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Novel hydrogel holds promise for skin regeneration
CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.
But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the .
“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”
Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”
Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”
Approaches to skin regeneration
Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”
Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”
Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”
The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.
During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”
In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.
Clinical trials planned
The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.
Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.
CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.
But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the .
“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”
Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”
Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”
Approaches to skin regeneration
Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”
Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”
Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”
The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.
During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”
In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.
Clinical trials planned
The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.
Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.
CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.
But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the .
“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”
Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”
Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”
Approaches to skin regeneration
Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”
Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”
Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”
The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.
During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”
In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.
Clinical trials planned
The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.
Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.
AT CALDERM 2023
Multicenter study aims to find new treatments for hidradenitis suppurativa
When Haley Naik, MD, joined the University of California, San Francisco, as a dermatologist in 2015, she was struck by the dearth of data in the medical literature about hidradenitis suppurativa (HS).
“For decades there were no datasets to begin to understand HS – its clinical course, how patients respond to medications, and how quality of life improves for patients with therapy,” Dr. Naik, who directs the HS program at UCSF, said in an interview. Inspired to improve the bleak HS knowledge landscape, she began to systematically collect information from HS patient visits, “to try to better understand how treatments were helping them or not and also to better understand their quality-of-life impact,” she said. “This also facilitated research in HS, but over time it became clear that there was a growing need for a larger effort.”
But in 2020, Dr. Naik teamed up with investigative dermatologist Michelle Lowes, MBBS, PhD, to . To date, more than 500 patients are enrolled at 12 participating sites, and 4 more sites plan to join the consortium by the end of 2023. The goal is to enroll a total of 8,000 patients, which will make it the largest dataset of its kind.
“Each site investigator is a physician who specializes in taking care of HS patients,” said Dr. Naik, who is the study’s principal investigator. “These are people who are conducting active research in various aspects of HS, and they’re trusted members of the medical community.”
She highlighted the three main objectives of HS PROGRESS. The first objective is to develop a longitudinal cohort of HS patients so that investigators can understand the clinical course of HS and effectiveness of treatments. The second is to collect biospecimens from patients with HS for translational studies “that can help to drive drug development, help us identify biomarkers that can help us predict disease course and predict patient response to therapies, so we know exactly what to give them,” she explained. The third objective is to provide patients with HS with the opportunity to be recruited for clinical trials, “so they have access to cutting-edge therapies and know what’s happening in this space.”
Collecting biospecimens
The goal of collecting biospecimens is to provide them to multiple investigators to improve the understanding of HS biology and treatment. “Our thought is to apply next generation techniques to these biospecimens to get metagenomic, transcriptomic, and genomic data to better understand HS biology so that we can identify targets for novel therapy,” Dr. Naik said.
Although HS is estimated to affect 1% of Western populations, the tumor necrosis alpha (TNF)-inhibitor adalimumab remains the only Food and Drug Administration-approved therapy for the condition.
However, Dr. Naik said that there are many promising drugs on the horizon for HS, especially interleukin (IL)-17 inhibitors. “One of the most exciting things about these drugs is that they set the bar higher for what we can expect out of therapies for HS, such as reporting a HiSCR (HS Clinical Response) score 75, which is the equivalent of 75% improvement in inflammatory HS lesions without an increase in draining tunnels,” she said. “This is well beyond what adalimumab had demonstrated in landmark trials in 2015. The safety profile on IL-17 inhibitors looks great, too.”
JAK inhibitors also hold promise for HS. “It’s going to be key to see how these drugs perform in the real-world setting in our average HS patients who may have comorbidities,” Dr. Naik said. “This is where an effort like HS PROGRESS will carry weight, because in a dataset like this, we’re going to be able to ask questions like, is there a class of drugs that works better for one specific phenotype of HS, or for patients who have a younger age of onset, or who are earlier in their disease course? These are questions we can’t ask in the context of a clinical trial, but we can ask in the context of real-world data from many practices.”
In addition to USCF, the 11 study locations participating in HS PROGRESS are the University of North Carolina at Chapel Hill; Mayo Clinic; Penn State University, Hershey; University of Virginia, Charlottesville; Washington University in St. Louis; University of Southern California, Los Angeles; Henry Ford Health, Detroit; University of Minnesota; University of Pennsylvania, Philadelphia; Duke University, Durham, N.C.; and University of Miami.
Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, UCB, and Novartis; and investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.
When Haley Naik, MD, joined the University of California, San Francisco, as a dermatologist in 2015, she was struck by the dearth of data in the medical literature about hidradenitis suppurativa (HS).
“For decades there were no datasets to begin to understand HS – its clinical course, how patients respond to medications, and how quality of life improves for patients with therapy,” Dr. Naik, who directs the HS program at UCSF, said in an interview. Inspired to improve the bleak HS knowledge landscape, she began to systematically collect information from HS patient visits, “to try to better understand how treatments were helping them or not and also to better understand their quality-of-life impact,” she said. “This also facilitated research in HS, but over time it became clear that there was a growing need for a larger effort.”
But in 2020, Dr. Naik teamed up with investigative dermatologist Michelle Lowes, MBBS, PhD, to . To date, more than 500 patients are enrolled at 12 participating sites, and 4 more sites plan to join the consortium by the end of 2023. The goal is to enroll a total of 8,000 patients, which will make it the largest dataset of its kind.
“Each site investigator is a physician who specializes in taking care of HS patients,” said Dr. Naik, who is the study’s principal investigator. “These are people who are conducting active research in various aspects of HS, and they’re trusted members of the medical community.”
She highlighted the three main objectives of HS PROGRESS. The first objective is to develop a longitudinal cohort of HS patients so that investigators can understand the clinical course of HS and effectiveness of treatments. The second is to collect biospecimens from patients with HS for translational studies “that can help to drive drug development, help us identify biomarkers that can help us predict disease course and predict patient response to therapies, so we know exactly what to give them,” she explained. The third objective is to provide patients with HS with the opportunity to be recruited for clinical trials, “so they have access to cutting-edge therapies and know what’s happening in this space.”
Collecting biospecimens
The goal of collecting biospecimens is to provide them to multiple investigators to improve the understanding of HS biology and treatment. “Our thought is to apply next generation techniques to these biospecimens to get metagenomic, transcriptomic, and genomic data to better understand HS biology so that we can identify targets for novel therapy,” Dr. Naik said.
Although HS is estimated to affect 1% of Western populations, the tumor necrosis alpha (TNF)-inhibitor adalimumab remains the only Food and Drug Administration-approved therapy for the condition.
However, Dr. Naik said that there are many promising drugs on the horizon for HS, especially interleukin (IL)-17 inhibitors. “One of the most exciting things about these drugs is that they set the bar higher for what we can expect out of therapies for HS, such as reporting a HiSCR (HS Clinical Response) score 75, which is the equivalent of 75% improvement in inflammatory HS lesions without an increase in draining tunnels,” she said. “This is well beyond what adalimumab had demonstrated in landmark trials in 2015. The safety profile on IL-17 inhibitors looks great, too.”
JAK inhibitors also hold promise for HS. “It’s going to be key to see how these drugs perform in the real-world setting in our average HS patients who may have comorbidities,” Dr. Naik said. “This is where an effort like HS PROGRESS will carry weight, because in a dataset like this, we’re going to be able to ask questions like, is there a class of drugs that works better for one specific phenotype of HS, or for patients who have a younger age of onset, or who are earlier in their disease course? These are questions we can’t ask in the context of a clinical trial, but we can ask in the context of real-world data from many practices.”
In addition to USCF, the 11 study locations participating in HS PROGRESS are the University of North Carolina at Chapel Hill; Mayo Clinic; Penn State University, Hershey; University of Virginia, Charlottesville; Washington University in St. Louis; University of Southern California, Los Angeles; Henry Ford Health, Detroit; University of Minnesota; University of Pennsylvania, Philadelphia; Duke University, Durham, N.C.; and University of Miami.
Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, UCB, and Novartis; and investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.
When Haley Naik, MD, joined the University of California, San Francisco, as a dermatologist in 2015, she was struck by the dearth of data in the medical literature about hidradenitis suppurativa (HS).
“For decades there were no datasets to begin to understand HS – its clinical course, how patients respond to medications, and how quality of life improves for patients with therapy,” Dr. Naik, who directs the HS program at UCSF, said in an interview. Inspired to improve the bleak HS knowledge landscape, she began to systematically collect information from HS patient visits, “to try to better understand how treatments were helping them or not and also to better understand their quality-of-life impact,” she said. “This also facilitated research in HS, but over time it became clear that there was a growing need for a larger effort.”
But in 2020, Dr. Naik teamed up with investigative dermatologist Michelle Lowes, MBBS, PhD, to . To date, more than 500 patients are enrolled at 12 participating sites, and 4 more sites plan to join the consortium by the end of 2023. The goal is to enroll a total of 8,000 patients, which will make it the largest dataset of its kind.
“Each site investigator is a physician who specializes in taking care of HS patients,” said Dr. Naik, who is the study’s principal investigator. “These are people who are conducting active research in various aspects of HS, and they’re trusted members of the medical community.”
She highlighted the three main objectives of HS PROGRESS. The first objective is to develop a longitudinal cohort of HS patients so that investigators can understand the clinical course of HS and effectiveness of treatments. The second is to collect biospecimens from patients with HS for translational studies “that can help to drive drug development, help us identify biomarkers that can help us predict disease course and predict patient response to therapies, so we know exactly what to give them,” she explained. The third objective is to provide patients with HS with the opportunity to be recruited for clinical trials, “so they have access to cutting-edge therapies and know what’s happening in this space.”
Collecting biospecimens
The goal of collecting biospecimens is to provide them to multiple investigators to improve the understanding of HS biology and treatment. “Our thought is to apply next generation techniques to these biospecimens to get metagenomic, transcriptomic, and genomic data to better understand HS biology so that we can identify targets for novel therapy,” Dr. Naik said.
Although HS is estimated to affect 1% of Western populations, the tumor necrosis alpha (TNF)-inhibitor adalimumab remains the only Food and Drug Administration-approved therapy for the condition.
However, Dr. Naik said that there are many promising drugs on the horizon for HS, especially interleukin (IL)-17 inhibitors. “One of the most exciting things about these drugs is that they set the bar higher for what we can expect out of therapies for HS, such as reporting a HiSCR (HS Clinical Response) score 75, which is the equivalent of 75% improvement in inflammatory HS lesions without an increase in draining tunnels,” she said. “This is well beyond what adalimumab had demonstrated in landmark trials in 2015. The safety profile on IL-17 inhibitors looks great, too.”
JAK inhibitors also hold promise for HS. “It’s going to be key to see how these drugs perform in the real-world setting in our average HS patients who may have comorbidities,” Dr. Naik said. “This is where an effort like HS PROGRESS will carry weight, because in a dataset like this, we’re going to be able to ask questions like, is there a class of drugs that works better for one specific phenotype of HS, or for patients who have a younger age of onset, or who are earlier in their disease course? These are questions we can’t ask in the context of a clinical trial, but we can ask in the context of real-world data from many practices.”
In addition to USCF, the 11 study locations participating in HS PROGRESS are the University of North Carolina at Chapel Hill; Mayo Clinic; Penn State University, Hershey; University of Virginia, Charlottesville; Washington University in St. Louis; University of Southern California, Los Angeles; Henry Ford Health, Detroit; University of Minnesota; University of Pennsylvania, Philadelphia; Duke University, Durham, N.C.; and University of Miami.
Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, UCB, and Novartis; and investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.
Systematic review spotlights the use of nutraceuticals for acne
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“While many topical and systemic prescription options are available for the treatment of acne, some patients may be interested in natural and complementary therapies as either an adjunctive or an alternative to prescription medications,” researchers led by John S. Barbieri, MD, MBA, of the department of dermatology at Brigham and Women’s Hospital, Boston, wrote in their study, which was published online in JAMA Dermatology. The researchers defined nutraceuticals as products derived from food sources that provide both nutritional and medicinal benefits, such as vitamins, dietary supplements, and herbal products. “Although patients may be interested in nutraceuticals as a potential treatment option for acne, there is uncertainty regarding the efficacy and safety of these products,” they wrote.
For the systematic review, they searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception through January 30, 2023, to identify randomized clinical trials that evaluated oral nutraceutical interventions such as vitamins and minerals, botanical extracts, prebiotics, and probiotics in individuals with acne. They extracted clinician-reported outcomes, patient-reported outcomes, and adverse events from the included studies, and used the Cochrane Risk of Bias checklist tool to assess the quality of evidence in randomized clinical trials. Based on this tool, they used Agency for Healthcare Research and Quality standards to categorize the articles as good, fair, or poor quality.
The search yielded 42 unique studies with 3,346 participants. Of these 42 studies, 27 were considered poor quality, 11 were considered fair quality, and 4 were considered good quality. The good-quality studies separately evaluated four interventions: vitamin D, green tea extract, probiotics, and cheongsangbangpoong-tang, an herbal formula approved for use in acne by the Korea Food and Drug Administration.
The 11 fair-quality studies suggested potential effectiveness for pantothenic acid (vitamin B5), the fatty acids omega-3 (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) and omega-6 (gamma-linoleic acid), and probiotics.
Zinc was the most studied nutraceutical identified in the review, but “there was substantial heterogeneity in the results, with only slightly greater than one-half of studies finding zinc to be efficacious,” the authors noted. “Studies using higher doses more often found zinc to be efficacious,” they said, adding that zinc “had the highest rate of adverse effect reporting of any nutraceuticals assessed in this review.”
Dr. Barbieri and colleagues acknowledged limitations of their analysis, including the fact that few of the nutraceuticals considered to have good or fair evidence for their use were evaluated in more than one study. “In addition, some studies had inconsistent results depending on the outcome measure assessed,” they wrote. “For instance, although green tea extract led to statistically significant improvements in lesion counts, it did not result in statistically significant improvements in quality of life, suggesting the observed lesion count differences may not be clinically meaningful to patients.”
And while probiotics had the most studies supporting their efficacy, they were generally of very small sample size.
Asked to comment on the study, Jonette Keri, MD, PhD, a dermatologist who directs the Acne and Rosacea Treatment Center at the University of Miami, who was not involved with the study, said that while the review was exhaustive, more research is needed to better determine the efficacy and side effects of the products studied. “The real strength of this wonderful review is now we have all of this information in one place, and this will serve as a great patient care resource,” she told this news organization.
Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Keri disclosed that she is a consultant for L’Oréal.
.
“While many topical and systemic prescription options are available for the treatment of acne, some patients may be interested in natural and complementary therapies as either an adjunctive or an alternative to prescription medications,” researchers led by John S. Barbieri, MD, MBA, of the department of dermatology at Brigham and Women’s Hospital, Boston, wrote in their study, which was published online in JAMA Dermatology. The researchers defined nutraceuticals as products derived from food sources that provide both nutritional and medicinal benefits, such as vitamins, dietary supplements, and herbal products. “Although patients may be interested in nutraceuticals as a potential treatment option for acne, there is uncertainty regarding the efficacy and safety of these products,” they wrote.
For the systematic review, they searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception through January 30, 2023, to identify randomized clinical trials that evaluated oral nutraceutical interventions such as vitamins and minerals, botanical extracts, prebiotics, and probiotics in individuals with acne. They extracted clinician-reported outcomes, patient-reported outcomes, and adverse events from the included studies, and used the Cochrane Risk of Bias checklist tool to assess the quality of evidence in randomized clinical trials. Based on this tool, they used Agency for Healthcare Research and Quality standards to categorize the articles as good, fair, or poor quality.
The search yielded 42 unique studies with 3,346 participants. Of these 42 studies, 27 were considered poor quality, 11 were considered fair quality, and 4 were considered good quality. The good-quality studies separately evaluated four interventions: vitamin D, green tea extract, probiotics, and cheongsangbangpoong-tang, an herbal formula approved for use in acne by the Korea Food and Drug Administration.
The 11 fair-quality studies suggested potential effectiveness for pantothenic acid (vitamin B5), the fatty acids omega-3 (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) and omega-6 (gamma-linoleic acid), and probiotics.
Zinc was the most studied nutraceutical identified in the review, but “there was substantial heterogeneity in the results, with only slightly greater than one-half of studies finding zinc to be efficacious,” the authors noted. “Studies using higher doses more often found zinc to be efficacious,” they said, adding that zinc “had the highest rate of adverse effect reporting of any nutraceuticals assessed in this review.”
Dr. Barbieri and colleagues acknowledged limitations of their analysis, including the fact that few of the nutraceuticals considered to have good or fair evidence for their use were evaluated in more than one study. “In addition, some studies had inconsistent results depending on the outcome measure assessed,” they wrote. “For instance, although green tea extract led to statistically significant improvements in lesion counts, it did not result in statistically significant improvements in quality of life, suggesting the observed lesion count differences may not be clinically meaningful to patients.”
And while probiotics had the most studies supporting their efficacy, they were generally of very small sample size.
Asked to comment on the study, Jonette Keri, MD, PhD, a dermatologist who directs the Acne and Rosacea Treatment Center at the University of Miami, who was not involved with the study, said that while the review was exhaustive, more research is needed to better determine the efficacy and side effects of the products studied. “The real strength of this wonderful review is now we have all of this information in one place, and this will serve as a great patient care resource,” she told this news organization.
Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Keri disclosed that she is a consultant for L’Oréal.
.
“While many topical and systemic prescription options are available for the treatment of acne, some patients may be interested in natural and complementary therapies as either an adjunctive or an alternative to prescription medications,” researchers led by John S. Barbieri, MD, MBA, of the department of dermatology at Brigham and Women’s Hospital, Boston, wrote in their study, which was published online in JAMA Dermatology. The researchers defined nutraceuticals as products derived from food sources that provide both nutritional and medicinal benefits, such as vitamins, dietary supplements, and herbal products. “Although patients may be interested in nutraceuticals as a potential treatment option for acne, there is uncertainty regarding the efficacy and safety of these products,” they wrote.
For the systematic review, they searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception through January 30, 2023, to identify randomized clinical trials that evaluated oral nutraceutical interventions such as vitamins and minerals, botanical extracts, prebiotics, and probiotics in individuals with acne. They extracted clinician-reported outcomes, patient-reported outcomes, and adverse events from the included studies, and used the Cochrane Risk of Bias checklist tool to assess the quality of evidence in randomized clinical trials. Based on this tool, they used Agency for Healthcare Research and Quality standards to categorize the articles as good, fair, or poor quality.
The search yielded 42 unique studies with 3,346 participants. Of these 42 studies, 27 were considered poor quality, 11 were considered fair quality, and 4 were considered good quality. The good-quality studies separately evaluated four interventions: vitamin D, green tea extract, probiotics, and cheongsangbangpoong-tang, an herbal formula approved for use in acne by the Korea Food and Drug Administration.
The 11 fair-quality studies suggested potential effectiveness for pantothenic acid (vitamin B5), the fatty acids omega-3 (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) and omega-6 (gamma-linoleic acid), and probiotics.
Zinc was the most studied nutraceutical identified in the review, but “there was substantial heterogeneity in the results, with only slightly greater than one-half of studies finding zinc to be efficacious,” the authors noted. “Studies using higher doses more often found zinc to be efficacious,” they said, adding that zinc “had the highest rate of adverse effect reporting of any nutraceuticals assessed in this review.”
Dr. Barbieri and colleagues acknowledged limitations of their analysis, including the fact that few of the nutraceuticals considered to have good or fair evidence for their use were evaluated in more than one study. “In addition, some studies had inconsistent results depending on the outcome measure assessed,” they wrote. “For instance, although green tea extract led to statistically significant improvements in lesion counts, it did not result in statistically significant improvements in quality of life, suggesting the observed lesion count differences may not be clinically meaningful to patients.”
And while probiotics had the most studies supporting their efficacy, they were generally of very small sample size.
Asked to comment on the study, Jonette Keri, MD, PhD, a dermatologist who directs the Acne and Rosacea Treatment Center at the University of Miami, who was not involved with the study, said that while the review was exhaustive, more research is needed to better determine the efficacy and side effects of the products studied. “The real strength of this wonderful review is now we have all of this information in one place, and this will serve as a great patient care resource,” she told this news organization.
Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Keri disclosed that she is a consultant for L’Oréal.
FROM JAMA DERMATOLOGY
Adolescents with atopic dermatitis more likely to have experienced bullying, study finds
TOPLINE:
METHODOLOGY:
- Adolescents with AD have reported appearance-based bullying.
- To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
- Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.
TAKEAWAY:
- A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
- Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
- Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
- Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).
IN PRACTICE:
“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”
SOURCE:
Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online in JAMA Dermatology.
LIMITATIONS:
Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.
DISCLOSURES:
The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Adolescents with AD have reported appearance-based bullying.
- To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
- Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.
TAKEAWAY:
- A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
- Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
- Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
- Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).
IN PRACTICE:
“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”
SOURCE:
Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online in JAMA Dermatology.
LIMITATIONS:
Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.
DISCLOSURES:
The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Adolescents with AD have reported appearance-based bullying.
- To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
- Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.
TAKEAWAY:
- A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
- Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
- Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
- Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).
IN PRACTICE:
“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”
SOURCE:
Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online in JAMA Dermatology.
LIMITATIONS:
Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.
DISCLOSURES:
The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.
A version of this article first appeared on Medscape.com.
FDA approves fixed dose combination topical treatment for acne
vulgaris in patients aged 12 years and older, according to a press release from the manufacturer.
The combination of an antibiotic, a retinoid, and an antibacterial in a gel formulation will be marketed as Cabtreo, and is expected to be available in the first quarter of 2024, according to Ortho Dermatologics.
The treatment was evaluated in a pair of phase 3 multicenter, randomized, controlled trials of 363 patients with moderate to severe acne, according to the company. Approximately 50% of patients across both studies met the primary endpoint of treatment success after 12 weeks of daily use, compared with 24.9% and 20.4% of placebo patients on vehicle in studies 1 and 2, respectively. Treatment success in both studies was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) with scores of clear (0) or almost clear (1), and absolute change from baseline in both inflammatory and noninflammatory lesions. Patients were evaluated at 2, 4, 8, and 12 weeks.
Patients in the treatment groups for both studies had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12, compared with those in the vehicle group. The mean reductions with the treatment vs. vehicle were 75.7% vs. 59.6% and 72.7% vs. 47.6% for inflammatory and noninflammatory lesions, respectively, in study 1, and 80.1% vs. 56.2% and 73.3% vs. 49.0% for inflammatory and noninflammatory lesions, respectively, in study 2.
The most common adverse events were erythema, application-site reactions, pain, irritation, exfoliation, and dermatitis, all of which were more common in the treatment groups vs. the placebo groups.
vulgaris in patients aged 12 years and older, according to a press release from the manufacturer.
The combination of an antibiotic, a retinoid, and an antibacterial in a gel formulation will be marketed as Cabtreo, and is expected to be available in the first quarter of 2024, according to Ortho Dermatologics.
The treatment was evaluated in a pair of phase 3 multicenter, randomized, controlled trials of 363 patients with moderate to severe acne, according to the company. Approximately 50% of patients across both studies met the primary endpoint of treatment success after 12 weeks of daily use, compared with 24.9% and 20.4% of placebo patients on vehicle in studies 1 and 2, respectively. Treatment success in both studies was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) with scores of clear (0) or almost clear (1), and absolute change from baseline in both inflammatory and noninflammatory lesions. Patients were evaluated at 2, 4, 8, and 12 weeks.
Patients in the treatment groups for both studies had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12, compared with those in the vehicle group. The mean reductions with the treatment vs. vehicle were 75.7% vs. 59.6% and 72.7% vs. 47.6% for inflammatory and noninflammatory lesions, respectively, in study 1, and 80.1% vs. 56.2% and 73.3% vs. 49.0% for inflammatory and noninflammatory lesions, respectively, in study 2.
The most common adverse events were erythema, application-site reactions, pain, irritation, exfoliation, and dermatitis, all of which were more common in the treatment groups vs. the placebo groups.
vulgaris in patients aged 12 years and older, according to a press release from the manufacturer.
The combination of an antibiotic, a retinoid, and an antibacterial in a gel formulation will be marketed as Cabtreo, and is expected to be available in the first quarter of 2024, according to Ortho Dermatologics.
The treatment was evaluated in a pair of phase 3 multicenter, randomized, controlled trials of 363 patients with moderate to severe acne, according to the company. Approximately 50% of patients across both studies met the primary endpoint of treatment success after 12 weeks of daily use, compared with 24.9% and 20.4% of placebo patients on vehicle in studies 1 and 2, respectively. Treatment success in both studies was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) with scores of clear (0) or almost clear (1), and absolute change from baseline in both inflammatory and noninflammatory lesions. Patients were evaluated at 2, 4, 8, and 12 weeks.
Patients in the treatment groups for both studies had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12, compared with those in the vehicle group. The mean reductions with the treatment vs. vehicle were 75.7% vs. 59.6% and 72.7% vs. 47.6% for inflammatory and noninflammatory lesions, respectively, in study 1, and 80.1% vs. 56.2% and 73.3% vs. 49.0% for inflammatory and noninflammatory lesions, respectively, in study 2.
The most common adverse events were erythema, application-site reactions, pain, irritation, exfoliation, and dermatitis, all of which were more common in the treatment groups vs. the placebo groups.
Recombinant IL-2 shows potential in atopic dermatitis
BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.
The research was presented at the annual congress of the European Academy of Dermatology and Venereology.
, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.
“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.
“For me, this is proof of concept for so many things, and it gets me very excited.”
Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”
He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”
Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.
Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”
Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”
He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”
At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.
Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.
Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”
To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.
Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.
The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.
Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.
Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.
The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.
By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).
Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.
There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.
The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).
Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.
A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.
Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.
Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.
The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.
The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.
Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.
A version of this article appeared on Medscape.com.
BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.
The research was presented at the annual congress of the European Academy of Dermatology and Venereology.
, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.
“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.
“For me, this is proof of concept for so many things, and it gets me very excited.”
Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”
He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”
Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.
Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”
Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”
He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”
At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.
Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.
Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”
To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.
Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.
The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.
Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.
Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.
The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.
By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).
Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.
There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.
The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).
Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.
A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.
Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.
Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.
The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.
The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.
Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.
A version of this article appeared on Medscape.com.
BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.
The research was presented at the annual congress of the European Academy of Dermatology and Venereology.
, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.
“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.
“For me, this is proof of concept for so many things, and it gets me very excited.”
Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”
He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”
Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.
Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”
Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”
He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”
At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.
Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.
Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”
To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.
Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.
The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.
Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.
Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.
The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.
By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).
Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.
There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.
The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).
Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.
A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.
Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.
Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.
The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.
The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.
Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.
A version of this article appeared on Medscape.com.
AT THE EADV CONGRESS
Treatment options for vitiligo reviewed
CARLSBAD, CALIF. – According to Delphine J. Lee, MD, PhD, some patients report that their dermatologists tell them there are no effective treatments for vitiligo.
However, this is not supported by the ongoing level of research on vitiligo, with more than 100 randomized controlled trials published over the last 5 years, Dr. Lee, chief of dermatology at Harbor-UCLA Medical Center, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. And, in 2022, ruxolitinib cream became the first FDA-approved treatment for vitiligo. “There’s a lot of research happening now, and I’m pleased to say that despite the fact that some of these medications are not all brand new and exciting, they’re still new in that we have new evidence for them,” she said. “Of the 100 randomized, controlled trials, UV therapy remains a strong part of our armamentarium.”
Stabilizing disease
Dr. Lee underscored the importance of stabilizing existing vitiligo and arresting progressive disease, which may be indicated by four key signs: koebnerization; trichrome lesions; inflammation, which can appear as erythema, scaling, and pruritus; and confetti-like macules that are typically 1 mm to 5 mm in size. Key principles of vitiligo treatment are to stop immune destruction and to stimulate melanocyte differentiation, migration, and melanin production, which is “probably why phototherapy is so important and helpful,” she said.
Managing patients’ expectations is also important, added Dr. Lee, who shows patients photos from published clinical trials “so they can see what excellent repigmentation really means.”
Dexamethasone vs. mycophenolate
In a randomized, controlled trial published in 2021, researchers compared dexamethasone oral mini-pulse (OMP), 2.5 mg, on two successive days a week, with oral mycophenolate mofetil, 500 mg b.i.d., up to 2 g every day, for 180 days as a stabilizing treatment for patients with progressive, nonsegmental vitiligo, with 90 days of treatment-free follow-up. Assessments included the vitiligo disease activity (VIDA) score, the number of new lesions in the past 30 days, and the Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in the previous 30 days.
Over the treatment and follow-up period, both groups showed a significant trend for reduction in VIDA and in the number of new lesions in the previous 30 days, compared with baseline (P < .001). The difference between VASI at baseline and VASI at 180 and at 270 days was not significant in both groups.
Adverse side effects reported with dexamethasone included acne, weight gain, headache, insomnia, and menstrual irregularity. “The misconception is that because we only give patients a tiny dose of steroids – 2.5 mg two days per week – that they aren’t going to have any side effects,” Dr. Lee commented. “But in fact, they do.” The most common side effects with mycophenolate were nausea and diarrhea. Two patients on mycophenolate discontinued treatment: one for leukopenia and one for transaminitis, but both conditions resolved after treatment was stopped.
The researchers concluded that both dexamethasone OMP and mycophenolate mofetil halt actively spreading vitiligo. “Relapse occurred earlier with mycophenolate, and the relapse rate was higher than with dexamethasone OMP, but this was not statistically significant,” said Dr. Lee, who also leads an immunology research team at The Lundquist Institute at Harbor-UCLA Medical Center.
Other vitiligo treatment options she discussed included the following:
Betamethasone OMP and oral azathioprine. In a comparative study, researchers compared betamethasone OMP with oral azathioprine in arresting disease progression and inducing repigmentation in adults with vitiligo. Significantly more patients in the betamethasone OMP group achieved arrest of progression at 2 months than those in the azathioprine group, but at 6 months the difference was not significant. At 6 months, of the 19 patients who completed 6 months of betamethasone OMP, 2, 2, and 9 patients had more than 20%, 10%-20%, and 5%-10% repigmentation, respectively; and of the 18 patients who completed 6 months of azathioprine, 2 patients had 10%-20% repigmentation, with the remaining patients having no repigmentation or less than 5% repigmentation.
One patient in the azathioprine group developed acute pancreatitis but none developed transaminitis or leukopenia. “Azathioprine is another agent to add to our toolbox,” Dr. Lee said of the study findings. “Both betamethasone OMP and daily azathioprine are effective” in halting disease progression.
Low-dose cyclosporine. In a comparative study, 50 patients with active vitiligo were randomized into two groups: 25 to dexamethasone OMP 2.5 mg on two consecutive days/week for 4 months, and 25 to cyclosporine 3 mg/kg per day for 4 months, stopped treatment, and were then followed up for another 2 months. After 6 months, 84% of patients in the dexamethasone OMP group and 88% of patients in the cyclosporine group achieved arrest of disease progression (P = 1.00), but the mean time to achieve that endpoint was shorter for those in the cyclosporine group, compared with those in the dexamethasone OMP group (a mean of 3.92 weeks vs. 4.12 weeks, respectively; P = .01).
The list of adverse side effects for cyclosporine was “quite lengthy compared to the usual you would expect for dexamethasone,” said Dr. Lee, who was not involved with the study. “This is something we want to take seriously and discuss with our patients. Still, I would say that low-dose cyclosporine is another possibility to add to our toolbox.”
Phototherapy combined with polypodium leucotomos. Dr. Lee highlighted a randomized, controlled trial in which 21 patients with generalized vitiligo received narrow band (NB)-UVB phototherapy plus polypodium leucotomos extract (480 mg b.i.d.) and 21 patients received NB-UVB phototherapy plus placebo. After 6 months of treatment, patients in the NB-UVB plus oral polypodium leucotomos extract group had a better response rate, compared with those in the NB-UVB plus placebo group (47.8% vs. 22%). “We know from studies of polypodium leucotomos that it seems to have an impact on adaptive immunity as well as helps to decrease oxidative stress, so that may help with melanocyte stability in vitiligo,” said Dr. Lee, who was not affiliated with the study. “As with all treatments, the head and neck is very responsive to this combination treatment. The next most responsive area would be the trunk, followed by the extremities, and hands, and feet.”
Topical treatments
What about topical options for vitiligo? In a randomized, double-blind, comparative study, researchers evaluated the efficacy and safety of combination treatment with 308-nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, followed by topical medication alone for 12 weeks. Calcipotriol 0.005% ointment was applied on one hand vs. clobetasol propionate 0.05% ointment on the other for 24 weeks.
Of the hands treated with excimer light and calcipotriol, 7.7% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol-based and clobetasol-based regimens showed some repigmentation at the end of the study, respectively (P < .05). However, no significant difference was found between the two treatments. “The evaluation from study participants was similar in that they felt that there was clearly a difference from baseline, but there was no difference across the two-hand therapy,” Dr. Lee said.
Adverse side effects included the development of blisters in some of patients who received clobetasol. “The take-home here is that you get excellent repigmentation with calcipotriol, though it’s a small percentage, 7.7%,” Dr. Lee said. “No excellent repigmentation was observed with excimer light and topical clobetasol. These data support two possible topical regimens that could be added to phototherapy or excimer light therapy to improve results.”
In another study of 42 patients, researchers compared twice-daily tacrolimus 0.1% ointment with vehicle for facial vitiligo through 24 weeks of intervention and 24 weeks of follow-up. The researchers defined treatment success as a change of 75% or greater in repigmentation of the target lesion between baseline and week 24, as measured by computer imaging software.
They found that 65% of tacrolimus-treated patients achieved therapeutic success, compared with none of the vehicle-treated patients at week 24 (P < .0001). “Tacrolimus is thought to be an old drug, but it does deserve to have continued proper study based on much anecdotal evidence I hear,” Dr. Lee said. “There was also efficacy over vehicle during the 24 weeks of follow-up. I find that tacrolimus works very well on the face. I’ve had very good results in children.”
Another topical option is the cream formulation of the JAK inhibitor ruxolitinib (Opzelura), approved in 2022 for the treatment of nonsegmental vitiligo in patients ages 12 and older, the first FDA-approved treatment for vitiligo. “As with the tacrolimus study, there are patients who achieve 100% repigmentation [with ruxolitinib], but others who may not,” Dr. Lee said. In addition, she noted that the combination of JAK inhibitors with phototherapy is emerging as another possible treatment choice, referring to a recently published systematic review suggesting that concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.
Dr. Lee reported having no relevant financial disclosures.
CARLSBAD, CALIF. – According to Delphine J. Lee, MD, PhD, some patients report that their dermatologists tell them there are no effective treatments for vitiligo.
However, this is not supported by the ongoing level of research on vitiligo, with more than 100 randomized controlled trials published over the last 5 years, Dr. Lee, chief of dermatology at Harbor-UCLA Medical Center, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. And, in 2022, ruxolitinib cream became the first FDA-approved treatment for vitiligo. “There’s a lot of research happening now, and I’m pleased to say that despite the fact that some of these medications are not all brand new and exciting, they’re still new in that we have new evidence for them,” she said. “Of the 100 randomized, controlled trials, UV therapy remains a strong part of our armamentarium.”
Stabilizing disease
Dr. Lee underscored the importance of stabilizing existing vitiligo and arresting progressive disease, which may be indicated by four key signs: koebnerization; trichrome lesions; inflammation, which can appear as erythema, scaling, and pruritus; and confetti-like macules that are typically 1 mm to 5 mm in size. Key principles of vitiligo treatment are to stop immune destruction and to stimulate melanocyte differentiation, migration, and melanin production, which is “probably why phototherapy is so important and helpful,” she said.
Managing patients’ expectations is also important, added Dr. Lee, who shows patients photos from published clinical trials “so they can see what excellent repigmentation really means.”
Dexamethasone vs. mycophenolate
In a randomized, controlled trial published in 2021, researchers compared dexamethasone oral mini-pulse (OMP), 2.5 mg, on two successive days a week, with oral mycophenolate mofetil, 500 mg b.i.d., up to 2 g every day, for 180 days as a stabilizing treatment for patients with progressive, nonsegmental vitiligo, with 90 days of treatment-free follow-up. Assessments included the vitiligo disease activity (VIDA) score, the number of new lesions in the past 30 days, and the Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in the previous 30 days.
Over the treatment and follow-up period, both groups showed a significant trend for reduction in VIDA and in the number of new lesions in the previous 30 days, compared with baseline (P < .001). The difference between VASI at baseline and VASI at 180 and at 270 days was not significant in both groups.
Adverse side effects reported with dexamethasone included acne, weight gain, headache, insomnia, and menstrual irregularity. “The misconception is that because we only give patients a tiny dose of steroids – 2.5 mg two days per week – that they aren’t going to have any side effects,” Dr. Lee commented. “But in fact, they do.” The most common side effects with mycophenolate were nausea and diarrhea. Two patients on mycophenolate discontinued treatment: one for leukopenia and one for transaminitis, but both conditions resolved after treatment was stopped.
The researchers concluded that both dexamethasone OMP and mycophenolate mofetil halt actively spreading vitiligo. “Relapse occurred earlier with mycophenolate, and the relapse rate was higher than with dexamethasone OMP, but this was not statistically significant,” said Dr. Lee, who also leads an immunology research team at The Lundquist Institute at Harbor-UCLA Medical Center.
Other vitiligo treatment options she discussed included the following:
Betamethasone OMP and oral azathioprine. In a comparative study, researchers compared betamethasone OMP with oral azathioprine in arresting disease progression and inducing repigmentation in adults with vitiligo. Significantly more patients in the betamethasone OMP group achieved arrest of progression at 2 months than those in the azathioprine group, but at 6 months the difference was not significant. At 6 months, of the 19 patients who completed 6 months of betamethasone OMP, 2, 2, and 9 patients had more than 20%, 10%-20%, and 5%-10% repigmentation, respectively; and of the 18 patients who completed 6 months of azathioprine, 2 patients had 10%-20% repigmentation, with the remaining patients having no repigmentation or less than 5% repigmentation.
One patient in the azathioprine group developed acute pancreatitis but none developed transaminitis or leukopenia. “Azathioprine is another agent to add to our toolbox,” Dr. Lee said of the study findings. “Both betamethasone OMP and daily azathioprine are effective” in halting disease progression.
Low-dose cyclosporine. In a comparative study, 50 patients with active vitiligo were randomized into two groups: 25 to dexamethasone OMP 2.5 mg on two consecutive days/week for 4 months, and 25 to cyclosporine 3 mg/kg per day for 4 months, stopped treatment, and were then followed up for another 2 months. After 6 months, 84% of patients in the dexamethasone OMP group and 88% of patients in the cyclosporine group achieved arrest of disease progression (P = 1.00), but the mean time to achieve that endpoint was shorter for those in the cyclosporine group, compared with those in the dexamethasone OMP group (a mean of 3.92 weeks vs. 4.12 weeks, respectively; P = .01).
The list of adverse side effects for cyclosporine was “quite lengthy compared to the usual you would expect for dexamethasone,” said Dr. Lee, who was not involved with the study. “This is something we want to take seriously and discuss with our patients. Still, I would say that low-dose cyclosporine is another possibility to add to our toolbox.”
Phototherapy combined with polypodium leucotomos. Dr. Lee highlighted a randomized, controlled trial in which 21 patients with generalized vitiligo received narrow band (NB)-UVB phototherapy plus polypodium leucotomos extract (480 mg b.i.d.) and 21 patients received NB-UVB phototherapy plus placebo. After 6 months of treatment, patients in the NB-UVB plus oral polypodium leucotomos extract group had a better response rate, compared with those in the NB-UVB plus placebo group (47.8% vs. 22%). “We know from studies of polypodium leucotomos that it seems to have an impact on adaptive immunity as well as helps to decrease oxidative stress, so that may help with melanocyte stability in vitiligo,” said Dr. Lee, who was not affiliated with the study. “As with all treatments, the head and neck is very responsive to this combination treatment. The next most responsive area would be the trunk, followed by the extremities, and hands, and feet.”
Topical treatments
What about topical options for vitiligo? In a randomized, double-blind, comparative study, researchers evaluated the efficacy and safety of combination treatment with 308-nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, followed by topical medication alone for 12 weeks. Calcipotriol 0.005% ointment was applied on one hand vs. clobetasol propionate 0.05% ointment on the other for 24 weeks.
Of the hands treated with excimer light and calcipotriol, 7.7% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol-based and clobetasol-based regimens showed some repigmentation at the end of the study, respectively (P < .05). However, no significant difference was found between the two treatments. “The evaluation from study participants was similar in that they felt that there was clearly a difference from baseline, but there was no difference across the two-hand therapy,” Dr. Lee said.
Adverse side effects included the development of blisters in some of patients who received clobetasol. “The take-home here is that you get excellent repigmentation with calcipotriol, though it’s a small percentage, 7.7%,” Dr. Lee said. “No excellent repigmentation was observed with excimer light and topical clobetasol. These data support two possible topical regimens that could be added to phototherapy or excimer light therapy to improve results.”
In another study of 42 patients, researchers compared twice-daily tacrolimus 0.1% ointment with vehicle for facial vitiligo through 24 weeks of intervention and 24 weeks of follow-up. The researchers defined treatment success as a change of 75% or greater in repigmentation of the target lesion between baseline and week 24, as measured by computer imaging software.
They found that 65% of tacrolimus-treated patients achieved therapeutic success, compared with none of the vehicle-treated patients at week 24 (P < .0001). “Tacrolimus is thought to be an old drug, but it does deserve to have continued proper study based on much anecdotal evidence I hear,” Dr. Lee said. “There was also efficacy over vehicle during the 24 weeks of follow-up. I find that tacrolimus works very well on the face. I’ve had very good results in children.”
Another topical option is the cream formulation of the JAK inhibitor ruxolitinib (Opzelura), approved in 2022 for the treatment of nonsegmental vitiligo in patients ages 12 and older, the first FDA-approved treatment for vitiligo. “As with the tacrolimus study, there are patients who achieve 100% repigmentation [with ruxolitinib], but others who may not,” Dr. Lee said. In addition, she noted that the combination of JAK inhibitors with phototherapy is emerging as another possible treatment choice, referring to a recently published systematic review suggesting that concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.
Dr. Lee reported having no relevant financial disclosures.
CARLSBAD, CALIF. – According to Delphine J. Lee, MD, PhD, some patients report that their dermatologists tell them there are no effective treatments for vitiligo.
However, this is not supported by the ongoing level of research on vitiligo, with more than 100 randomized controlled trials published over the last 5 years, Dr. Lee, chief of dermatology at Harbor-UCLA Medical Center, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. And, in 2022, ruxolitinib cream became the first FDA-approved treatment for vitiligo. “There’s a lot of research happening now, and I’m pleased to say that despite the fact that some of these medications are not all brand new and exciting, they’re still new in that we have new evidence for them,” she said. “Of the 100 randomized, controlled trials, UV therapy remains a strong part of our armamentarium.”
Stabilizing disease
Dr. Lee underscored the importance of stabilizing existing vitiligo and arresting progressive disease, which may be indicated by four key signs: koebnerization; trichrome lesions; inflammation, which can appear as erythema, scaling, and pruritus; and confetti-like macules that are typically 1 mm to 5 mm in size. Key principles of vitiligo treatment are to stop immune destruction and to stimulate melanocyte differentiation, migration, and melanin production, which is “probably why phototherapy is so important and helpful,” she said.
Managing patients’ expectations is also important, added Dr. Lee, who shows patients photos from published clinical trials “so they can see what excellent repigmentation really means.”
Dexamethasone vs. mycophenolate
In a randomized, controlled trial published in 2021, researchers compared dexamethasone oral mini-pulse (OMP), 2.5 mg, on two successive days a week, with oral mycophenolate mofetil, 500 mg b.i.d., up to 2 g every day, for 180 days as a stabilizing treatment for patients with progressive, nonsegmental vitiligo, with 90 days of treatment-free follow-up. Assessments included the vitiligo disease activity (VIDA) score, the number of new lesions in the past 30 days, and the Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in the previous 30 days.
Over the treatment and follow-up period, both groups showed a significant trend for reduction in VIDA and in the number of new lesions in the previous 30 days, compared with baseline (P < .001). The difference between VASI at baseline and VASI at 180 and at 270 days was not significant in both groups.
Adverse side effects reported with dexamethasone included acne, weight gain, headache, insomnia, and menstrual irregularity. “The misconception is that because we only give patients a tiny dose of steroids – 2.5 mg two days per week – that they aren’t going to have any side effects,” Dr. Lee commented. “But in fact, they do.” The most common side effects with mycophenolate were nausea and diarrhea. Two patients on mycophenolate discontinued treatment: one for leukopenia and one for transaminitis, but both conditions resolved after treatment was stopped.
The researchers concluded that both dexamethasone OMP and mycophenolate mofetil halt actively spreading vitiligo. “Relapse occurred earlier with mycophenolate, and the relapse rate was higher than with dexamethasone OMP, but this was not statistically significant,” said Dr. Lee, who also leads an immunology research team at The Lundquist Institute at Harbor-UCLA Medical Center.
Other vitiligo treatment options she discussed included the following:
Betamethasone OMP and oral azathioprine. In a comparative study, researchers compared betamethasone OMP with oral azathioprine in arresting disease progression and inducing repigmentation in adults with vitiligo. Significantly more patients in the betamethasone OMP group achieved arrest of progression at 2 months than those in the azathioprine group, but at 6 months the difference was not significant. At 6 months, of the 19 patients who completed 6 months of betamethasone OMP, 2, 2, and 9 patients had more than 20%, 10%-20%, and 5%-10% repigmentation, respectively; and of the 18 patients who completed 6 months of azathioprine, 2 patients had 10%-20% repigmentation, with the remaining patients having no repigmentation or less than 5% repigmentation.
One patient in the azathioprine group developed acute pancreatitis but none developed transaminitis or leukopenia. “Azathioprine is another agent to add to our toolbox,” Dr. Lee said of the study findings. “Both betamethasone OMP and daily azathioprine are effective” in halting disease progression.
Low-dose cyclosporine. In a comparative study, 50 patients with active vitiligo were randomized into two groups: 25 to dexamethasone OMP 2.5 mg on two consecutive days/week for 4 months, and 25 to cyclosporine 3 mg/kg per day for 4 months, stopped treatment, and were then followed up for another 2 months. After 6 months, 84% of patients in the dexamethasone OMP group and 88% of patients in the cyclosporine group achieved arrest of disease progression (P = 1.00), but the mean time to achieve that endpoint was shorter for those in the cyclosporine group, compared with those in the dexamethasone OMP group (a mean of 3.92 weeks vs. 4.12 weeks, respectively; P = .01).
The list of adverse side effects for cyclosporine was “quite lengthy compared to the usual you would expect for dexamethasone,” said Dr. Lee, who was not involved with the study. “This is something we want to take seriously and discuss with our patients. Still, I would say that low-dose cyclosporine is another possibility to add to our toolbox.”
Phototherapy combined with polypodium leucotomos. Dr. Lee highlighted a randomized, controlled trial in which 21 patients with generalized vitiligo received narrow band (NB)-UVB phototherapy plus polypodium leucotomos extract (480 mg b.i.d.) and 21 patients received NB-UVB phototherapy plus placebo. After 6 months of treatment, patients in the NB-UVB plus oral polypodium leucotomos extract group had a better response rate, compared with those in the NB-UVB plus placebo group (47.8% vs. 22%). “We know from studies of polypodium leucotomos that it seems to have an impact on adaptive immunity as well as helps to decrease oxidative stress, so that may help with melanocyte stability in vitiligo,” said Dr. Lee, who was not affiliated with the study. “As with all treatments, the head and neck is very responsive to this combination treatment. The next most responsive area would be the trunk, followed by the extremities, and hands, and feet.”
Topical treatments
What about topical options for vitiligo? In a randomized, double-blind, comparative study, researchers evaluated the efficacy and safety of combination treatment with 308-nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, followed by topical medication alone for 12 weeks. Calcipotriol 0.005% ointment was applied on one hand vs. clobetasol propionate 0.05% ointment on the other for 24 weeks.
Of the hands treated with excimer light and calcipotriol, 7.7% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol-based and clobetasol-based regimens showed some repigmentation at the end of the study, respectively (P < .05). However, no significant difference was found between the two treatments. “The evaluation from study participants was similar in that they felt that there was clearly a difference from baseline, but there was no difference across the two-hand therapy,” Dr. Lee said.
Adverse side effects included the development of blisters in some of patients who received clobetasol. “The take-home here is that you get excellent repigmentation with calcipotriol, though it’s a small percentage, 7.7%,” Dr. Lee said. “No excellent repigmentation was observed with excimer light and topical clobetasol. These data support two possible topical regimens that could be added to phototherapy or excimer light therapy to improve results.”
In another study of 42 patients, researchers compared twice-daily tacrolimus 0.1% ointment with vehicle for facial vitiligo through 24 weeks of intervention and 24 weeks of follow-up. The researchers defined treatment success as a change of 75% or greater in repigmentation of the target lesion between baseline and week 24, as measured by computer imaging software.
They found that 65% of tacrolimus-treated patients achieved therapeutic success, compared with none of the vehicle-treated patients at week 24 (P < .0001). “Tacrolimus is thought to be an old drug, but it does deserve to have continued proper study based on much anecdotal evidence I hear,” Dr. Lee said. “There was also efficacy over vehicle during the 24 weeks of follow-up. I find that tacrolimus works very well on the face. I’ve had very good results in children.”
Another topical option is the cream formulation of the JAK inhibitor ruxolitinib (Opzelura), approved in 2022 for the treatment of nonsegmental vitiligo in patients ages 12 and older, the first FDA-approved treatment for vitiligo. “As with the tacrolimus study, there are patients who achieve 100% repigmentation [with ruxolitinib], but others who may not,” Dr. Lee said. In addition, she noted that the combination of JAK inhibitors with phototherapy is emerging as another possible treatment choice, referring to a recently published systematic review suggesting that concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.
Dr. Lee reported having no relevant financial disclosures.
AT CALDERM 2023
Psoriatic disease: Researchers seek a PsA diagnostic test, phenotype-targeted treatment
WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.
“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.
“We know that mechanistically, there is dominance of the IL [interleukin]-23 and IL-17 pathways, as well as TNF [tumor necrosis factor], but we think there are tissue-specific cellular interactions [and] other pathways and mechanisms to be defined, and the goal now is to go into the tissues to find out,” he said at the meeting.
Dr. Ritchlin is co-leading a new research team dedicated to psoriatic spectrum diseases as part of the $64.5 million Autoimmune and Immune-Mediated Diseases Program (AIM) of the Accelerating Medicine Partnership (AMP), a huge public-private partnership involving the National Institutes of Health that is collecting and analyzing troves of biological data in order to better understand the cellular and molecular compositions and interactions that lead to disease.
As part of its work, this eight-center project – coined ELLIPSS, for Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium – hopes to define at a molecular and single-cell level how the transition to PsA unfolds in the setting of psoriasis. Up to 30% of patients with cutaneous psoriasis also develop PsA.
The NPF, meanwhile, has invested over $3 million for research and development and validation of a diagnostic test for PsA – one that could potentially be used by dermatologists and primary care physicians to decrease the time to diagnosis. Researchers like Jose U. Scher, MD, director of the Psoriatic Arthritis Center at New York University and the NYU Colton Center for Autoimmunity, are in the thick of using multiple “-omics” tools and other sophisticated technologies to identify new targets and biomarkers.
As this work unfolds over the next several years, there is growing interest in combination therapy for PsA, Dr. Scher and Dr. Ritchlin said, and in addressing extra-articular traits, such as obesity and centralized pain, that are believed to have an impact on disease and on response to treatment.
A deep dive into the tissue
Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.
The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.
Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.
“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”
The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.
Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.
Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.
With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”
The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
Finding biomarkers, diagnostic signatures
The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”
A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.
Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.
Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.
At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)
Dr. Scher has also focused on skin microbiomics in looking for biomarkers for the transition to PsA. “There are potential biomarkers ... that need to be validated and expanded. We have clues,” he said at the meeting, noting that microbial signatures from nonlesional skin appear to differentiate psoriasis from PsA.
The microbiome of the skin and of the gut will also be investigated by the ELLIPPS team as they analyze biosamples and try to define psoriasis and PsA endotypes. The microbiome “is critical to psoriasis and PsA,” Dr. Ritchlin said at the meeting. “I think [our knowledge] will really expand dramatically in the next 5 years.”
Wilson Liao, MD, professor and associate vice-chair of research in the department of dermatology at the University of California, San Francisco, whose work has contributed to development of a diagnostic test, was among several experts who emphasized the importance of early diagnosis in the prevention of joint damage. Identifying the disease, he said, is “one of our true unmet needs” in psoriasis.
Dr. Liao’s research identified genes and proteins differentially expressed in PsA, psoriasis, and healthy subjects across 30 immune cells types and then identified potential biomarkers through machine learning classification of these genes and proteins along with previously published genetic risk factors for PsA.
Eyes on combination therapy
“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”
Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.
A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.
In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”
It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.
In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”
Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.
WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.
“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.
“We know that mechanistically, there is dominance of the IL [interleukin]-23 and IL-17 pathways, as well as TNF [tumor necrosis factor], but we think there are tissue-specific cellular interactions [and] other pathways and mechanisms to be defined, and the goal now is to go into the tissues to find out,” he said at the meeting.
Dr. Ritchlin is co-leading a new research team dedicated to psoriatic spectrum diseases as part of the $64.5 million Autoimmune and Immune-Mediated Diseases Program (AIM) of the Accelerating Medicine Partnership (AMP), a huge public-private partnership involving the National Institutes of Health that is collecting and analyzing troves of biological data in order to better understand the cellular and molecular compositions and interactions that lead to disease.
As part of its work, this eight-center project – coined ELLIPSS, for Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium – hopes to define at a molecular and single-cell level how the transition to PsA unfolds in the setting of psoriasis. Up to 30% of patients with cutaneous psoriasis also develop PsA.
The NPF, meanwhile, has invested over $3 million for research and development and validation of a diagnostic test for PsA – one that could potentially be used by dermatologists and primary care physicians to decrease the time to diagnosis. Researchers like Jose U. Scher, MD, director of the Psoriatic Arthritis Center at New York University and the NYU Colton Center for Autoimmunity, are in the thick of using multiple “-omics” tools and other sophisticated technologies to identify new targets and biomarkers.
As this work unfolds over the next several years, there is growing interest in combination therapy for PsA, Dr. Scher and Dr. Ritchlin said, and in addressing extra-articular traits, such as obesity and centralized pain, that are believed to have an impact on disease and on response to treatment.
A deep dive into the tissue
Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.
The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.
Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.
“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”
The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.
Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.
Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.
With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”
The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
Finding biomarkers, diagnostic signatures
The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”
A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.
Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.
Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.
At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)
Dr. Scher has also focused on skin microbiomics in looking for biomarkers for the transition to PsA. “There are potential biomarkers ... that need to be validated and expanded. We have clues,” he said at the meeting, noting that microbial signatures from nonlesional skin appear to differentiate psoriasis from PsA.
The microbiome of the skin and of the gut will also be investigated by the ELLIPPS team as they analyze biosamples and try to define psoriasis and PsA endotypes. The microbiome “is critical to psoriasis and PsA,” Dr. Ritchlin said at the meeting. “I think [our knowledge] will really expand dramatically in the next 5 years.”
Wilson Liao, MD, professor and associate vice-chair of research in the department of dermatology at the University of California, San Francisco, whose work has contributed to development of a diagnostic test, was among several experts who emphasized the importance of early diagnosis in the prevention of joint damage. Identifying the disease, he said, is “one of our true unmet needs” in psoriasis.
Dr. Liao’s research identified genes and proteins differentially expressed in PsA, psoriasis, and healthy subjects across 30 immune cells types and then identified potential biomarkers through machine learning classification of these genes and proteins along with previously published genetic risk factors for PsA.
Eyes on combination therapy
“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”
Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.
A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.
In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”
It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.
In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”
Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.
WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.
“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.
“We know that mechanistically, there is dominance of the IL [interleukin]-23 and IL-17 pathways, as well as TNF [tumor necrosis factor], but we think there are tissue-specific cellular interactions [and] other pathways and mechanisms to be defined, and the goal now is to go into the tissues to find out,” he said at the meeting.
Dr. Ritchlin is co-leading a new research team dedicated to psoriatic spectrum diseases as part of the $64.5 million Autoimmune and Immune-Mediated Diseases Program (AIM) of the Accelerating Medicine Partnership (AMP), a huge public-private partnership involving the National Institutes of Health that is collecting and analyzing troves of biological data in order to better understand the cellular and molecular compositions and interactions that lead to disease.
As part of its work, this eight-center project – coined ELLIPSS, for Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium – hopes to define at a molecular and single-cell level how the transition to PsA unfolds in the setting of psoriasis. Up to 30% of patients with cutaneous psoriasis also develop PsA.
The NPF, meanwhile, has invested over $3 million for research and development and validation of a diagnostic test for PsA – one that could potentially be used by dermatologists and primary care physicians to decrease the time to diagnosis. Researchers like Jose U. Scher, MD, director of the Psoriatic Arthritis Center at New York University and the NYU Colton Center for Autoimmunity, are in the thick of using multiple “-omics” tools and other sophisticated technologies to identify new targets and biomarkers.
As this work unfolds over the next several years, there is growing interest in combination therapy for PsA, Dr. Scher and Dr. Ritchlin said, and in addressing extra-articular traits, such as obesity and centralized pain, that are believed to have an impact on disease and on response to treatment.
A deep dive into the tissue
Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.
The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.
Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.
“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”
The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.
Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.
Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.
With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”
The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
Finding biomarkers, diagnostic signatures
The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”
A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.
Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.
Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.
At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)
Dr. Scher has also focused on skin microbiomics in looking for biomarkers for the transition to PsA. “There are potential biomarkers ... that need to be validated and expanded. We have clues,” he said at the meeting, noting that microbial signatures from nonlesional skin appear to differentiate psoriasis from PsA.
The microbiome of the skin and of the gut will also be investigated by the ELLIPPS team as they analyze biosamples and try to define psoriasis and PsA endotypes. The microbiome “is critical to psoriasis and PsA,” Dr. Ritchlin said at the meeting. “I think [our knowledge] will really expand dramatically in the next 5 years.”
Wilson Liao, MD, professor and associate vice-chair of research in the department of dermatology at the University of California, San Francisco, whose work has contributed to development of a diagnostic test, was among several experts who emphasized the importance of early diagnosis in the prevention of joint damage. Identifying the disease, he said, is “one of our true unmet needs” in psoriasis.
Dr. Liao’s research identified genes and proteins differentially expressed in PsA, psoriasis, and healthy subjects across 30 immune cells types and then identified potential biomarkers through machine learning classification of these genes and proteins along with previously published genetic risk factors for PsA.
Eyes on combination therapy
“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”
Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.
A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.
In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”
It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.
In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”
Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.
AT THE NPF RESEARCH SYMPOSIUM 2023
Frustrating facial lesions
These tender nodules are classic for cystic acne and are common in women older than 20 years. Instead of outgrowing acne in their teenage years, some people (such as this patient) develop frequent tender cystic acne lesions that often heal with hyperpigmented scars.
Acne is the most prevalent chronic skin condition in the United States, affecting up to 50 million people.1 Approximately 12% of adult women are affected.2 The main contributing factors include increased sebum production, follicular hyperkeratinization, microbial follicular colonization with Propionibacterium acnes, and an inflammatory reaction.3
Treatment is available in both topical and oral forms. Topical antibiotics are used predominantly for treating mild-to-moderate inflammatory acne. They are not recommended as monotherapy due to the risk for bacterial resistance; this can be prevented by adding benzoyl peroxide, which exfoliates and acts as an antibacterial agent. Clindamycin 1% solution or gel is the preferred topical antibiotic for treatment of acne.4
Topical retinoids can be used as monotherapy or in combination with antibiotics. They also can be used for maintenance after treatment goals are reached and systemic antibiotics are discontinued. Retinoids generally are applied in the evening because the sun weakens their effect. Patients on retinoids also are more sensitive to the sun and should be counseled to use sunscreen daily. Counseling on pregnancy risks and appropriate use of contraception also should be offered to patients using retinoids. It is advisable to consider the use of combination oral contraceptives, particularly in women who have adult-onset acne or experience flare-ups around the time of their menstrual cycle.3
Azelaic acid has anticomedonal, antibacterial, and anti-inflammatory properties and may be effective in treating mild-to-moderate inflammatory acne and hyperpigmentation. Salicylic acid also has comedolytic properties, although there have been limited studies examining its effectiveness. Both azelaic and salicylic acid are considered safe for use in pregnancy.
Oral antibiotics are recommended in the treatment of moderate-to-severe acne. Both doxycycline and minocycline are more effective than tetracycline for treating acne, with no clear superiority between the two.4 Macrolides also can be effective in treating acne, although their use should be limited to those who cannot tolerate tetracyclines. Systemic antibiotic use should be limited to 3 to 4 months due to decreasing efficacy over time and to minimize the development of bacterial resistance. If treatment goals are attained, the antibiotics can be replaced with retinoids.
Oral isotretinoin is reserved for treatment of severe nodular acne or moderate acne that is treatment resistant. Patients should be counseled on contraceptive methods, as isotretinoin is highly teratogenic and therefore prescribed through the iPLEDGE program.3,4
Given this patient’s persistent symptoms despite use of topical antibiotics and topical tretinoin, she decided to try oral antibiotics (doxycycline 100 mg twice daily) for 3 months and to start long-term oral contraceptives. If her symptoms continue, she will enroll in the iPLEDGE program and start treatment with oral isotretinoin.
Photo courtesy of Ayo Sorunke, MD. Text courtesy of Ayo Sorunke, MD, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.
1. White GM. Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris. J Am Acad Dermatol. 1998;39:S34-S37. doi: 10.1016/s0190-9622(98)70442-6
2. Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad Dermatol. 1999;41:577-580.
3. Titus S, Hodge J. Diagnosis and treatment of acne. Am Fam Physician. 2012;86:734-740.
4. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-973.e33. doi: 10.1016/j.jaad.2015.12.037
These tender nodules are classic for cystic acne and are common in women older than 20 years. Instead of outgrowing acne in their teenage years, some people (such as this patient) develop frequent tender cystic acne lesions that often heal with hyperpigmented scars.
Acne is the most prevalent chronic skin condition in the United States, affecting up to 50 million people.1 Approximately 12% of adult women are affected.2 The main contributing factors include increased sebum production, follicular hyperkeratinization, microbial follicular colonization with Propionibacterium acnes, and an inflammatory reaction.3
Treatment is available in both topical and oral forms. Topical antibiotics are used predominantly for treating mild-to-moderate inflammatory acne. They are not recommended as monotherapy due to the risk for bacterial resistance; this can be prevented by adding benzoyl peroxide, which exfoliates and acts as an antibacterial agent. Clindamycin 1% solution or gel is the preferred topical antibiotic for treatment of acne.4
Topical retinoids can be used as monotherapy or in combination with antibiotics. They also can be used for maintenance after treatment goals are reached and systemic antibiotics are discontinued. Retinoids generally are applied in the evening because the sun weakens their effect. Patients on retinoids also are more sensitive to the sun and should be counseled to use sunscreen daily. Counseling on pregnancy risks and appropriate use of contraception also should be offered to patients using retinoids. It is advisable to consider the use of combination oral contraceptives, particularly in women who have adult-onset acne or experience flare-ups around the time of their menstrual cycle.3
Azelaic acid has anticomedonal, antibacterial, and anti-inflammatory properties and may be effective in treating mild-to-moderate inflammatory acne and hyperpigmentation. Salicylic acid also has comedolytic properties, although there have been limited studies examining its effectiveness. Both azelaic and salicylic acid are considered safe for use in pregnancy.
Oral antibiotics are recommended in the treatment of moderate-to-severe acne. Both doxycycline and minocycline are more effective than tetracycline for treating acne, with no clear superiority between the two.4 Macrolides also can be effective in treating acne, although their use should be limited to those who cannot tolerate tetracyclines. Systemic antibiotic use should be limited to 3 to 4 months due to decreasing efficacy over time and to minimize the development of bacterial resistance. If treatment goals are attained, the antibiotics can be replaced with retinoids.
Oral isotretinoin is reserved for treatment of severe nodular acne or moderate acne that is treatment resistant. Patients should be counseled on contraceptive methods, as isotretinoin is highly teratogenic and therefore prescribed through the iPLEDGE program.3,4
Given this patient’s persistent symptoms despite use of topical antibiotics and topical tretinoin, she decided to try oral antibiotics (doxycycline 100 mg twice daily) for 3 months and to start long-term oral contraceptives. If her symptoms continue, she will enroll in the iPLEDGE program and start treatment with oral isotretinoin.
Photo courtesy of Ayo Sorunke, MD. Text courtesy of Ayo Sorunke, MD, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.
These tender nodules are classic for cystic acne and are common in women older than 20 years. Instead of outgrowing acne in their teenage years, some people (such as this patient) develop frequent tender cystic acne lesions that often heal with hyperpigmented scars.
Acne is the most prevalent chronic skin condition in the United States, affecting up to 50 million people.1 Approximately 12% of adult women are affected.2 The main contributing factors include increased sebum production, follicular hyperkeratinization, microbial follicular colonization with Propionibacterium acnes, and an inflammatory reaction.3
Treatment is available in both topical and oral forms. Topical antibiotics are used predominantly for treating mild-to-moderate inflammatory acne. They are not recommended as monotherapy due to the risk for bacterial resistance; this can be prevented by adding benzoyl peroxide, which exfoliates and acts as an antibacterial agent. Clindamycin 1% solution or gel is the preferred topical antibiotic for treatment of acne.4
Topical retinoids can be used as monotherapy or in combination with antibiotics. They also can be used for maintenance after treatment goals are reached and systemic antibiotics are discontinued. Retinoids generally are applied in the evening because the sun weakens their effect. Patients on retinoids also are more sensitive to the sun and should be counseled to use sunscreen daily. Counseling on pregnancy risks and appropriate use of contraception also should be offered to patients using retinoids. It is advisable to consider the use of combination oral contraceptives, particularly in women who have adult-onset acne or experience flare-ups around the time of their menstrual cycle.3
Azelaic acid has anticomedonal, antibacterial, and anti-inflammatory properties and may be effective in treating mild-to-moderate inflammatory acne and hyperpigmentation. Salicylic acid also has comedolytic properties, although there have been limited studies examining its effectiveness. Both azelaic and salicylic acid are considered safe for use in pregnancy.
Oral antibiotics are recommended in the treatment of moderate-to-severe acne. Both doxycycline and minocycline are more effective than tetracycline for treating acne, with no clear superiority between the two.4 Macrolides also can be effective in treating acne, although their use should be limited to those who cannot tolerate tetracyclines. Systemic antibiotic use should be limited to 3 to 4 months due to decreasing efficacy over time and to minimize the development of bacterial resistance. If treatment goals are attained, the antibiotics can be replaced with retinoids.
Oral isotretinoin is reserved for treatment of severe nodular acne or moderate acne that is treatment resistant. Patients should be counseled on contraceptive methods, as isotretinoin is highly teratogenic and therefore prescribed through the iPLEDGE program.3,4
Given this patient’s persistent symptoms despite use of topical antibiotics and topical tretinoin, she decided to try oral antibiotics (doxycycline 100 mg twice daily) for 3 months and to start long-term oral contraceptives. If her symptoms continue, she will enroll in the iPLEDGE program and start treatment with oral isotretinoin.
Photo courtesy of Ayo Sorunke, MD. Text courtesy of Ayo Sorunke, MD, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.
1. White GM. Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris. J Am Acad Dermatol. 1998;39:S34-S37. doi: 10.1016/s0190-9622(98)70442-6
2. Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad Dermatol. 1999;41:577-580.
3. Titus S, Hodge J. Diagnosis and treatment of acne. Am Fam Physician. 2012;86:734-740.
4. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-973.e33. doi: 10.1016/j.jaad.2015.12.037
1. White GM. Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris. J Am Acad Dermatol. 1998;39:S34-S37. doi: 10.1016/s0190-9622(98)70442-6
2. Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad Dermatol. 1999;41:577-580.
3. Titus S, Hodge J. Diagnosis and treatment of acne. Am Fam Physician. 2012;86:734-740.
4. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-973.e33. doi: 10.1016/j.jaad.2015.12.037
Teledermatology model takes hold with grants to underserved areas
, according to a press release from the university.
Four institutions will receive grants to implement the George Washington University model, which involved partnering with a local organization to provide an entry point for individuals in areas with limited access to medical care, with support from Pfizer Global Medical Grants.
“Targeting those who lack access to quality-based care for inflammatory dermatologic conditions, including atopic dermatitis (AD) and others, the grants will reach communities in Miami-Dade County, Fla., Los Angeles County, Calif., rural communities in Oregon, and downtown Philadelphia,” according to the announcement. GW’s Teledermatology Free Clinic was conceived in the wake of the COVID-19 pandemic, which further highlighted disparities in access to dermatologic care, Adam Friedman, M.D., professor and chair of dermatology at George Washington University, said in the press release.
GW implemented its clinic for residents in underserved areas of Washington, D.C., in partnership with the Rodham Institute and the Temple of Praise Church. “We set up a free clinic at the church through which patients were integrated into the GW medical records system, provided instruction on telemedicine best practices, exposed to comprehensive education about AD and underwent a free telemedicine visit with a member of the department of dermatology,” Dr. Friedman explained.
Most participants – 70% – did not have a dermatologist, 94% were extremely satisfied with the experience, and 90% reported that the clinic had a significant impact on the management of their AD, according to the results of a recently published postengagement survey.
The following are the recipients of the “Quality Improvement Initiative: Bridging the Inflammatory Dermatosis Care Divide with Teledermatology Grant Program”:
- Scott Elman, MD, assistant professor of clinical dermatology and medical director of outpatient dermatology at the University of Miami and his team will create a clinic in partnership with Lotus House, a resource center and residential facility serving homeless women and infants, with focus on interventions in both English and Spanish.
- Nada Elbuluk, MD, associate professor of clinical dermatology and director of the Skin of Color and Pigmentary Disorders Program, at the University of Southern California, will lead a team to expand the role of two programs she created, Derm RISES, which targets inner city students, and Dermmunity, a community-based program that provides dermatology education to underserved communities in the Los Angeles area.
- Alex Ortega-Loayza, MD, associate professor of dermatology at Oregon Health & Science University and his team will partner with the Oregon Rural Practice-based Research Network to implement their teledermatology program at five clinics that serve different portions of rural and underserved communities across Oregon.
- Jules Lipoff, MD, clinical associate professor of dermatology, Temple University, Philadelphia, will lead a pilot program to establish a telemedicine dermatology clinic with Philadelphia FIGHT, a federally qualified health center in downtown Philadelphia where many patients lack high-speed Internet, and patients will be allowed direct access to telemedicine dermatology appointments within the primary care facility. The clinic’s patient population includes patients living with HIV, people who identify as LGBTQ+ and those who identify as trans or with a gender not matching their sex assigned at birth.
All four projects will complete postassessment surveys and quality assessment initiatives.
The GW clinic is ongoing, with plans for expansion and the establishment of additional programs with community partners in the Washington area, Dr. Friedman said in an interview.
“While these partnerships are in their infancy, I have high hopes that we will be able to impact even more individuals afflicted with dermatologic diseases and gain more insights into best practices for community engagement,” he added. “Many individuals who have come through our free clinic have followed up, by telehealth and/or in person at GW, depending on the clinical need to maintain continuity of care. In numerous cases, my impression is that this first point of contact is the key to ongoing treatment success, because it enables the access that may have been missing and engenders trust and confidence.”
, according to a press release from the university.
Four institutions will receive grants to implement the George Washington University model, which involved partnering with a local organization to provide an entry point for individuals in areas with limited access to medical care, with support from Pfizer Global Medical Grants.
“Targeting those who lack access to quality-based care for inflammatory dermatologic conditions, including atopic dermatitis (AD) and others, the grants will reach communities in Miami-Dade County, Fla., Los Angeles County, Calif., rural communities in Oregon, and downtown Philadelphia,” according to the announcement. GW’s Teledermatology Free Clinic was conceived in the wake of the COVID-19 pandemic, which further highlighted disparities in access to dermatologic care, Adam Friedman, M.D., professor and chair of dermatology at George Washington University, said in the press release.
GW implemented its clinic for residents in underserved areas of Washington, D.C., in partnership with the Rodham Institute and the Temple of Praise Church. “We set up a free clinic at the church through which patients were integrated into the GW medical records system, provided instruction on telemedicine best practices, exposed to comprehensive education about AD and underwent a free telemedicine visit with a member of the department of dermatology,” Dr. Friedman explained.
Most participants – 70% – did not have a dermatologist, 94% were extremely satisfied with the experience, and 90% reported that the clinic had a significant impact on the management of their AD, according to the results of a recently published postengagement survey.
The following are the recipients of the “Quality Improvement Initiative: Bridging the Inflammatory Dermatosis Care Divide with Teledermatology Grant Program”:
- Scott Elman, MD, assistant professor of clinical dermatology and medical director of outpatient dermatology at the University of Miami and his team will create a clinic in partnership with Lotus House, a resource center and residential facility serving homeless women and infants, with focus on interventions in both English and Spanish.
- Nada Elbuluk, MD, associate professor of clinical dermatology and director of the Skin of Color and Pigmentary Disorders Program, at the University of Southern California, will lead a team to expand the role of two programs she created, Derm RISES, which targets inner city students, and Dermmunity, a community-based program that provides dermatology education to underserved communities in the Los Angeles area.
- Alex Ortega-Loayza, MD, associate professor of dermatology at Oregon Health & Science University and his team will partner with the Oregon Rural Practice-based Research Network to implement their teledermatology program at five clinics that serve different portions of rural and underserved communities across Oregon.
- Jules Lipoff, MD, clinical associate professor of dermatology, Temple University, Philadelphia, will lead a pilot program to establish a telemedicine dermatology clinic with Philadelphia FIGHT, a federally qualified health center in downtown Philadelphia where many patients lack high-speed Internet, and patients will be allowed direct access to telemedicine dermatology appointments within the primary care facility. The clinic’s patient population includes patients living with HIV, people who identify as LGBTQ+ and those who identify as trans or with a gender not matching their sex assigned at birth.
All four projects will complete postassessment surveys and quality assessment initiatives.
The GW clinic is ongoing, with plans for expansion and the establishment of additional programs with community partners in the Washington area, Dr. Friedman said in an interview.
“While these partnerships are in their infancy, I have high hopes that we will be able to impact even more individuals afflicted with dermatologic diseases and gain more insights into best practices for community engagement,” he added. “Many individuals who have come through our free clinic have followed up, by telehealth and/or in person at GW, depending on the clinical need to maintain continuity of care. In numerous cases, my impression is that this first point of contact is the key to ongoing treatment success, because it enables the access that may have been missing and engenders trust and confidence.”
, according to a press release from the university.
Four institutions will receive grants to implement the George Washington University model, which involved partnering with a local organization to provide an entry point for individuals in areas with limited access to medical care, with support from Pfizer Global Medical Grants.
“Targeting those who lack access to quality-based care for inflammatory dermatologic conditions, including atopic dermatitis (AD) and others, the grants will reach communities in Miami-Dade County, Fla., Los Angeles County, Calif., rural communities in Oregon, and downtown Philadelphia,” according to the announcement. GW’s Teledermatology Free Clinic was conceived in the wake of the COVID-19 pandemic, which further highlighted disparities in access to dermatologic care, Adam Friedman, M.D., professor and chair of dermatology at George Washington University, said in the press release.
GW implemented its clinic for residents in underserved areas of Washington, D.C., in partnership with the Rodham Institute and the Temple of Praise Church. “We set up a free clinic at the church through which patients were integrated into the GW medical records system, provided instruction on telemedicine best practices, exposed to comprehensive education about AD and underwent a free telemedicine visit with a member of the department of dermatology,” Dr. Friedman explained.
Most participants – 70% – did not have a dermatologist, 94% were extremely satisfied with the experience, and 90% reported that the clinic had a significant impact on the management of their AD, according to the results of a recently published postengagement survey.
The following are the recipients of the “Quality Improvement Initiative: Bridging the Inflammatory Dermatosis Care Divide with Teledermatology Grant Program”:
- Scott Elman, MD, assistant professor of clinical dermatology and medical director of outpatient dermatology at the University of Miami and his team will create a clinic in partnership with Lotus House, a resource center and residential facility serving homeless women and infants, with focus on interventions in both English and Spanish.
- Nada Elbuluk, MD, associate professor of clinical dermatology and director of the Skin of Color and Pigmentary Disorders Program, at the University of Southern California, will lead a team to expand the role of two programs she created, Derm RISES, which targets inner city students, and Dermmunity, a community-based program that provides dermatology education to underserved communities in the Los Angeles area.
- Alex Ortega-Loayza, MD, associate professor of dermatology at Oregon Health & Science University and his team will partner with the Oregon Rural Practice-based Research Network to implement their teledermatology program at five clinics that serve different portions of rural and underserved communities across Oregon.
- Jules Lipoff, MD, clinical associate professor of dermatology, Temple University, Philadelphia, will lead a pilot program to establish a telemedicine dermatology clinic with Philadelphia FIGHT, a federally qualified health center in downtown Philadelphia where many patients lack high-speed Internet, and patients will be allowed direct access to telemedicine dermatology appointments within the primary care facility. The clinic’s patient population includes patients living with HIV, people who identify as LGBTQ+ and those who identify as trans or with a gender not matching their sex assigned at birth.
All four projects will complete postassessment surveys and quality assessment initiatives.
The GW clinic is ongoing, with plans for expansion and the establishment of additional programs with community partners in the Washington area, Dr. Friedman said in an interview.
“While these partnerships are in their infancy, I have high hopes that we will be able to impact even more individuals afflicted with dermatologic diseases and gain more insights into best practices for community engagement,” he added. “Many individuals who have come through our free clinic have followed up, by telehealth and/or in person at GW, depending on the clinical need to maintain continuity of care. In numerous cases, my impression is that this first point of contact is the key to ongoing treatment success, because it enables the access that may have been missing and engenders trust and confidence.”