesional skin.
The researchers then analyzed the skin samples according to disease severity; mild psoriasis was defined as a Psoriasis Area and Severity Index score less than 12; moderate to severe disease was defined as a PASI score of 12 or higher. The macrophage, fibroblast, and lymphatic endothelium–associated clusters distinguished mild and moderate to severe endotypes.
The pathology of moderate to severe psoriasis in lesional and nonlesional skin showed the extensive effects of psoriasis-related inflammation. Although nonlesional mild disease was clustered with healthy skin, in cases of moderate to severe disease, nonlesional and lesional groups were clustered together. This effect was segregated according to disease severity, independent of the presence of joint disease, and “was particularly evident in distal, nonlesional samples,” the researchers wrote.
The researchers also found evidence of increased gene activity in more than three dozen molecular pathways associated with metabolism and lipid levels in areas of lesional and nonlesional skin, Dr. Scher said.
The findings were limited by several factors including the small sample size and the limits of spatial transcriptomics technology resolution, the researchers wrote. “As this technology evolves, platforms with higher density, and by extension, resolution, of spatially barcoded beads will provide more granularity about cellular microenvironments in healthy and diseased states.”
The study was supported by the National Institutes of Health, the National Psoriasis Foundation, the NYU Colton Center for Autoimmunity, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the Beatrice Snyder Foundation, The Riley Family Foundation, the Rheumatology Research Foundation, and the NY Stem Cell Foundation. Dr. Castillo had no financial conflicts to disclose. Dr. Scher has served as a consultant for Janssen, Abbvie, Novartis, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb, and has received research funding from Janssen and Pfizer.
FROM SCIENCE IMMUNOLOGY
Lower racial disparity in melanoma diagnoses in vets than U.S. men overall, study finds
a new analysis shows.
“The trend of a lower racial disparity in the VA in the proportion of melanomas with local disease and in the proportion of distant metastasis at presentation was observed across age groups,” wrote Martin A. Weinstock MD, PhD, and Rachel K. Lim, of the department of dermatology at Brown University, Providence, R.I., and the Center for Dermatoepidemiology at the VA Providence Healthcare System. The study was published online in the Journal of the American Academy of Dermatology.
“Melanoma was the fourth-most common cancer [diagnosed] in male VA patients in 2010,” wrote the authors, who also pointed out that “prior surveys found that 11%-13% of U.S. active-duty personnel routinely use sunscreen despite significant occupational sun exposure. Racial disparities are important concerns in the VA and elsewhere.”
To compare the stage of melanoma at presentation among White and non-Whites patients in the VA and in the general U.S. population, the researchers identified invasive cutaneous melanoma cases from 2000 to 2019 in the VA Corporate Data Warehouse and the Surveillance, Epidemiology and End Results Program (SEER).
They restricted the analysis to men because of the small proportion of women in the at-risk veteran population and excluded cases with an age younger than 20, those with unknown histology, and melanoma in situ. The researchers performed two-tailed z-tests to evaluate the difference in proportions of melanoma stages between the veteran population and the general population.
The analysis included 44,077 cases of invasive melanoma in the VA and 217,030 in SEER. Racial disparities in melanoma staging were substantially less pronounced in the VA than in SEER.
In the VA, localized disease represented 77.9% of melanomas among Whites versus 71.0% among non-Whites. But in SEER, localized disease represented 80.7% of melanomas among Whites versus 61.5% in non-Whites – over double the VA disparity (P < .0001).
Likewise, the disparity between Whites and nonwhites observed for regional or distant metastatic disease at presentation in the VA was lower than the disparity observed in SEER. For example, in the VA, distant metastatic disease at presentation represented 6.1% of melanomas among Whites versus 8.6% among non-Whites, while in SEER it represented 4.8% of melanomas among Whites versus 11.3% in non-Whites – again, more than double the VA disparity (P < .0001).
“These differences between the VA and SEER were less marked” among those older than 65 years, the researchers wrote. “Notably, the differences between VA and SEER in racial disparities among those greater than 65 in age were still significant for localized disease and for distant metastasis.”
The findings suggest that the VA “may be more effective in reducing racial disparities in melanoma stage at diagnosis, potentially due to all patients in the VA dataset having insured access to health care, regardless of socioeconomic status,” the researchers concluded. Similarly, the decreased difference in racial disparities observed in patients older than 65 across systems “may be related to the availability of Medicare to the older general populations. The authors acknowledged several study limitations, such as the predominantly elderly and male VA population, potentially underreported utilization of non-VA dermatologic care, and variation in geographic regions covered by each database.
Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, who was asked to comment on the work, said in an interview he would have liked to see a more detailed breakdown of the younger patients, “for those in their 30s and 40s, to see if this trend held up.”
He would have also liked to see how the data trended over time, adding, “while this, broadly, may be good news for our veterans, attributing this finding to a reduction in access disparity or some other organizational intervention seems a little premature. Regardless, Dr. Weinstock has given us, once again, information from our veterans to probe for the betterment of all patients.”
The researchers reported having no relevant disclosures and the study had no funding. Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.
a new analysis shows.
“The trend of a lower racial disparity in the VA in the proportion of melanomas with local disease and in the proportion of distant metastasis at presentation was observed across age groups,” wrote Martin A. Weinstock MD, PhD, and Rachel K. Lim, of the department of dermatology at Brown University, Providence, R.I., and the Center for Dermatoepidemiology at the VA Providence Healthcare System. The study was published online in the Journal of the American Academy of Dermatology.
“Melanoma was the fourth-most common cancer [diagnosed] in male VA patients in 2010,” wrote the authors, who also pointed out that “prior surveys found that 11%-13% of U.S. active-duty personnel routinely use sunscreen despite significant occupational sun exposure. Racial disparities are important concerns in the VA and elsewhere.”
To compare the stage of melanoma at presentation among White and non-Whites patients in the VA and in the general U.S. population, the researchers identified invasive cutaneous melanoma cases from 2000 to 2019 in the VA Corporate Data Warehouse and the Surveillance, Epidemiology and End Results Program (SEER).
They restricted the analysis to men because of the small proportion of women in the at-risk veteran population and excluded cases with an age younger than 20, those with unknown histology, and melanoma in situ. The researchers performed two-tailed z-tests to evaluate the difference in proportions of melanoma stages between the veteran population and the general population.
The analysis included 44,077 cases of invasive melanoma in the VA and 217,030 in SEER. Racial disparities in melanoma staging were substantially less pronounced in the VA than in SEER.
In the VA, localized disease represented 77.9% of melanomas among Whites versus 71.0% among non-Whites. But in SEER, localized disease represented 80.7% of melanomas among Whites versus 61.5% in non-Whites – over double the VA disparity (P < .0001).
Likewise, the disparity between Whites and nonwhites observed for regional or distant metastatic disease at presentation in the VA was lower than the disparity observed in SEER. For example, in the VA, distant metastatic disease at presentation represented 6.1% of melanomas among Whites versus 8.6% among non-Whites, while in SEER it represented 4.8% of melanomas among Whites versus 11.3% in non-Whites – again, more than double the VA disparity (P < .0001).
“These differences between the VA and SEER were less marked” among those older than 65 years, the researchers wrote. “Notably, the differences between VA and SEER in racial disparities among those greater than 65 in age were still significant for localized disease and for distant metastasis.”
The findings suggest that the VA “may be more effective in reducing racial disparities in melanoma stage at diagnosis, potentially due to all patients in the VA dataset having insured access to health care, regardless of socioeconomic status,” the researchers concluded. Similarly, the decreased difference in racial disparities observed in patients older than 65 across systems “may be related to the availability of Medicare to the older general populations. The authors acknowledged several study limitations, such as the predominantly elderly and male VA population, potentially underreported utilization of non-VA dermatologic care, and variation in geographic regions covered by each database.
Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, who was asked to comment on the work, said in an interview he would have liked to see a more detailed breakdown of the younger patients, “for those in their 30s and 40s, to see if this trend held up.”
He would have also liked to see how the data trended over time, adding, “while this, broadly, may be good news for our veterans, attributing this finding to a reduction in access disparity or some other organizational intervention seems a little premature. Regardless, Dr. Weinstock has given us, once again, information from our veterans to probe for the betterment of all patients.”
The researchers reported having no relevant disclosures and the study had no funding. Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.
a new analysis shows.
“The trend of a lower racial disparity in the VA in the proportion of melanomas with local disease and in the proportion of distant metastasis at presentation was observed across age groups,” wrote Martin A. Weinstock MD, PhD, and Rachel K. Lim, of the department of dermatology at Brown University, Providence, R.I., and the Center for Dermatoepidemiology at the VA Providence Healthcare System. The study was published online in the Journal of the American Academy of Dermatology.
“Melanoma was the fourth-most common cancer [diagnosed] in male VA patients in 2010,” wrote the authors, who also pointed out that “prior surveys found that 11%-13% of U.S. active-duty personnel routinely use sunscreen despite significant occupational sun exposure. Racial disparities are important concerns in the VA and elsewhere.”
To compare the stage of melanoma at presentation among White and non-Whites patients in the VA and in the general U.S. population, the researchers identified invasive cutaneous melanoma cases from 2000 to 2019 in the VA Corporate Data Warehouse and the Surveillance, Epidemiology and End Results Program (SEER).
They restricted the analysis to men because of the small proportion of women in the at-risk veteran population and excluded cases with an age younger than 20, those with unknown histology, and melanoma in situ. The researchers performed two-tailed z-tests to evaluate the difference in proportions of melanoma stages between the veteran population and the general population.
The analysis included 44,077 cases of invasive melanoma in the VA and 217,030 in SEER. Racial disparities in melanoma staging were substantially less pronounced in the VA than in SEER.
In the VA, localized disease represented 77.9% of melanomas among Whites versus 71.0% among non-Whites. But in SEER, localized disease represented 80.7% of melanomas among Whites versus 61.5% in non-Whites – over double the VA disparity (P < .0001).
Likewise, the disparity between Whites and nonwhites observed for regional or distant metastatic disease at presentation in the VA was lower than the disparity observed in SEER. For example, in the VA, distant metastatic disease at presentation represented 6.1% of melanomas among Whites versus 8.6% among non-Whites, while in SEER it represented 4.8% of melanomas among Whites versus 11.3% in non-Whites – again, more than double the VA disparity (P < .0001).
“These differences between the VA and SEER were less marked” among those older than 65 years, the researchers wrote. “Notably, the differences between VA and SEER in racial disparities among those greater than 65 in age were still significant for localized disease and for distant metastasis.”
The findings suggest that the VA “may be more effective in reducing racial disparities in melanoma stage at diagnosis, potentially due to all patients in the VA dataset having insured access to health care, regardless of socioeconomic status,” the researchers concluded. Similarly, the decreased difference in racial disparities observed in patients older than 65 across systems “may be related to the availability of Medicare to the older general populations. The authors acknowledged several study limitations, such as the predominantly elderly and male VA population, potentially underreported utilization of non-VA dermatologic care, and variation in geographic regions covered by each database.
Travis W. Blalock, MD, director of dermatologic surgery, Mohs micrographic surgery, and cutaneous oncology at Emory University, Atlanta, who was asked to comment on the work, said in an interview he would have liked to see a more detailed breakdown of the younger patients, “for those in their 30s and 40s, to see if this trend held up.”
He would have also liked to see how the data trended over time, adding, “while this, broadly, may be good news for our veterans, attributing this finding to a reduction in access disparity or some other organizational intervention seems a little premature. Regardless, Dr. Weinstock has given us, once again, information from our veterans to probe for the betterment of all patients.”
The researchers reported having no relevant disclosures and the study had no funding. Dr. Blalock disclosed that he has served as a principal investigator for Castle Biosciences.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Abrocitinib remains effective at 96 weeks, in older as well as younger adults
WASHINGTON – A substantial proportion of , Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.
The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.
At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.
An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.
The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.
The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.
Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
IGA, PP-NRS, and DLQI results
At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.
The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.
Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.
Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.
The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.
Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.
In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.
It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.
Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”
Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.
WASHINGTON – A substantial proportion of , Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.
The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.
At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.
An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.
The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.
The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.
Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
IGA, PP-NRS, and DLQI results
At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.
The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.
Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.
Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.
The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.
Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.
In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.
It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.
Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”
Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.
WASHINGTON – A substantial proportion of , Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.
The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.
At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.
An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.
The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.
The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.
Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
IGA, PP-NRS, and DLQI results
At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.
The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.
Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.
Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.
The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.
Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.
In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.
It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.
Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”
Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.
AT RAD 2023
IL-17 inhibitor approved in Europe for hidradenitis suppurativa
The biologic is the first interleukin-17A (IL-17A) inhibitor to be approved for the treatment of moderate to severe HS. The manufacturer, Novartis, expects a regulatory decision from the U.S. Food and Drug Administration later this year, according to a company press release announcing the approval.
The European approval is based on the results from the phase 3 SUNSHINE and SUNRISE trials, which evaluated the efficacy, safety, and tolerability of the drug. The multicenter, randomized, placebo-controlled, double-blind trials enrolled a total of more than 1,000 adults with moderate to severe HS.
Patients were randomly assigned either to receive subcutaneous secukinumab 300 mg every 2 weeks or 4 weeks or to receive placebo. The treatment was effective at improving the symptoms of HS when given every 2 weeks, according to results recently published in The Lancet.
The primary outcome measure for both trials was HS clinical response – defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or draining fistulae, compared with baseline.
In the studies, 42% and 45% of patients treated with secukinumab every 2 weeks in the SUNRISE and SUNSHINE trials, respectively, had a clinical response at 16 weeks, compared with 31% and 34% among those who received placebo, which were statistically significant differences. A significant clinical response was seen at week 4 in the SUNSHINE trial and in week 2 in the SUNRISE trial. In both trials, clinical efficacy was sustained to the end of the trial, at week 52.
Headaches were the most common side effect. They affected approximately 1 in 10 patients in both trials.
HS, also called acne inversa, is a chronic skin condition that causes painful lesions. The condition affects 1%- 2% of the U.S. population, according to the nonprofit Hidradenitis Suppurativa Foundation. It also disproportionately affects young adults, women, and Black patients.
In Europe, about 200,000 people live with moderate to severe stages of the condition, according to the Novartis press release.
Secukinumab inhibits IL-17A, a cytokine involved in the inflammation of psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and nonradiographic axial spondylarthritis. It has been approved for the treatment of those conditions, as well as for the treatment of juvenile idiopathic arthritis and enthesitis-related arthritis in the United States and the European Union.
The only other approved biologic therapy for HS is the tumor necrosis factor inhibitor adalimumab.
Novartis is investigating the potential application of secukinumab for the treatment of lupus nephritis and giant cell arteritis, as well as polymyalgia rheumatica and rotator cuff tendinopathy, according to the company press release.
The study published in The Lancet was funded by Novartis.
A version of this article first appeared on Medscape.com.
The biologic is the first interleukin-17A (IL-17A) inhibitor to be approved for the treatment of moderate to severe HS. The manufacturer, Novartis, expects a regulatory decision from the U.S. Food and Drug Administration later this year, according to a company press release announcing the approval.
The European approval is based on the results from the phase 3 SUNSHINE and SUNRISE trials, which evaluated the efficacy, safety, and tolerability of the drug. The multicenter, randomized, placebo-controlled, double-blind trials enrolled a total of more than 1,000 adults with moderate to severe HS.
Patients were randomly assigned either to receive subcutaneous secukinumab 300 mg every 2 weeks or 4 weeks or to receive placebo. The treatment was effective at improving the symptoms of HS when given every 2 weeks, according to results recently published in The Lancet.
The primary outcome measure for both trials was HS clinical response – defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or draining fistulae, compared with baseline.
In the studies, 42% and 45% of patients treated with secukinumab every 2 weeks in the SUNRISE and SUNSHINE trials, respectively, had a clinical response at 16 weeks, compared with 31% and 34% among those who received placebo, which were statistically significant differences. A significant clinical response was seen at week 4 in the SUNSHINE trial and in week 2 in the SUNRISE trial. In both trials, clinical efficacy was sustained to the end of the trial, at week 52.
Headaches were the most common side effect. They affected approximately 1 in 10 patients in both trials.
HS, also called acne inversa, is a chronic skin condition that causes painful lesions. The condition affects 1%- 2% of the U.S. population, according to the nonprofit Hidradenitis Suppurativa Foundation. It also disproportionately affects young adults, women, and Black patients.
In Europe, about 200,000 people live with moderate to severe stages of the condition, according to the Novartis press release.
Secukinumab inhibits IL-17A, a cytokine involved in the inflammation of psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and nonradiographic axial spondylarthritis. It has been approved for the treatment of those conditions, as well as for the treatment of juvenile idiopathic arthritis and enthesitis-related arthritis in the United States and the European Union.
The only other approved biologic therapy for HS is the tumor necrosis factor inhibitor adalimumab.
Novartis is investigating the potential application of secukinumab for the treatment of lupus nephritis and giant cell arteritis, as well as polymyalgia rheumatica and rotator cuff tendinopathy, according to the company press release.
The study published in The Lancet was funded by Novartis.
A version of this article first appeared on Medscape.com.
The biologic is the first interleukin-17A (IL-17A) inhibitor to be approved for the treatment of moderate to severe HS. The manufacturer, Novartis, expects a regulatory decision from the U.S. Food and Drug Administration later this year, according to a company press release announcing the approval.
The European approval is based on the results from the phase 3 SUNSHINE and SUNRISE trials, which evaluated the efficacy, safety, and tolerability of the drug. The multicenter, randomized, placebo-controlled, double-blind trials enrolled a total of more than 1,000 adults with moderate to severe HS.
Patients were randomly assigned either to receive subcutaneous secukinumab 300 mg every 2 weeks or 4 weeks or to receive placebo. The treatment was effective at improving the symptoms of HS when given every 2 weeks, according to results recently published in The Lancet.
The primary outcome measure for both trials was HS clinical response – defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or draining fistulae, compared with baseline.
In the studies, 42% and 45% of patients treated with secukinumab every 2 weeks in the SUNRISE and SUNSHINE trials, respectively, had a clinical response at 16 weeks, compared with 31% and 34% among those who received placebo, which were statistically significant differences. A significant clinical response was seen at week 4 in the SUNSHINE trial and in week 2 in the SUNRISE trial. In both trials, clinical efficacy was sustained to the end of the trial, at week 52.
Headaches were the most common side effect. They affected approximately 1 in 10 patients in both trials.
HS, also called acne inversa, is a chronic skin condition that causes painful lesions. The condition affects 1%- 2% of the U.S. population, according to the nonprofit Hidradenitis Suppurativa Foundation. It also disproportionately affects young adults, women, and Black patients.
In Europe, about 200,000 people live with moderate to severe stages of the condition, according to the Novartis press release.
Secukinumab inhibits IL-17A, a cytokine involved in the inflammation of psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and nonradiographic axial spondylarthritis. It has been approved for the treatment of those conditions, as well as for the treatment of juvenile idiopathic arthritis and enthesitis-related arthritis in the United States and the European Union.
The only other approved biologic therapy for HS is the tumor necrosis factor inhibitor adalimumab.
Novartis is investigating the potential application of secukinumab for the treatment of lupus nephritis and giant cell arteritis, as well as polymyalgia rheumatica and rotator cuff tendinopathy, according to the company press release.
The study published in The Lancet was funded by Novartis.
A version of this article first appeared on Medscape.com.
Dupilumab outcomes stable at end of open label atopic dermatitis study
WASHINGTON – The and no new emergent side effects, Lisa Beck, MD, reported during a late-breaking session at the annual Revolutionizing Atopic Dermatitis conference.
Other recent research on the biologic has shown that it improves lesional skin barrier function and rapidly reduces the abundance of Staphylococcus aureus on lesional skin, Dr. Beck, professor of dermatology at the University of Rochester (N.Y.), said during another session at the meeting on long-term control of AD. Dr. Beck directs a laboratory at the University of Rochester Medical Center that focuses on understanding AD and is involved in the National Institute of Allergy and Infectious Diseases (NIAID)-funded Atopic Dermatitis Research Network (ADRN).
The LIBERTY AD open-label extension (OLE) study was a phase 3 trial of 2,677 adults with moderate to severe AD who had participated in previous dupilumab clinical trials and were treated with 300 mg dupilumab weekly or every other week. Concomitant treatments were permitted, including topical corticosteroids and topical calcineurin inhibitors. (The proportion of patients dosed on an every-other-week or weekly dosing schedule was not available.)
Of 334 patients (12.5%) who remained in the trial at week 260, or 5 years, 88.9% achieved at least a 75% improvement in lesion extent and severity (Eczema Area and Severity Index [EASI]-75), and 76.2% achieved an EASI-90. The proportion achieving at least a 4-point reduction in the Peak Pruritus Numerical Rating Scale (NRS) or a score of 0 was 66.5%. At 5 years, improvements “seem very stable,” with “no loss in efficacy,” Dr. Beck said.
The majority of patients who withdrew from the open-label extension trial did so because the study was terminated at their site or because of the drug’s approval and commercialization – not for a medical reason, Dr. Beck said. Over the course of the extension trial, 4% of those enrolled withdrew because of adverse events and about 2% withdrew because of lack of efficacy.
Safety of dupilumab
The extension trial lacked a control arm, so Dr. Beck and her colleagues compared safety results to those in the final data set for patients in the LIBERTY AD CHRONOS study who received dupilumab 300 mg weekly with concomitant corticosteroids. The CHRONOS study was a 1-year randomized, double-blinded placebo-controlled phase 3 trial.
The exposure-adjusted incidence rate of severe treatment-emergent adverse events (TEAE) was lower at the close of the extension trial (5 patients/100 patient years [PY]) than at the end of the CHRONOS study (5.9 patients/100 PY). The incidence of serious adverse events related to treatment was 0.6 patients/100 PY in the final open label extension study data set, compared with 0.7 patients/100 PY in the CHRONOS final data set.
Adverse event rates “are really, if anything, slightly less in the OLE study versus the CHRONOS study, which was 1 year of treatment,” Dr. Beck said. And “no new adverse events have emerged.”
During a question and answer period, Dr. Beck pointed out that existing and future “real world” registries of patients on dupilumab and other new therapies will better inform dermatologists of adverse events than clinical trials have done.
Ocular surface disease
In a separate presentation on the safety of biologics, Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, said that in routine care, ocular surface disease is the most predominant side effect associated with dupilumab. “We don’t know the mechanism of action. But it’s not infectious, it’s not pink eye, and importantly, it’s not allergic conjunctivitis,” he said, noting that the spectrum of disease ranges from dry eye and eye itching to “frank conjunctivitis” and keratitis.
Most cases are mild to moderate and can often be managed with lubricating eye drops and periodic use of corticosteroid eye drops. Co-management with an ophthalmologist is often advisable, he said.
Dupilumab-associated erythema/eczema of the face was “not seen much” in clinical trials but is also being reported in the literature, largely by European researchers, Dr. Blauvelt said. “We hear a lot about red face, but I don’t think it’s much of an issue,” he said. “Most of the time, in my experience, it will [reflect] breakthrough residual AD, and I like to treat it with non-steroidal topicals.”
Occasionally, the withdrawal of steroids or allergic contact dermatitis are at play, Dr. Blauvelt said. “If you see red face in a person on dupilumab, use your clinical prowess, do a differential diagnosis, and treat accordingly.”
Effect on S. aureus
The vast majority of adults with moderate to severe AD have skin colonization with S. aureus, Dr. Beck said during the session on long-term control of AD. The presence of S. aureus in skin cultures correlates strongly with AD severity, type 2 immunity polarization, skin barrier disruption, and allergen sensitization, she said.
“So if we could do something to get rid of the staph and keep it away, one might imagine that would help” control the AD disease process, she said.
An ADRN study evaluated S. aureus in the skin of 71 patients who were randomized to receive dupilumab or placebo and found a “profound” effect of the biologic. “We were truly shocked by how quickly we saw a reduction in Staph aureus ... in lesional skin as early as 3 days” into treatment with dupilumab, she said of the unpublished findings. “And there is a pretty nice association with improvement in disease severity.”
Dr. Beck reported consultancy/advisory board work with Regeneron, Sanofi/Genzyme, among other disclosures. Dr. Blauvelt reported consultancy/advisory board work for Regeneron and Sanofi Genzyme and has received speakers bureau/honoraria for non-CME work for Regeneron and Sanofi, among other disclosures.
WASHINGTON – The and no new emergent side effects, Lisa Beck, MD, reported during a late-breaking session at the annual Revolutionizing Atopic Dermatitis conference.
Other recent research on the biologic has shown that it improves lesional skin barrier function and rapidly reduces the abundance of Staphylococcus aureus on lesional skin, Dr. Beck, professor of dermatology at the University of Rochester (N.Y.), said during another session at the meeting on long-term control of AD. Dr. Beck directs a laboratory at the University of Rochester Medical Center that focuses on understanding AD and is involved in the National Institute of Allergy and Infectious Diseases (NIAID)-funded Atopic Dermatitis Research Network (ADRN).
The LIBERTY AD open-label extension (OLE) study was a phase 3 trial of 2,677 adults with moderate to severe AD who had participated in previous dupilumab clinical trials and were treated with 300 mg dupilumab weekly or every other week. Concomitant treatments were permitted, including topical corticosteroids and topical calcineurin inhibitors. (The proportion of patients dosed on an every-other-week or weekly dosing schedule was not available.)
Of 334 patients (12.5%) who remained in the trial at week 260, or 5 years, 88.9% achieved at least a 75% improvement in lesion extent and severity (Eczema Area and Severity Index [EASI]-75), and 76.2% achieved an EASI-90. The proportion achieving at least a 4-point reduction in the Peak Pruritus Numerical Rating Scale (NRS) or a score of 0 was 66.5%. At 5 years, improvements “seem very stable,” with “no loss in efficacy,” Dr. Beck said.
The majority of patients who withdrew from the open-label extension trial did so because the study was terminated at their site or because of the drug’s approval and commercialization – not for a medical reason, Dr. Beck said. Over the course of the extension trial, 4% of those enrolled withdrew because of adverse events and about 2% withdrew because of lack of efficacy.
Safety of dupilumab
The extension trial lacked a control arm, so Dr. Beck and her colleagues compared safety results to those in the final data set for patients in the LIBERTY AD CHRONOS study who received dupilumab 300 mg weekly with concomitant corticosteroids. The CHRONOS study was a 1-year randomized, double-blinded placebo-controlled phase 3 trial.
The exposure-adjusted incidence rate of severe treatment-emergent adverse events (TEAE) was lower at the close of the extension trial (5 patients/100 patient years [PY]) than at the end of the CHRONOS study (5.9 patients/100 PY). The incidence of serious adverse events related to treatment was 0.6 patients/100 PY in the final open label extension study data set, compared with 0.7 patients/100 PY in the CHRONOS final data set.
Adverse event rates “are really, if anything, slightly less in the OLE study versus the CHRONOS study, which was 1 year of treatment,” Dr. Beck said. And “no new adverse events have emerged.”
During a question and answer period, Dr. Beck pointed out that existing and future “real world” registries of patients on dupilumab and other new therapies will better inform dermatologists of adverse events than clinical trials have done.
Ocular surface disease
In a separate presentation on the safety of biologics, Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, said that in routine care, ocular surface disease is the most predominant side effect associated with dupilumab. “We don’t know the mechanism of action. But it’s not infectious, it’s not pink eye, and importantly, it’s not allergic conjunctivitis,” he said, noting that the spectrum of disease ranges from dry eye and eye itching to “frank conjunctivitis” and keratitis.
Most cases are mild to moderate and can often be managed with lubricating eye drops and periodic use of corticosteroid eye drops. Co-management with an ophthalmologist is often advisable, he said.
Dupilumab-associated erythema/eczema of the face was “not seen much” in clinical trials but is also being reported in the literature, largely by European researchers, Dr. Blauvelt said. “We hear a lot about red face, but I don’t think it’s much of an issue,” he said. “Most of the time, in my experience, it will [reflect] breakthrough residual AD, and I like to treat it with non-steroidal topicals.”
Occasionally, the withdrawal of steroids or allergic contact dermatitis are at play, Dr. Blauvelt said. “If you see red face in a person on dupilumab, use your clinical prowess, do a differential diagnosis, and treat accordingly.”
Effect on S. aureus
The vast majority of adults with moderate to severe AD have skin colonization with S. aureus, Dr. Beck said during the session on long-term control of AD. The presence of S. aureus in skin cultures correlates strongly with AD severity, type 2 immunity polarization, skin barrier disruption, and allergen sensitization, she said.
“So if we could do something to get rid of the staph and keep it away, one might imagine that would help” control the AD disease process, she said.
An ADRN study evaluated S. aureus in the skin of 71 patients who were randomized to receive dupilumab or placebo and found a “profound” effect of the biologic. “We were truly shocked by how quickly we saw a reduction in Staph aureus ... in lesional skin as early as 3 days” into treatment with dupilumab, she said of the unpublished findings. “And there is a pretty nice association with improvement in disease severity.”
Dr. Beck reported consultancy/advisory board work with Regeneron, Sanofi/Genzyme, among other disclosures. Dr. Blauvelt reported consultancy/advisory board work for Regeneron and Sanofi Genzyme and has received speakers bureau/honoraria for non-CME work for Regeneron and Sanofi, among other disclosures.
WASHINGTON – The and no new emergent side effects, Lisa Beck, MD, reported during a late-breaking session at the annual Revolutionizing Atopic Dermatitis conference.
Other recent research on the biologic has shown that it improves lesional skin barrier function and rapidly reduces the abundance of Staphylococcus aureus on lesional skin, Dr. Beck, professor of dermatology at the University of Rochester (N.Y.), said during another session at the meeting on long-term control of AD. Dr. Beck directs a laboratory at the University of Rochester Medical Center that focuses on understanding AD and is involved in the National Institute of Allergy and Infectious Diseases (NIAID)-funded Atopic Dermatitis Research Network (ADRN).
The LIBERTY AD open-label extension (OLE) study was a phase 3 trial of 2,677 adults with moderate to severe AD who had participated in previous dupilumab clinical trials and were treated with 300 mg dupilumab weekly or every other week. Concomitant treatments were permitted, including topical corticosteroids and topical calcineurin inhibitors. (The proportion of patients dosed on an every-other-week or weekly dosing schedule was not available.)
Of 334 patients (12.5%) who remained in the trial at week 260, or 5 years, 88.9% achieved at least a 75% improvement in lesion extent and severity (Eczema Area and Severity Index [EASI]-75), and 76.2% achieved an EASI-90. The proportion achieving at least a 4-point reduction in the Peak Pruritus Numerical Rating Scale (NRS) or a score of 0 was 66.5%. At 5 years, improvements “seem very stable,” with “no loss in efficacy,” Dr. Beck said.
The majority of patients who withdrew from the open-label extension trial did so because the study was terminated at their site or because of the drug’s approval and commercialization – not for a medical reason, Dr. Beck said. Over the course of the extension trial, 4% of those enrolled withdrew because of adverse events and about 2% withdrew because of lack of efficacy.
Safety of dupilumab
The extension trial lacked a control arm, so Dr. Beck and her colleagues compared safety results to those in the final data set for patients in the LIBERTY AD CHRONOS study who received dupilumab 300 mg weekly with concomitant corticosteroids. The CHRONOS study was a 1-year randomized, double-blinded placebo-controlled phase 3 trial.
The exposure-adjusted incidence rate of severe treatment-emergent adverse events (TEAE) was lower at the close of the extension trial (5 patients/100 patient years [PY]) than at the end of the CHRONOS study (5.9 patients/100 PY). The incidence of serious adverse events related to treatment was 0.6 patients/100 PY in the final open label extension study data set, compared with 0.7 patients/100 PY in the CHRONOS final data set.
Adverse event rates “are really, if anything, slightly less in the OLE study versus the CHRONOS study, which was 1 year of treatment,” Dr. Beck said. And “no new adverse events have emerged.”
During a question and answer period, Dr. Beck pointed out that existing and future “real world” registries of patients on dupilumab and other new therapies will better inform dermatologists of adverse events than clinical trials have done.
Ocular surface disease
In a separate presentation on the safety of biologics, Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, said that in routine care, ocular surface disease is the most predominant side effect associated with dupilumab. “We don’t know the mechanism of action. But it’s not infectious, it’s not pink eye, and importantly, it’s not allergic conjunctivitis,” he said, noting that the spectrum of disease ranges from dry eye and eye itching to “frank conjunctivitis” and keratitis.
Most cases are mild to moderate and can often be managed with lubricating eye drops and periodic use of corticosteroid eye drops. Co-management with an ophthalmologist is often advisable, he said.
Dupilumab-associated erythema/eczema of the face was “not seen much” in clinical trials but is also being reported in the literature, largely by European researchers, Dr. Blauvelt said. “We hear a lot about red face, but I don’t think it’s much of an issue,” he said. “Most of the time, in my experience, it will [reflect] breakthrough residual AD, and I like to treat it with non-steroidal topicals.”
Occasionally, the withdrawal of steroids or allergic contact dermatitis are at play, Dr. Blauvelt said. “If you see red face in a person on dupilumab, use your clinical prowess, do a differential diagnosis, and treat accordingly.”
Effect on S. aureus
The vast majority of adults with moderate to severe AD have skin colonization with S. aureus, Dr. Beck said during the session on long-term control of AD. The presence of S. aureus in skin cultures correlates strongly with AD severity, type 2 immunity polarization, skin barrier disruption, and allergen sensitization, she said.
“So if we could do something to get rid of the staph and keep it away, one might imagine that would help” control the AD disease process, she said.
An ADRN study evaluated S. aureus in the skin of 71 patients who were randomized to receive dupilumab or placebo and found a “profound” effect of the biologic. “We were truly shocked by how quickly we saw a reduction in Staph aureus ... in lesional skin as early as 3 days” into treatment with dupilumab, she said of the unpublished findings. “And there is a pretty nice association with improvement in disease severity.”
Dr. Beck reported consultancy/advisory board work with Regeneron, Sanofi/Genzyme, among other disclosures. Dr. Blauvelt reported consultancy/advisory board work for Regeneron and Sanofi Genzyme and has received speakers bureau/honoraria for non-CME work for Regeneron and Sanofi, among other disclosures.
AT RAD 2023
EULAR systemic sclerosis recommendations now include immunosuppressants
MILAN – Targeted synthetic and biologic therapies are recommended as disease-modifying agents for key fibrotic manifestations of systemic sclerosis for the first time in the 2023 update of European Alliance of Associations for Rheumatology recommendations for the treatment of systemic sclerosis.
Reflecting important advances over the past 8 years, mostly relating to the use of new treatments being made available to patients, the recommendations provide an update on the 2017 recommendations, which relied on evidence published through 2014. Of note, these include the use of immunosuppressive agents, for example, the monoclonal antibody rituximab (Rituxan) for skin and lung fibrosis.
“For the first time, synthetic and targeted treatments are recommended for the treatment of systemic sclerosis–interstitial lung disease, including mycophenolate mofetil [Cellcept], nintedanib [Ofev], rituximab, and tocilizumab [Actemra]. None of these were present in 2017. Mycophenolate mofetil is also recommended for the treatment of skin fibrosis, and this was not present in 2017,” Francesco Del Galdo, MD, rheumatology consultant at Leeds Teaching Hospital NHS Trust, Leeds, England, and member of the 2023 recommendations task force, said in an interview. He gave an overview of the preliminary recommendations at the annual European Congress of Rheumatology.
“Phosphodiesterase-5 [PDE-5] inhibitors and endothelin receptor antagonist [ERA] monotherapy are also recommended for up-front combination use for digital ulcers and pulmonary hypertension, and this is new for 2023 and was not present in the 2017 recommendations,” Dr. Del Galdo added.
The new recommendations also note that iloprost is categorized as having grade A evidence for use in Raynaud’s phenomenon and digital ulcers, while it has grade B evidence for pulmonary hypertension.
“We are not allowed to share the final table [of recommendations] today because the wording has only very recently been agreed” upon, Dr. Del Galdo said, but he provided a summary representation and reflected on some changes, noting that the task force is aiming to publish the 2023 recommendations by the end of the year.
Consideration and discussion of both established and new evidence highlighted a need for more evidence on the use of immunosuppressive agents in vascular manifestations of systemic sclerosis, as well as for gastrointestinal and musculoskeletal ones.
In this update to the 2017 recommendations, high-grade evidence was identified for use of immunosuppressants in skin and lung fibrosis. Grade A evidence has been accepted for the use of rituximab in skin fibrosis; for interstitial lung disease, rituximab, cyclophosphamide, and nintedanib also have grade A evidence, which is a change from the 2017 recommendations.
A total of 20 updated recommendations were agreed on, an increase from 16 in 2017. These were grouped into eight disease domains: Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, skin fibrosis, interstitial lung disease, musculoskeletal and gastrointestinal manifestations, and renal crisis. Interventions were then graded A-D based on the evidence reviewed.
“This approach allowed us to see clearly that there were patterns of similar recommendations in different organ manifestations, reflecting an understanding of common pathogenic pathways,” said Dr. Del Galdo.
He also noted that the development of the recommendations highlighted certain gaps in research that limit treatment options. “By grouping the recommendations in blocks – for example, skin fibrosis or vascular [manifestations] – we show that immunosuppressive treatments have only been studied in skin and lung, while vascular manifestations have very little evidence for immunosuppression. They might be effective but there’s no evidence yet [hence no recommendation in vascular manifestations].”
“Also, there’s no grade A evidence at all for musculoskeletal and gastrointestinal manifestations, and this should help to define the research agenda going forward,” Dr. Del Galdo said.
The 2023 recommendations task force comprised 28 members from 14 countries, including 18 rheumatologists, 1 EULAR methodologist, 1 health professional representative, 5 rheumatology fellows, 1 librarian, and 2 patient representatives. They used a consensual approach incorporating the views of 101 European Scleroderma Trials and Research group (EUSTAR) centers, sourced via a survey in which questions were advanced to an extensive systematic review if there was 70% or greater agreement.
Eventually, 31 questions on interventions were chosen, and the task force reviewed 12,500 abstracts (up to December 2022) related to interventions and outcomes that were either included in the 2017 recommendations or were totally new.
Dr. Del Galdo said that the three vascular manifestations of scleroderma – Raynaud’s, pulmonary arterial hypertension, and digital ulcers – were treated with the same drugs, all with a similar grade of evidence. “This suggests two things – firstly there’s a vascular disease continuum in the disease, and secondly, we’ve borrowed these drugs from vascular community, but we have not yet tested synthetic and biologic targeted treatments in these manifestations, and we should.
“Treating one manifestation may benefit the other, and this is important time wise because pulmonary hypertension usually comes around 10 years after the first phenomena so by treating digital ulcers and Raynaud’s phenomena, we may prevent pulmonary hypertension, but a study is needed,” added Dr. Del Galdo, who is also president of EUSTAR.
Finally, he pointed out that research remains particularly open for nonpharmacologic treatments for digital ulcers and severe gastrointestinal involvement. “Patients can now ask for studies into this because of the current lack of evidence.”
Moderator Ariane Herrick, PhD, professor of rheumatology at the University of Manchester (England), shared her thoughts on the guidelines. “These recommendations have been long awaited by the scleroderma community because there has been some exciting progress in recent years, and the new recommendations reflect these new developments.”
Commenting on the paucity of evidence in some areas, she added that “there do remain some huge areas of unmet need that are difficult to address, and these are musculoskeletal, gastrointestinal, and calcinosis, for which there have been no trials at all.”
Dr. Del Galdo declared disclosures relating to AstraZeneca, Janssen, Boehringer Ingelheim, Capella, Chemomab, GlaxoSmithKline, and Mitsubishi-Tanabe. Dr. Herrick disclosed serving as a consultant for Boehringer Ingelheim and Janssen.
MILAN – Targeted synthetic and biologic therapies are recommended as disease-modifying agents for key fibrotic manifestations of systemic sclerosis for the first time in the 2023 update of European Alliance of Associations for Rheumatology recommendations for the treatment of systemic sclerosis.
Reflecting important advances over the past 8 years, mostly relating to the use of new treatments being made available to patients, the recommendations provide an update on the 2017 recommendations, which relied on evidence published through 2014. Of note, these include the use of immunosuppressive agents, for example, the monoclonal antibody rituximab (Rituxan) for skin and lung fibrosis.
“For the first time, synthetic and targeted treatments are recommended for the treatment of systemic sclerosis–interstitial lung disease, including mycophenolate mofetil [Cellcept], nintedanib [Ofev], rituximab, and tocilizumab [Actemra]. None of these were present in 2017. Mycophenolate mofetil is also recommended for the treatment of skin fibrosis, and this was not present in 2017,” Francesco Del Galdo, MD, rheumatology consultant at Leeds Teaching Hospital NHS Trust, Leeds, England, and member of the 2023 recommendations task force, said in an interview. He gave an overview of the preliminary recommendations at the annual European Congress of Rheumatology.
“Phosphodiesterase-5 [PDE-5] inhibitors and endothelin receptor antagonist [ERA] monotherapy are also recommended for up-front combination use for digital ulcers and pulmonary hypertension, and this is new for 2023 and was not present in the 2017 recommendations,” Dr. Del Galdo added.
The new recommendations also note that iloprost is categorized as having grade A evidence for use in Raynaud’s phenomenon and digital ulcers, while it has grade B evidence for pulmonary hypertension.
“We are not allowed to share the final table [of recommendations] today because the wording has only very recently been agreed” upon, Dr. Del Galdo said, but he provided a summary representation and reflected on some changes, noting that the task force is aiming to publish the 2023 recommendations by the end of the year.
Consideration and discussion of both established and new evidence highlighted a need for more evidence on the use of immunosuppressive agents in vascular manifestations of systemic sclerosis, as well as for gastrointestinal and musculoskeletal ones.
In this update to the 2017 recommendations, high-grade evidence was identified for use of immunosuppressants in skin and lung fibrosis. Grade A evidence has been accepted for the use of rituximab in skin fibrosis; for interstitial lung disease, rituximab, cyclophosphamide, and nintedanib also have grade A evidence, which is a change from the 2017 recommendations.
A total of 20 updated recommendations were agreed on, an increase from 16 in 2017. These were grouped into eight disease domains: Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, skin fibrosis, interstitial lung disease, musculoskeletal and gastrointestinal manifestations, and renal crisis. Interventions were then graded A-D based on the evidence reviewed.
“This approach allowed us to see clearly that there were patterns of similar recommendations in different organ manifestations, reflecting an understanding of common pathogenic pathways,” said Dr. Del Galdo.
He also noted that the development of the recommendations highlighted certain gaps in research that limit treatment options. “By grouping the recommendations in blocks – for example, skin fibrosis or vascular [manifestations] – we show that immunosuppressive treatments have only been studied in skin and lung, while vascular manifestations have very little evidence for immunosuppression. They might be effective but there’s no evidence yet [hence no recommendation in vascular manifestations].”
“Also, there’s no grade A evidence at all for musculoskeletal and gastrointestinal manifestations, and this should help to define the research agenda going forward,” Dr. Del Galdo said.
The 2023 recommendations task force comprised 28 members from 14 countries, including 18 rheumatologists, 1 EULAR methodologist, 1 health professional representative, 5 rheumatology fellows, 1 librarian, and 2 patient representatives. They used a consensual approach incorporating the views of 101 European Scleroderma Trials and Research group (EUSTAR) centers, sourced via a survey in which questions were advanced to an extensive systematic review if there was 70% or greater agreement.
Eventually, 31 questions on interventions were chosen, and the task force reviewed 12,500 abstracts (up to December 2022) related to interventions and outcomes that were either included in the 2017 recommendations or were totally new.
Dr. Del Galdo said that the three vascular manifestations of scleroderma – Raynaud’s, pulmonary arterial hypertension, and digital ulcers – were treated with the same drugs, all with a similar grade of evidence. “This suggests two things – firstly there’s a vascular disease continuum in the disease, and secondly, we’ve borrowed these drugs from vascular community, but we have not yet tested synthetic and biologic targeted treatments in these manifestations, and we should.
“Treating one manifestation may benefit the other, and this is important time wise because pulmonary hypertension usually comes around 10 years after the first phenomena so by treating digital ulcers and Raynaud’s phenomena, we may prevent pulmonary hypertension, but a study is needed,” added Dr. Del Galdo, who is also president of EUSTAR.
Finally, he pointed out that research remains particularly open for nonpharmacologic treatments for digital ulcers and severe gastrointestinal involvement. “Patients can now ask for studies into this because of the current lack of evidence.”
Moderator Ariane Herrick, PhD, professor of rheumatology at the University of Manchester (England), shared her thoughts on the guidelines. “These recommendations have been long awaited by the scleroderma community because there has been some exciting progress in recent years, and the new recommendations reflect these new developments.”
Commenting on the paucity of evidence in some areas, she added that “there do remain some huge areas of unmet need that are difficult to address, and these are musculoskeletal, gastrointestinal, and calcinosis, for which there have been no trials at all.”
Dr. Del Galdo declared disclosures relating to AstraZeneca, Janssen, Boehringer Ingelheim, Capella, Chemomab, GlaxoSmithKline, and Mitsubishi-Tanabe. Dr. Herrick disclosed serving as a consultant for Boehringer Ingelheim and Janssen.
MILAN – Targeted synthetic and biologic therapies are recommended as disease-modifying agents for key fibrotic manifestations of systemic sclerosis for the first time in the 2023 update of European Alliance of Associations for Rheumatology recommendations for the treatment of systemic sclerosis.
Reflecting important advances over the past 8 years, mostly relating to the use of new treatments being made available to patients, the recommendations provide an update on the 2017 recommendations, which relied on evidence published through 2014. Of note, these include the use of immunosuppressive agents, for example, the monoclonal antibody rituximab (Rituxan) for skin and lung fibrosis.
“For the first time, synthetic and targeted treatments are recommended for the treatment of systemic sclerosis–interstitial lung disease, including mycophenolate mofetil [Cellcept], nintedanib [Ofev], rituximab, and tocilizumab [Actemra]. None of these were present in 2017. Mycophenolate mofetil is also recommended for the treatment of skin fibrosis, and this was not present in 2017,” Francesco Del Galdo, MD, rheumatology consultant at Leeds Teaching Hospital NHS Trust, Leeds, England, and member of the 2023 recommendations task force, said in an interview. He gave an overview of the preliminary recommendations at the annual European Congress of Rheumatology.
“Phosphodiesterase-5 [PDE-5] inhibitors and endothelin receptor antagonist [ERA] monotherapy are also recommended for up-front combination use for digital ulcers and pulmonary hypertension, and this is new for 2023 and was not present in the 2017 recommendations,” Dr. Del Galdo added.
The new recommendations also note that iloprost is categorized as having grade A evidence for use in Raynaud’s phenomenon and digital ulcers, while it has grade B evidence for pulmonary hypertension.
“We are not allowed to share the final table [of recommendations] today because the wording has only very recently been agreed” upon, Dr. Del Galdo said, but he provided a summary representation and reflected on some changes, noting that the task force is aiming to publish the 2023 recommendations by the end of the year.
Consideration and discussion of both established and new evidence highlighted a need for more evidence on the use of immunosuppressive agents in vascular manifestations of systemic sclerosis, as well as for gastrointestinal and musculoskeletal ones.
In this update to the 2017 recommendations, high-grade evidence was identified for use of immunosuppressants in skin and lung fibrosis. Grade A evidence has been accepted for the use of rituximab in skin fibrosis; for interstitial lung disease, rituximab, cyclophosphamide, and nintedanib also have grade A evidence, which is a change from the 2017 recommendations.
A total of 20 updated recommendations were agreed on, an increase from 16 in 2017. These were grouped into eight disease domains: Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, skin fibrosis, interstitial lung disease, musculoskeletal and gastrointestinal manifestations, and renal crisis. Interventions were then graded A-D based on the evidence reviewed.
“This approach allowed us to see clearly that there were patterns of similar recommendations in different organ manifestations, reflecting an understanding of common pathogenic pathways,” said Dr. Del Galdo.
He also noted that the development of the recommendations highlighted certain gaps in research that limit treatment options. “By grouping the recommendations in blocks – for example, skin fibrosis or vascular [manifestations] – we show that immunosuppressive treatments have only been studied in skin and lung, while vascular manifestations have very little evidence for immunosuppression. They might be effective but there’s no evidence yet [hence no recommendation in vascular manifestations].”
“Also, there’s no grade A evidence at all for musculoskeletal and gastrointestinal manifestations, and this should help to define the research agenda going forward,” Dr. Del Galdo said.
The 2023 recommendations task force comprised 28 members from 14 countries, including 18 rheumatologists, 1 EULAR methodologist, 1 health professional representative, 5 rheumatology fellows, 1 librarian, and 2 patient representatives. They used a consensual approach incorporating the views of 101 European Scleroderma Trials and Research group (EUSTAR) centers, sourced via a survey in which questions were advanced to an extensive systematic review if there was 70% or greater agreement.
Eventually, 31 questions on interventions were chosen, and the task force reviewed 12,500 abstracts (up to December 2022) related to interventions and outcomes that were either included in the 2017 recommendations or were totally new.
Dr. Del Galdo said that the three vascular manifestations of scleroderma – Raynaud’s, pulmonary arterial hypertension, and digital ulcers – were treated with the same drugs, all with a similar grade of evidence. “This suggests two things – firstly there’s a vascular disease continuum in the disease, and secondly, we’ve borrowed these drugs from vascular community, but we have not yet tested synthetic and biologic targeted treatments in these manifestations, and we should.
“Treating one manifestation may benefit the other, and this is important time wise because pulmonary hypertension usually comes around 10 years after the first phenomena so by treating digital ulcers and Raynaud’s phenomena, we may prevent pulmonary hypertension, but a study is needed,” added Dr. Del Galdo, who is also president of EUSTAR.
Finally, he pointed out that research remains particularly open for nonpharmacologic treatments for digital ulcers and severe gastrointestinal involvement. “Patients can now ask for studies into this because of the current lack of evidence.”
Moderator Ariane Herrick, PhD, professor of rheumatology at the University of Manchester (England), shared her thoughts on the guidelines. “These recommendations have been long awaited by the scleroderma community because there has been some exciting progress in recent years, and the new recommendations reflect these new developments.”
Commenting on the paucity of evidence in some areas, she added that “there do remain some huge areas of unmet need that are difficult to address, and these are musculoskeletal, gastrointestinal, and calcinosis, for which there have been no trials at all.”
Dr. Del Galdo declared disclosures relating to AstraZeneca, Janssen, Boehringer Ingelheim, Capella, Chemomab, GlaxoSmithKline, and Mitsubishi-Tanabe. Dr. Herrick disclosed serving as a consultant for Boehringer Ingelheim and Janssen.
AT EULAR 2023
SPF is only the start when recommending sunscreens
CHICAGO – at the inaugural Pigmentary Disorders Exchange Symposium.
Among the first factors physicians should consider before recommending sunscreen are a patient’s Fitzpatrick skin type, risks for burning or tanning, underlying skin disorders, and medications the patient is taking, Dr. Taylor, professor of dermatology at the University of Pennsylvania, Philadelphia, said at the meeting, provided by MedscapeLIVE! If patients are on hypertensives, for example, medications can make them more photosensitive.
Consider skin type
Dr. Taylor said she was dismayed by the results of a recent study, which found that 43% of dermatologists who responded to a survey reported that they never, rarely, or only sometimes took a patient’s skin type into account when making sunscreen recommendations. The article is referenced in a 2022 expert panel consensus paper she coauthored on photoprotection “for skin of all color.” But she pointed out that considering skin type alone is inadequate.
Questions for patients in joint decision-making should include lifestyle and work choices such as whether they work inside or outside, and how much sun exposure they get in a typical day. Heat and humidity levels should also be considered as should a patient’s susceptibility to dyspigmentation. “That could be overall darkening of the skin, mottled hyperpigmentation, actinic dyspigmentation, and, of course, propensity for skin cancer,” she said.
Use differs by race
Dr. Taylor, who is also vice chair for diversity, equity and inclusion in the department of dermatology at the University of Pennsylvania, pointed out that sunscreen use differs considerably by race.
In study of 8,952 adults in the United States who reported that they were sun sensitive found that a subset of adults with skin of color were significantly less likely to use sunscreen when compared with non-Hispanic White adults: Non-Hispanic Black (adjusted odds ratio, 0.43); non-Hispanic Asian (aOR. 0.54); and Hispanic (aOR, 0.70) adults.
In the study, non-Hispanic Black and Hispanic adults were significantly less likely to use sunscreens with an SPF greater than 15. In addition, non-Hispanic Black, non-Hispanic Asian, and Hispanic adults were significantly more likely than non-Hispanic Whites to wear long sleeves when outside. Such differences are important to keep in mind when advising patients about sunscreens, she said.
Protection for lighter-colored skin
Dr. Taylor said that, for patients with lighter skin tones, “we really want to protect against ultraviolet B as well as ultraviolet A, particularly ultraviolet A2. Ultraviolet radiation is going to cause DNA damage.” Patients with Fitzpatrick skin types I, II, or III are most susceptible to the effects of UVB with sunburn inflammation, which will cause erythema and tanning, and immunosuppression.
“For those who are I, II, and III, we do want to recommend a broad-spectrum, photostable sunscreen with a critical wavelength of 370 nanometers, which is going to protect from both UVB and UVA2,” she said.
Sunscreen recommendations are meant to be paired with advice to avoid midday sun from 10 a.m. to 2 p.m., wearing protective clothing and accessories, and seeking shade, she noted.
Dr. Taylor said, for those patients with lighter skin who are more susceptible to photodamage and premature aging, physicians should recommend sunscreens that contain DNA repair enzymes such as photolyases and sunscreens that contain antioxidants that can prevent or reverse DNA damage. “The exogenous form of these lyases have been manufactured and added to sunscreens,” Dr. Taylor said. “They’re readily available in the United States. That is something to consider for patients with significant photodamage.”
Retinoids can also help alleviate or reverse photodamage, she added.
Protection for darker-colored skin
“Many people of color do not believe they need sunscreen,” Dr. Taylor said. But studies show that, although there may be more intrinsic protection, sunscreen is still needed.
Over 30 years ago, Halder and colleagues reported that melanin in skin of color can filter two to five times more UV radiation, and in a paper on the photoprotective role of melanin, Kaidbey and colleagues found that skin types V and VI had an intrinsic SPF of 13 when compared with those who have lighter complexions, which had an SPF of 3.
Sunburns seem to occur less frequently in people with skin of color, but that may be because erythema is less apparent in people with darker skin tones or because of differences in personal definitions of sunburn, Dr. Taylor said.
“Skin of color can and does sustain sunburns and sunscreen will help prevent that,” she said, adding that a recommendation of an SPF 30 is likely sufficient for these patients. Dr. Taylor noted that sunscreens for patients with darker skin often cost substantially more than those for lighter skin, and that should be considered in recommendations.
Tinted sunscreens
Dr. Taylor said that, while broad-spectrum photostable sunscreens protect against UVB and UVA 2, they don’t protect from visible light and UVA1. Two methods to add that protection are using inorganic tinted sunscreens that contain iron oxide or pigmentary titanium dioxide. Dr. Taylor was a coauthor of a practical guide to tinted sunscreens published in 2022.
“For iron oxide, we want a concentration of 3% or greater,” she said, adding that the percentage often is not known because if it is contained in a sunscreen, it is listed as an inactive ingredient.
Another method to address visible light and UVA1 is the use of antioxidant-containing sunscreens with vitamin E, vitamin C, or licochalcone A, Dr. Taylor said.
During the question-and-answer period following her presentation, Amit Pandya, MD, adjunct professor of dermatology at University of Texas Southwestern Medical Center, Dallas, asked why “every makeup, every sunscreen, just says iron oxide,” since it is known that visible light will cause pigmentation, especially in those with darker skin tones.
He urged pushing for a law that would require listing the percentage of iron oxide on products to assure it is sufficient, according to what the literature recommends.
Conference Chair Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, said that she recommends tinted sunscreens almost exclusively for her patients, but those with darker skin colors struggle to match color.
Dr. Taylor referred to an analysis published in 2022 of 58 over-the counter sunscreens, which found that only 38% of tinted sunscreens was available in more than one shade, “which is a problem for many of our patients.” She said that providing samples with different hues and tactile sensations may help patients find the right product.
Dr. Taylor disclosed being on the advisory boards for AbbVie, Avita Medical, Beiersdorf, Biorez, Eli Lily, EPI Health, Evolus, Galderma, Hugel America, Johnson and Johnson, L’Oreal USA, MedScape, Pfizer, Scientis US, UCB, Vichy Laboratories. She is a consultant for Arcutis Biothermapeutics, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Dior, and Sanofi. She has done contracted research for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer, and has an ownership interest in Armis Scientific, GloGetter, and Piction Health.
Medscape and this news organization are owned by the same parent company.
CHICAGO – at the inaugural Pigmentary Disorders Exchange Symposium.
Among the first factors physicians should consider before recommending sunscreen are a patient’s Fitzpatrick skin type, risks for burning or tanning, underlying skin disorders, and medications the patient is taking, Dr. Taylor, professor of dermatology at the University of Pennsylvania, Philadelphia, said at the meeting, provided by MedscapeLIVE! If patients are on hypertensives, for example, medications can make them more photosensitive.
Consider skin type
Dr. Taylor said she was dismayed by the results of a recent study, which found that 43% of dermatologists who responded to a survey reported that they never, rarely, or only sometimes took a patient’s skin type into account when making sunscreen recommendations. The article is referenced in a 2022 expert panel consensus paper she coauthored on photoprotection “for skin of all color.” But she pointed out that considering skin type alone is inadequate.
Questions for patients in joint decision-making should include lifestyle and work choices such as whether they work inside or outside, and how much sun exposure they get in a typical day. Heat and humidity levels should also be considered as should a patient’s susceptibility to dyspigmentation. “That could be overall darkening of the skin, mottled hyperpigmentation, actinic dyspigmentation, and, of course, propensity for skin cancer,” she said.
Use differs by race
Dr. Taylor, who is also vice chair for diversity, equity and inclusion in the department of dermatology at the University of Pennsylvania, pointed out that sunscreen use differs considerably by race.
In study of 8,952 adults in the United States who reported that they were sun sensitive found that a subset of adults with skin of color were significantly less likely to use sunscreen when compared with non-Hispanic White adults: Non-Hispanic Black (adjusted odds ratio, 0.43); non-Hispanic Asian (aOR. 0.54); and Hispanic (aOR, 0.70) adults.
In the study, non-Hispanic Black and Hispanic adults were significantly less likely to use sunscreens with an SPF greater than 15. In addition, non-Hispanic Black, non-Hispanic Asian, and Hispanic adults were significantly more likely than non-Hispanic Whites to wear long sleeves when outside. Such differences are important to keep in mind when advising patients about sunscreens, she said.
Protection for lighter-colored skin
Dr. Taylor said that, for patients with lighter skin tones, “we really want to protect against ultraviolet B as well as ultraviolet A, particularly ultraviolet A2. Ultraviolet radiation is going to cause DNA damage.” Patients with Fitzpatrick skin types I, II, or III are most susceptible to the effects of UVB with sunburn inflammation, which will cause erythema and tanning, and immunosuppression.
“For those who are I, II, and III, we do want to recommend a broad-spectrum, photostable sunscreen with a critical wavelength of 370 nanometers, which is going to protect from both UVB and UVA2,” she said.
Sunscreen recommendations are meant to be paired with advice to avoid midday sun from 10 a.m. to 2 p.m., wearing protective clothing and accessories, and seeking shade, she noted.
Dr. Taylor said, for those patients with lighter skin who are more susceptible to photodamage and premature aging, physicians should recommend sunscreens that contain DNA repair enzymes such as photolyases and sunscreens that contain antioxidants that can prevent or reverse DNA damage. “The exogenous form of these lyases have been manufactured and added to sunscreens,” Dr. Taylor said. “They’re readily available in the United States. That is something to consider for patients with significant photodamage.”
Retinoids can also help alleviate or reverse photodamage, she added.
Protection for darker-colored skin
“Many people of color do not believe they need sunscreen,” Dr. Taylor said. But studies show that, although there may be more intrinsic protection, sunscreen is still needed.
Over 30 years ago, Halder and colleagues reported that melanin in skin of color can filter two to five times more UV radiation, and in a paper on the photoprotective role of melanin, Kaidbey and colleagues found that skin types V and VI had an intrinsic SPF of 13 when compared with those who have lighter complexions, which had an SPF of 3.
Sunburns seem to occur less frequently in people with skin of color, but that may be because erythema is less apparent in people with darker skin tones or because of differences in personal definitions of sunburn, Dr. Taylor said.
“Skin of color can and does sustain sunburns and sunscreen will help prevent that,” she said, adding that a recommendation of an SPF 30 is likely sufficient for these patients. Dr. Taylor noted that sunscreens for patients with darker skin often cost substantially more than those for lighter skin, and that should be considered in recommendations.
Tinted sunscreens
Dr. Taylor said that, while broad-spectrum photostable sunscreens protect against UVB and UVA 2, they don’t protect from visible light and UVA1. Two methods to add that protection are using inorganic tinted sunscreens that contain iron oxide or pigmentary titanium dioxide. Dr. Taylor was a coauthor of a practical guide to tinted sunscreens published in 2022.
“For iron oxide, we want a concentration of 3% or greater,” she said, adding that the percentage often is not known because if it is contained in a sunscreen, it is listed as an inactive ingredient.
Another method to address visible light and UVA1 is the use of antioxidant-containing sunscreens with vitamin E, vitamin C, or licochalcone A, Dr. Taylor said.
During the question-and-answer period following her presentation, Amit Pandya, MD, adjunct professor of dermatology at University of Texas Southwestern Medical Center, Dallas, asked why “every makeup, every sunscreen, just says iron oxide,” since it is known that visible light will cause pigmentation, especially in those with darker skin tones.
He urged pushing for a law that would require listing the percentage of iron oxide on products to assure it is sufficient, according to what the literature recommends.
Conference Chair Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, said that she recommends tinted sunscreens almost exclusively for her patients, but those with darker skin colors struggle to match color.
Dr. Taylor referred to an analysis published in 2022 of 58 over-the counter sunscreens, which found that only 38% of tinted sunscreens was available in more than one shade, “which is a problem for many of our patients.” She said that providing samples with different hues and tactile sensations may help patients find the right product.
Dr. Taylor disclosed being on the advisory boards for AbbVie, Avita Medical, Beiersdorf, Biorez, Eli Lily, EPI Health, Evolus, Galderma, Hugel America, Johnson and Johnson, L’Oreal USA, MedScape, Pfizer, Scientis US, UCB, Vichy Laboratories. She is a consultant for Arcutis Biothermapeutics, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Dior, and Sanofi. She has done contracted research for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer, and has an ownership interest in Armis Scientific, GloGetter, and Piction Health.
Medscape and this news organization are owned by the same parent company.
CHICAGO – at the inaugural Pigmentary Disorders Exchange Symposium.
Among the first factors physicians should consider before recommending sunscreen are a patient’s Fitzpatrick skin type, risks for burning or tanning, underlying skin disorders, and medications the patient is taking, Dr. Taylor, professor of dermatology at the University of Pennsylvania, Philadelphia, said at the meeting, provided by MedscapeLIVE! If patients are on hypertensives, for example, medications can make them more photosensitive.
Consider skin type
Dr. Taylor said she was dismayed by the results of a recent study, which found that 43% of dermatologists who responded to a survey reported that they never, rarely, or only sometimes took a patient’s skin type into account when making sunscreen recommendations. The article is referenced in a 2022 expert panel consensus paper she coauthored on photoprotection “for skin of all color.” But she pointed out that considering skin type alone is inadequate.
Questions for patients in joint decision-making should include lifestyle and work choices such as whether they work inside or outside, and how much sun exposure they get in a typical day. Heat and humidity levels should also be considered as should a patient’s susceptibility to dyspigmentation. “That could be overall darkening of the skin, mottled hyperpigmentation, actinic dyspigmentation, and, of course, propensity for skin cancer,” she said.
Use differs by race
Dr. Taylor, who is also vice chair for diversity, equity and inclusion in the department of dermatology at the University of Pennsylvania, pointed out that sunscreen use differs considerably by race.
In study of 8,952 adults in the United States who reported that they were sun sensitive found that a subset of adults with skin of color were significantly less likely to use sunscreen when compared with non-Hispanic White adults: Non-Hispanic Black (adjusted odds ratio, 0.43); non-Hispanic Asian (aOR. 0.54); and Hispanic (aOR, 0.70) adults.
In the study, non-Hispanic Black and Hispanic adults were significantly less likely to use sunscreens with an SPF greater than 15. In addition, non-Hispanic Black, non-Hispanic Asian, and Hispanic adults were significantly more likely than non-Hispanic Whites to wear long sleeves when outside. Such differences are important to keep in mind when advising patients about sunscreens, she said.
Protection for lighter-colored skin
Dr. Taylor said that, for patients with lighter skin tones, “we really want to protect against ultraviolet B as well as ultraviolet A, particularly ultraviolet A2. Ultraviolet radiation is going to cause DNA damage.” Patients with Fitzpatrick skin types I, II, or III are most susceptible to the effects of UVB with sunburn inflammation, which will cause erythema and tanning, and immunosuppression.
“For those who are I, II, and III, we do want to recommend a broad-spectrum, photostable sunscreen with a critical wavelength of 370 nanometers, which is going to protect from both UVB and UVA2,” she said.
Sunscreen recommendations are meant to be paired with advice to avoid midday sun from 10 a.m. to 2 p.m., wearing protective clothing and accessories, and seeking shade, she noted.
Dr. Taylor said, for those patients with lighter skin who are more susceptible to photodamage and premature aging, physicians should recommend sunscreens that contain DNA repair enzymes such as photolyases and sunscreens that contain antioxidants that can prevent or reverse DNA damage. “The exogenous form of these lyases have been manufactured and added to sunscreens,” Dr. Taylor said. “They’re readily available in the United States. That is something to consider for patients with significant photodamage.”
Retinoids can also help alleviate or reverse photodamage, she added.
Protection for darker-colored skin
“Many people of color do not believe they need sunscreen,” Dr. Taylor said. But studies show that, although there may be more intrinsic protection, sunscreen is still needed.
Over 30 years ago, Halder and colleagues reported that melanin in skin of color can filter two to five times more UV radiation, and in a paper on the photoprotective role of melanin, Kaidbey and colleagues found that skin types V and VI had an intrinsic SPF of 13 when compared with those who have lighter complexions, which had an SPF of 3.
Sunburns seem to occur less frequently in people with skin of color, but that may be because erythema is less apparent in people with darker skin tones or because of differences in personal definitions of sunburn, Dr. Taylor said.
“Skin of color can and does sustain sunburns and sunscreen will help prevent that,” she said, adding that a recommendation of an SPF 30 is likely sufficient for these patients. Dr. Taylor noted that sunscreens for patients with darker skin often cost substantially more than those for lighter skin, and that should be considered in recommendations.
Tinted sunscreens
Dr. Taylor said that, while broad-spectrum photostable sunscreens protect against UVB and UVA 2, they don’t protect from visible light and UVA1. Two methods to add that protection are using inorganic tinted sunscreens that contain iron oxide or pigmentary titanium dioxide. Dr. Taylor was a coauthor of a practical guide to tinted sunscreens published in 2022.
“For iron oxide, we want a concentration of 3% or greater,” she said, adding that the percentage often is not known because if it is contained in a sunscreen, it is listed as an inactive ingredient.
Another method to address visible light and UVA1 is the use of antioxidant-containing sunscreens with vitamin E, vitamin C, or licochalcone A, Dr. Taylor said.
During the question-and-answer period following her presentation, Amit Pandya, MD, adjunct professor of dermatology at University of Texas Southwestern Medical Center, Dallas, asked why “every makeup, every sunscreen, just says iron oxide,” since it is known that visible light will cause pigmentation, especially in those with darker skin tones.
He urged pushing for a law that would require listing the percentage of iron oxide on products to assure it is sufficient, according to what the literature recommends.
Conference Chair Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, said that she recommends tinted sunscreens almost exclusively for her patients, but those with darker skin colors struggle to match color.
Dr. Taylor referred to an analysis published in 2022 of 58 over-the counter sunscreens, which found that only 38% of tinted sunscreens was available in more than one shade, “which is a problem for many of our patients.” She said that providing samples with different hues and tactile sensations may help patients find the right product.
Dr. Taylor disclosed being on the advisory boards for AbbVie, Avita Medical, Beiersdorf, Biorez, Eli Lily, EPI Health, Evolus, Galderma, Hugel America, Johnson and Johnson, L’Oreal USA, MedScape, Pfizer, Scientis US, UCB, Vichy Laboratories. She is a consultant for Arcutis Biothermapeutics, Beiersdorf, Bristol-Myers Squibb, Cara Therapeutics, Dior, and Sanofi. She has done contracted research for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer, and has an ownership interest in Armis Scientific, GloGetter, and Piction Health.
Medscape and this news organization are owned by the same parent company.
AT THE MEDSCAPELIVE! PIGMENTARY DISORDERS SYMPOSIUM
Scientists discover variants, therapy for disabling pansclerotic morphea
A team of especially in patients who have not responded to other interventions.
DPM was first reported in 1923, and while a genetic cause has been suspected, it had not been identified until now. The disease is the most severe form of deep morphea, which affects individuals with juvenile localized scleroderma. Patients, generally children under age 14, experience rapid sclerosis of all layers of the skin, fascia, muscle, and bone. DPM is also deadly: Most patients do not live more than 10 years after diagnosis, as they contract squamous cell carcinoma, restrictive pulmonary disease, sepsis, and gangrene.
In the study, published in the New England Journal of Medicine, the researchers discovered that people with DPM have an overactive version of the protein STAT4, which regulates inflammation and wound healing. The scientists studied four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM.
“Researchers previously thought that this disorder was caused by the immune system attacking the skin,” Sarah Blackstone, a predoctoral fellow in the inflammatory disease section at the National Human Genome Research Institute and co–first author of the study, said in a statement from the National Institutes of Health describing the results. “However, we found that this is an oversimplification, and that both skin and the immune system play an active role in disabling pansclerotic morphea,” added Ms. Blackstone, also a medical student at the University of South Dakota, Sioux Falls.
The overactive STAT4 protein creates a positive feedback loop of inflammation and impaired wound-healing. By targeting JAK, the researchers were able to stop the feedback and patients’ wounds dramatically improved. After 18 months of treatment with oral ruxolitinib, one patient had discontinued all other medications, and had complete resolution of a chest rash, substantial clearing on the arms and legs, and global clinical improvement.
The authors said that oral systemic JAK inhibitor therapy is preferred over topical therapy. Their research also suggested that anti–interleukin-6 monoclonal antibodies – such as tocilizumab, approved for indications that include rheumatoid arthritis and systemic sclerosis–associated interstitial lung disease, “may be an alternative therapy or may be useful in combination with JAK inhibitors in patients with DPM,” the authors wrote.
Most current DPM therapies – including methotrexate, mycophenolate mofetil, and ultraviolet A light therapy – have been ineffective, and some have severe side effects.
“The findings of this study open doors for JAK inhibitors to be a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, whether it is scarring of the lungs, liver or bone marrow,” Dan Kastner, MD, PhD, an NIH distinguished investigator, head of the NHGRI’s inflammatory disease section, and a senior author of the paper, said in the NIH statement.
“We hope to continue studying other molecules in this pathway and how they are altered in patients with disabling pansclerotic morphea and related conditions to find clues to understanding a broader array of more common diseases,” Lori Broderick, MD, PhD, a senior author of the paper and an associate professor at University of California, San Diego, said in the statement.
The study was led by researchers at NHGRI in collaboration with researchers from UCSD and the University of Pittsburgh. Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases also participated.
The study was supported by grants from the American Academy of Allergy, Asthma, and Immunology Foundation; the Ludwig Institute for Cancer Research; the University of California, San Diego, department of pediatrics; and the Novo Nordisk Foundation. Additional support and grants were given by the Deutsche Forschungsgemeinschaft, various institutes at the NIH, the California Institute for Regenerative Medicine, the Hydrocephalus Association, the Scleroderma Research Foundation, the Biowulf High-Performance Computing Cluster of the Center for Information Technology, the Undiagnosed Diseases Program of the Common Fund of the Office of the Director of the NIH, and the NIH Clinical Center.
A team of especially in patients who have not responded to other interventions.
DPM was first reported in 1923, and while a genetic cause has been suspected, it had not been identified until now. The disease is the most severe form of deep morphea, which affects individuals with juvenile localized scleroderma. Patients, generally children under age 14, experience rapid sclerosis of all layers of the skin, fascia, muscle, and bone. DPM is also deadly: Most patients do not live more than 10 years after diagnosis, as they contract squamous cell carcinoma, restrictive pulmonary disease, sepsis, and gangrene.
In the study, published in the New England Journal of Medicine, the researchers discovered that people with DPM have an overactive version of the protein STAT4, which regulates inflammation and wound healing. The scientists studied four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM.
“Researchers previously thought that this disorder was caused by the immune system attacking the skin,” Sarah Blackstone, a predoctoral fellow in the inflammatory disease section at the National Human Genome Research Institute and co–first author of the study, said in a statement from the National Institutes of Health describing the results. “However, we found that this is an oversimplification, and that both skin and the immune system play an active role in disabling pansclerotic morphea,” added Ms. Blackstone, also a medical student at the University of South Dakota, Sioux Falls.
The overactive STAT4 protein creates a positive feedback loop of inflammation and impaired wound-healing. By targeting JAK, the researchers were able to stop the feedback and patients’ wounds dramatically improved. After 18 months of treatment with oral ruxolitinib, one patient had discontinued all other medications, and had complete resolution of a chest rash, substantial clearing on the arms and legs, and global clinical improvement.
The authors said that oral systemic JAK inhibitor therapy is preferred over topical therapy. Their research also suggested that anti–interleukin-6 monoclonal antibodies – such as tocilizumab, approved for indications that include rheumatoid arthritis and systemic sclerosis–associated interstitial lung disease, “may be an alternative therapy or may be useful in combination with JAK inhibitors in patients with DPM,” the authors wrote.
Most current DPM therapies – including methotrexate, mycophenolate mofetil, and ultraviolet A light therapy – have been ineffective, and some have severe side effects.
“The findings of this study open doors for JAK inhibitors to be a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, whether it is scarring of the lungs, liver or bone marrow,” Dan Kastner, MD, PhD, an NIH distinguished investigator, head of the NHGRI’s inflammatory disease section, and a senior author of the paper, said in the NIH statement.
“We hope to continue studying other molecules in this pathway and how they are altered in patients with disabling pansclerotic morphea and related conditions to find clues to understanding a broader array of more common diseases,” Lori Broderick, MD, PhD, a senior author of the paper and an associate professor at University of California, San Diego, said in the statement.
The study was led by researchers at NHGRI in collaboration with researchers from UCSD and the University of Pittsburgh. Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases also participated.
The study was supported by grants from the American Academy of Allergy, Asthma, and Immunology Foundation; the Ludwig Institute for Cancer Research; the University of California, San Diego, department of pediatrics; and the Novo Nordisk Foundation. Additional support and grants were given by the Deutsche Forschungsgemeinschaft, various institutes at the NIH, the California Institute for Regenerative Medicine, the Hydrocephalus Association, the Scleroderma Research Foundation, the Biowulf High-Performance Computing Cluster of the Center for Information Technology, the Undiagnosed Diseases Program of the Common Fund of the Office of the Director of the NIH, and the NIH Clinical Center.
A team of especially in patients who have not responded to other interventions.
DPM was first reported in 1923, and while a genetic cause has been suspected, it had not been identified until now. The disease is the most severe form of deep morphea, which affects individuals with juvenile localized scleroderma. Patients, generally children under age 14, experience rapid sclerosis of all layers of the skin, fascia, muscle, and bone. DPM is also deadly: Most patients do not live more than 10 years after diagnosis, as they contract squamous cell carcinoma, restrictive pulmonary disease, sepsis, and gangrene.
In the study, published in the New England Journal of Medicine, the researchers discovered that people with DPM have an overactive version of the protein STAT4, which regulates inflammation and wound healing. The scientists studied four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM.
“Researchers previously thought that this disorder was caused by the immune system attacking the skin,” Sarah Blackstone, a predoctoral fellow in the inflammatory disease section at the National Human Genome Research Institute and co–first author of the study, said in a statement from the National Institutes of Health describing the results. “However, we found that this is an oversimplification, and that both skin and the immune system play an active role in disabling pansclerotic morphea,” added Ms. Blackstone, also a medical student at the University of South Dakota, Sioux Falls.
The overactive STAT4 protein creates a positive feedback loop of inflammation and impaired wound-healing. By targeting JAK, the researchers were able to stop the feedback and patients’ wounds dramatically improved. After 18 months of treatment with oral ruxolitinib, one patient had discontinued all other medications, and had complete resolution of a chest rash, substantial clearing on the arms and legs, and global clinical improvement.
The authors said that oral systemic JAK inhibitor therapy is preferred over topical therapy. Their research also suggested that anti–interleukin-6 monoclonal antibodies – such as tocilizumab, approved for indications that include rheumatoid arthritis and systemic sclerosis–associated interstitial lung disease, “may be an alternative therapy or may be useful in combination with JAK inhibitors in patients with DPM,” the authors wrote.
Most current DPM therapies – including methotrexate, mycophenolate mofetil, and ultraviolet A light therapy – have been ineffective, and some have severe side effects.
“The findings of this study open doors for JAK inhibitors to be a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, whether it is scarring of the lungs, liver or bone marrow,” Dan Kastner, MD, PhD, an NIH distinguished investigator, head of the NHGRI’s inflammatory disease section, and a senior author of the paper, said in the NIH statement.
“We hope to continue studying other molecules in this pathway and how they are altered in patients with disabling pansclerotic morphea and related conditions to find clues to understanding a broader array of more common diseases,” Lori Broderick, MD, PhD, a senior author of the paper and an associate professor at University of California, San Diego, said in the statement.
The study was led by researchers at NHGRI in collaboration with researchers from UCSD and the University of Pittsburgh. Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases also participated.
The study was supported by grants from the American Academy of Allergy, Asthma, and Immunology Foundation; the Ludwig Institute for Cancer Research; the University of California, San Diego, department of pediatrics; and the Novo Nordisk Foundation. Additional support and grants were given by the Deutsche Forschungsgemeinschaft, various institutes at the NIH, the California Institute for Regenerative Medicine, the Hydrocephalus Association, the Scleroderma Research Foundation, the Biowulf High-Performance Computing Cluster of the Center for Information Technology, the Undiagnosed Diseases Program of the Common Fund of the Office of the Director of the NIH, and the NIH Clinical Center.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE