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How Does Moderate to Severe Eczema Affect Growth in Children?
FROM AAD 2024
SAN DIEGO — , results from an ongoing 10-year observational study showed.
“We need to sort out whether this is reversed by newer treatments, especially in the 6- to 11-year-olds, as well as the factors that underlie it in atopic dermatitis,” said the study’s first author Amy S. Paller, MD, chair of dermatology, Northwestern University, Chicago, Illinois, following the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
Atopic Dermatitis Impacts Growth
In the ongoing international study called PEDISTAD, researchers enrolled 1326 children younger than 12 years with moderate to severe atopic dermatitis inadequately controlled by topical therapies who were candidates to receive systemic medications. They assessed the percentage of patients above the 50th percentile and the mean percentiles for height, weight, and body mass index (BMI) at baseline against the Centers for Disease Control and Prevention’s (CDC’s) Learning Management System reference healthy population, by age in months, and compared results to the CDC’s standardized growth curves for healthy children aged 0-12 years.
The investigators found that at baseline, compared with the age-specific population norms, 50% of men and 51% of women in the PEDISTAD study were above the 50th percentile for weight, but only 38% and 52%, respectively, were above the 50th percentile for height. Among patients aged 5-12 years, only 28% of men and 47% of women were above the 50th percentile for height, while 69% of men and 71% of women were above the 50th percentile for BMI.
Dr. Paller said that she was “not really surprised by the reduction in linear growth, since there are so many factors that may contribute,” including chronic inflammation, poor sleep, and the use of topical and systemic steroids. “But [it’s] good to have this data as an opportunity to see if our improved therapies can reverse this.”
She said that she was “a bit surprised by the increase in weight and body mass index, but this could reflect less physical activity/sports [participation and] deserves more investigation,” and added that the findings “mesh nicely with new attention on bone growth with good control of atopic dermatitis in this age group.”
Dr. Paller acknowledged certain limitations of the study, including the fact that those enrolled are a heterogeneous cohort with variable treatment regimens.
Some Answers, More Questions
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, who was asked to comment on the findings, said that atopic dermatitis “should be considered the cutaneous manifestations of a systemic inflammatory disease, though even if it were not, the impact on daily and nightly activities [such as sleep] could indirectly have systemic medical consequences.”
The data presented “highlights that children with moderate to severe disease have higher BMIs and shorter height than matched counterparts, likely owing to the treasure trove of direct and indirect consequences of uncontrolled type 2 inflammation,” he said. “What I would like to know, and as the authors astutely noted, could treatment, and especially early intervention, prevent or even alter this impact?”
Dr. Paller disclosed that she is a consultant for several pharmaceutical companies, including Sanofi and Regeneron, the study sponsor. She is also an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, LEO Pharma, and UCB and is a member of the data monitoring safety board for AbbVie, Abeona, Catawba, Galderma, and InMed. Dr. Friedman, who was not involved with the study, had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAD 2024
SAN DIEGO — , results from an ongoing 10-year observational study showed.
“We need to sort out whether this is reversed by newer treatments, especially in the 6- to 11-year-olds, as well as the factors that underlie it in atopic dermatitis,” said the study’s first author Amy S. Paller, MD, chair of dermatology, Northwestern University, Chicago, Illinois, following the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
Atopic Dermatitis Impacts Growth
In the ongoing international study called PEDISTAD, researchers enrolled 1326 children younger than 12 years with moderate to severe atopic dermatitis inadequately controlled by topical therapies who were candidates to receive systemic medications. They assessed the percentage of patients above the 50th percentile and the mean percentiles for height, weight, and body mass index (BMI) at baseline against the Centers for Disease Control and Prevention’s (CDC’s) Learning Management System reference healthy population, by age in months, and compared results to the CDC’s standardized growth curves for healthy children aged 0-12 years.
The investigators found that at baseline, compared with the age-specific population norms, 50% of men and 51% of women in the PEDISTAD study were above the 50th percentile for weight, but only 38% and 52%, respectively, were above the 50th percentile for height. Among patients aged 5-12 years, only 28% of men and 47% of women were above the 50th percentile for height, while 69% of men and 71% of women were above the 50th percentile for BMI.
Dr. Paller said that she was “not really surprised by the reduction in linear growth, since there are so many factors that may contribute,” including chronic inflammation, poor sleep, and the use of topical and systemic steroids. “But [it’s] good to have this data as an opportunity to see if our improved therapies can reverse this.”
She said that she was “a bit surprised by the increase in weight and body mass index, but this could reflect less physical activity/sports [participation and] deserves more investigation,” and added that the findings “mesh nicely with new attention on bone growth with good control of atopic dermatitis in this age group.”
Dr. Paller acknowledged certain limitations of the study, including the fact that those enrolled are a heterogeneous cohort with variable treatment regimens.
Some Answers, More Questions
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, who was asked to comment on the findings, said that atopic dermatitis “should be considered the cutaneous manifestations of a systemic inflammatory disease, though even if it were not, the impact on daily and nightly activities [such as sleep] could indirectly have systemic medical consequences.”
The data presented “highlights that children with moderate to severe disease have higher BMIs and shorter height than matched counterparts, likely owing to the treasure trove of direct and indirect consequences of uncontrolled type 2 inflammation,” he said. “What I would like to know, and as the authors astutely noted, could treatment, and especially early intervention, prevent or even alter this impact?”
Dr. Paller disclosed that she is a consultant for several pharmaceutical companies, including Sanofi and Regeneron, the study sponsor. She is also an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, LEO Pharma, and UCB and is a member of the data monitoring safety board for AbbVie, Abeona, Catawba, Galderma, and InMed. Dr. Friedman, who was not involved with the study, had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAD 2024
SAN DIEGO — , results from an ongoing 10-year observational study showed.
“We need to sort out whether this is reversed by newer treatments, especially in the 6- to 11-year-olds, as well as the factors that underlie it in atopic dermatitis,” said the study’s first author Amy S. Paller, MD, chair of dermatology, Northwestern University, Chicago, Illinois, following the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
Atopic Dermatitis Impacts Growth
In the ongoing international study called PEDISTAD, researchers enrolled 1326 children younger than 12 years with moderate to severe atopic dermatitis inadequately controlled by topical therapies who were candidates to receive systemic medications. They assessed the percentage of patients above the 50th percentile and the mean percentiles for height, weight, and body mass index (BMI) at baseline against the Centers for Disease Control and Prevention’s (CDC’s) Learning Management System reference healthy population, by age in months, and compared results to the CDC’s standardized growth curves for healthy children aged 0-12 years.
The investigators found that at baseline, compared with the age-specific population norms, 50% of men and 51% of women in the PEDISTAD study were above the 50th percentile for weight, but only 38% and 52%, respectively, were above the 50th percentile for height. Among patients aged 5-12 years, only 28% of men and 47% of women were above the 50th percentile for height, while 69% of men and 71% of women were above the 50th percentile for BMI.
Dr. Paller said that she was “not really surprised by the reduction in linear growth, since there are so many factors that may contribute,” including chronic inflammation, poor sleep, and the use of topical and systemic steroids. “But [it’s] good to have this data as an opportunity to see if our improved therapies can reverse this.”
She said that she was “a bit surprised by the increase in weight and body mass index, but this could reflect less physical activity/sports [participation and] deserves more investigation,” and added that the findings “mesh nicely with new attention on bone growth with good control of atopic dermatitis in this age group.”
Dr. Paller acknowledged certain limitations of the study, including the fact that those enrolled are a heterogeneous cohort with variable treatment regimens.
Some Answers, More Questions
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, who was asked to comment on the findings, said that atopic dermatitis “should be considered the cutaneous manifestations of a systemic inflammatory disease, though even if it were not, the impact on daily and nightly activities [such as sleep] could indirectly have systemic medical consequences.”
The data presented “highlights that children with moderate to severe disease have higher BMIs and shorter height than matched counterparts, likely owing to the treasure trove of direct and indirect consequences of uncontrolled type 2 inflammation,” he said. “What I would like to know, and as the authors astutely noted, could treatment, and especially early intervention, prevent or even alter this impact?”
Dr. Paller disclosed that she is a consultant for several pharmaceutical companies, including Sanofi and Regeneron, the study sponsor. She is also an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, LEO Pharma, and UCB and is a member of the data monitoring safety board for AbbVie, Abeona, Catawba, Galderma, and InMed. Dr. Friedman, who was not involved with the study, had no relevant disclosures.
A version of this article appeared on Medscape.com.
What’s ‘Tried and True’ in Atopic Dermatitis? An Expert Reflects
SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.
“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”
Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:
Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.
As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”
Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”
He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.
Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”
Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.
Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”
Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”
Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.
SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.
“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”
Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:
Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.
As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”
Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”
He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.
Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”
Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.
Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”
Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”
Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.
SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.
“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”
Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:
Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.
As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”
Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”
He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.
Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”
Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.
Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”
Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”
Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.
Childhood Atopic Dermatitis Linked to IBD Risk
TOPLINE:
, but atopic manifestations are generally not associated with IBD.
METHODOLOGY:
- Studies examining the link between atopy and IBD have yielded inconsistent results. Many of these studies included adults, introducing recall bias, or relied on physician diagnoses that might have overlooked mild cases.
- Researchers analyzed prospectively collected data on 83,311 children from two cohort studies, ABIS (1997-1999) and MoBa (1999-2008), who were followed up from birth until 2021 or a diagnosis of IBD.
- Information on parents was collected prospectively via questionnaires on any atopy their children might have developed by the age of 3 years. Atopy included conditions such as AD, asthma, food allergy, or allergic rhinitis.
TAKEAWAY:
- A total of 301 participants were diagnosed with IBD over 1,174,756 person-years of follow-up. By the age of 3 years, 31,671 children (38%) were reported to have any atopic manifestation.
- Children with AD at the age of 3 years demonstrated a significantly higher risk for IBD (pooled adjusted hazard ratio [aHR], 1.46), Crohn’s disease (pooled aHR, 1.53), and ulcerative colitis (pooled aHR, 1.78).
- Any atopic manifestation by the age of 3 years was not associated with a subsequent risk for IBD, Crohn’s disease, or ulcerative colitis, nor were analyses focused on early-life food-related allergy, asthma, and allergic rhinitis.
IN PRACTICE:
According to the authors, these findings suggested potential shared underlying causes between AD and IBD, which could help identify individuals at risk, and “a deeper understanding could significantly benefit the development of novel treatment approaches capable of effectively addressing both conditions, consequently enhancing patient outcomes.”
SOURCE:
This study, led by Tereza Lerchova, MD, PhD, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, was published online in The Journal of Pediatrics.
LIMITATIONS:
The findings of this study were mostly related to childhood-onset IBD instead of IBD in adult life. Lower participation in the MoBa study could limit generalizability to a broader population. In addition, there might have been lower participation from families without atopic manifestations.
DISCLOSURES:
The study was funded by the Swedish Society for Medical Research, Swedish Research Council, and ALF and supported by grants from the Swedish Child Diabetes Foundation, Swedish Council for Working Life and Social Research, Swedish Research Council, Medical Research Council of Southeast Sweden, JDRF Wallenberg Foundation, Linkoping University, and Joanna Cocozza Foundation. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
, but atopic manifestations are generally not associated with IBD.
METHODOLOGY:
- Studies examining the link between atopy and IBD have yielded inconsistent results. Many of these studies included adults, introducing recall bias, or relied on physician diagnoses that might have overlooked mild cases.
- Researchers analyzed prospectively collected data on 83,311 children from two cohort studies, ABIS (1997-1999) and MoBa (1999-2008), who were followed up from birth until 2021 or a diagnosis of IBD.
- Information on parents was collected prospectively via questionnaires on any atopy their children might have developed by the age of 3 years. Atopy included conditions such as AD, asthma, food allergy, or allergic rhinitis.
TAKEAWAY:
- A total of 301 participants were diagnosed with IBD over 1,174,756 person-years of follow-up. By the age of 3 years, 31,671 children (38%) were reported to have any atopic manifestation.
- Children with AD at the age of 3 years demonstrated a significantly higher risk for IBD (pooled adjusted hazard ratio [aHR], 1.46), Crohn’s disease (pooled aHR, 1.53), and ulcerative colitis (pooled aHR, 1.78).
- Any atopic manifestation by the age of 3 years was not associated with a subsequent risk for IBD, Crohn’s disease, or ulcerative colitis, nor were analyses focused on early-life food-related allergy, asthma, and allergic rhinitis.
IN PRACTICE:
According to the authors, these findings suggested potential shared underlying causes between AD and IBD, which could help identify individuals at risk, and “a deeper understanding could significantly benefit the development of novel treatment approaches capable of effectively addressing both conditions, consequently enhancing patient outcomes.”
SOURCE:
This study, led by Tereza Lerchova, MD, PhD, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, was published online in The Journal of Pediatrics.
LIMITATIONS:
The findings of this study were mostly related to childhood-onset IBD instead of IBD in adult life. Lower participation in the MoBa study could limit generalizability to a broader population. In addition, there might have been lower participation from families without atopic manifestations.
DISCLOSURES:
The study was funded by the Swedish Society for Medical Research, Swedish Research Council, and ALF and supported by grants from the Swedish Child Diabetes Foundation, Swedish Council for Working Life and Social Research, Swedish Research Council, Medical Research Council of Southeast Sweden, JDRF Wallenberg Foundation, Linkoping University, and Joanna Cocozza Foundation. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
, but atopic manifestations are generally not associated with IBD.
METHODOLOGY:
- Studies examining the link between atopy and IBD have yielded inconsistent results. Many of these studies included adults, introducing recall bias, or relied on physician diagnoses that might have overlooked mild cases.
- Researchers analyzed prospectively collected data on 83,311 children from two cohort studies, ABIS (1997-1999) and MoBa (1999-2008), who were followed up from birth until 2021 or a diagnosis of IBD.
- Information on parents was collected prospectively via questionnaires on any atopy their children might have developed by the age of 3 years. Atopy included conditions such as AD, asthma, food allergy, or allergic rhinitis.
TAKEAWAY:
- A total of 301 participants were diagnosed with IBD over 1,174,756 person-years of follow-up. By the age of 3 years, 31,671 children (38%) were reported to have any atopic manifestation.
- Children with AD at the age of 3 years demonstrated a significantly higher risk for IBD (pooled adjusted hazard ratio [aHR], 1.46), Crohn’s disease (pooled aHR, 1.53), and ulcerative colitis (pooled aHR, 1.78).
- Any atopic manifestation by the age of 3 years was not associated with a subsequent risk for IBD, Crohn’s disease, or ulcerative colitis, nor were analyses focused on early-life food-related allergy, asthma, and allergic rhinitis.
IN PRACTICE:
According to the authors, these findings suggested potential shared underlying causes between AD and IBD, which could help identify individuals at risk, and “a deeper understanding could significantly benefit the development of novel treatment approaches capable of effectively addressing both conditions, consequently enhancing patient outcomes.”
SOURCE:
This study, led by Tereza Lerchova, MD, PhD, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, was published online in The Journal of Pediatrics.
LIMITATIONS:
The findings of this study were mostly related to childhood-onset IBD instead of IBD in adult life. Lower participation in the MoBa study could limit generalizability to a broader population. In addition, there might have been lower participation from families without atopic manifestations.
DISCLOSURES:
The study was funded by the Swedish Society for Medical Research, Swedish Research Council, and ALF and supported by grants from the Swedish Child Diabetes Foundation, Swedish Council for Working Life and Social Research, Swedish Research Council, Medical Research Council of Southeast Sweden, JDRF Wallenberg Foundation, Linkoping University, and Joanna Cocozza Foundation. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Commentary: Choosing Treatments of AD, and Possible Connection to Learning Issues, April 2024
Not everyone with AD treated with dupilumab gets clear or almost clear in clinical trials. The study by Cork and colleagues looked to see whether those patients who did not get to clear or almost clear were still having clinically meaningful improvement. To test this, the investigators looked at patients who still had mild or worse disease and then at the proportion of those patients at week 16 who achieved a composite endpoint encompassing clinically meaningful changes in AD signs, symptoms, and quality of life: ≥50% improvement in Eczema Area and Severity Index or ≥4-point reduction in worst scratch/itch numerical rating scale, or ≥6-point reduction in Children's Dermatology Life Quality Index/Infants' Dermatitis Quality of Life Index. Significantly more patients, both clinically and statistically significantly more, receiving dupilumab vs placebo achieved the composite endpoint (77.7% vs 24.6%; P < .0001).
The "success rate" reported in clinical trials underestimates how often patients can be successfully treated with dupilumab. I don't need a complicated composite outcome to know this. I just use the standardized 2-point Patient Global Assessment measure. I ask patients, "How are you doing?" If they say "Great," that's success. If they say, "Not so good," that's failure. I think about 80% of patients with AD treated with dupilumab have success based on this standard.
Hand dermatitis can be quite resistant to treatment. Even making a diagnosis can be challenging, as psoriasis and dermatitis of the hands looks so similar to me (and when I used to send biopsies and ask the pathologist whether it's dermatitis or psoriasis, invariably the dermatopathologist responded "yes"). The study by Kamphuis and colleagues examined the efficacy of abrocitinib in just over 100 patients with hand eczema who were enrolled in the BioDay registry. Such registries are very helpful for assessing real-world results. The drug seemed reasonably successful, with only about 30% discontinuing treatment. About two thirds of the discontinuations were due to inefficacy and about one third to an adverse event.
I think there's real value in prescribing the treatments patients want. Studies like the one by Ameen and colleagues, using a discrete-choice methodology, allows one to determine patients' average preferences. In this study, the discrete-choice approach found that patients prefer safety over other attributes. Some years ago, my colleagues and I queried patients to get a sense of their quantitative preferences for different treatments. Our study also found that patients preferred safety over other attributes. However, when we asked them to choose among different treatment options, they didn't choose the safest one. I think they believe that they prefer safety, but I'm not sure they really do. In any case, the average preference of the entire population of people with AD isn't really all that important when we've got just one patient sitting in front of us. It's that particular patient's preference that should drive the treatment plan.
Not everyone with AD treated with dupilumab gets clear or almost clear in clinical trials. The study by Cork and colleagues looked to see whether those patients who did not get to clear or almost clear were still having clinically meaningful improvement. To test this, the investigators looked at patients who still had mild or worse disease and then at the proportion of those patients at week 16 who achieved a composite endpoint encompassing clinically meaningful changes in AD signs, symptoms, and quality of life: ≥50% improvement in Eczema Area and Severity Index or ≥4-point reduction in worst scratch/itch numerical rating scale, or ≥6-point reduction in Children's Dermatology Life Quality Index/Infants' Dermatitis Quality of Life Index. Significantly more patients, both clinically and statistically significantly more, receiving dupilumab vs placebo achieved the composite endpoint (77.7% vs 24.6%; P < .0001).
The "success rate" reported in clinical trials underestimates how often patients can be successfully treated with dupilumab. I don't need a complicated composite outcome to know this. I just use the standardized 2-point Patient Global Assessment measure. I ask patients, "How are you doing?" If they say "Great," that's success. If they say, "Not so good," that's failure. I think about 80% of patients with AD treated with dupilumab have success based on this standard.
Hand dermatitis can be quite resistant to treatment. Even making a diagnosis can be challenging, as psoriasis and dermatitis of the hands looks so similar to me (and when I used to send biopsies and ask the pathologist whether it's dermatitis or psoriasis, invariably the dermatopathologist responded "yes"). The study by Kamphuis and colleagues examined the efficacy of abrocitinib in just over 100 patients with hand eczema who were enrolled in the BioDay registry. Such registries are very helpful for assessing real-world results. The drug seemed reasonably successful, with only about 30% discontinuing treatment. About two thirds of the discontinuations were due to inefficacy and about one third to an adverse event.
I think there's real value in prescribing the treatments patients want. Studies like the one by Ameen and colleagues, using a discrete-choice methodology, allows one to determine patients' average preferences. In this study, the discrete-choice approach found that patients prefer safety over other attributes. Some years ago, my colleagues and I queried patients to get a sense of their quantitative preferences for different treatments. Our study also found that patients preferred safety over other attributes. However, when we asked them to choose among different treatment options, they didn't choose the safest one. I think they believe that they prefer safety, but I'm not sure they really do. In any case, the average preference of the entire population of people with AD isn't really all that important when we've got just one patient sitting in front of us. It's that particular patient's preference that should drive the treatment plan.
Not everyone with AD treated with dupilumab gets clear or almost clear in clinical trials. The study by Cork and colleagues looked to see whether those patients who did not get to clear or almost clear were still having clinically meaningful improvement. To test this, the investigators looked at patients who still had mild or worse disease and then at the proportion of those patients at week 16 who achieved a composite endpoint encompassing clinically meaningful changes in AD signs, symptoms, and quality of life: ≥50% improvement in Eczema Area and Severity Index or ≥4-point reduction in worst scratch/itch numerical rating scale, or ≥6-point reduction in Children's Dermatology Life Quality Index/Infants' Dermatitis Quality of Life Index. Significantly more patients, both clinically and statistically significantly more, receiving dupilumab vs placebo achieved the composite endpoint (77.7% vs 24.6%; P < .0001).
The "success rate" reported in clinical trials underestimates how often patients can be successfully treated with dupilumab. I don't need a complicated composite outcome to know this. I just use the standardized 2-point Patient Global Assessment measure. I ask patients, "How are you doing?" If they say "Great," that's success. If they say, "Not so good," that's failure. I think about 80% of patients with AD treated with dupilumab have success based on this standard.
Hand dermatitis can be quite resistant to treatment. Even making a diagnosis can be challenging, as psoriasis and dermatitis of the hands looks so similar to me (and when I used to send biopsies and ask the pathologist whether it's dermatitis or psoriasis, invariably the dermatopathologist responded "yes"). The study by Kamphuis and colleagues examined the efficacy of abrocitinib in just over 100 patients with hand eczema who were enrolled in the BioDay registry. Such registries are very helpful for assessing real-world results. The drug seemed reasonably successful, with only about 30% discontinuing treatment. About two thirds of the discontinuations were due to inefficacy and about one third to an adverse event.
I think there's real value in prescribing the treatments patients want. Studies like the one by Ameen and colleagues, using a discrete-choice methodology, allows one to determine patients' average preferences. In this study, the discrete-choice approach found that patients prefer safety over other attributes. Some years ago, my colleagues and I queried patients to get a sense of their quantitative preferences for different treatments. Our study also found that patients preferred safety over other attributes. However, when we asked them to choose among different treatment options, they didn't choose the safest one. I think they believe that they prefer safety, but I'm not sure they really do. In any case, the average preference of the entire population of people with AD isn't really all that important when we've got just one patient sitting in front of us. It's that particular patient's preference that should drive the treatment plan.
Nemolizumab Efficacy for Prurigo Nodularis Persists at 1 Year
SAN DIEGO — in an open-label follow-up pivotal trial following patients out to 52 weeks.
The OLYMPIA 2 trial, published just a few months ago, was positive for the primary endpoint of itch, and the 52-week data show “on-going improvement” not just in this key symptom but in the resolution of skin lesions, according to Shawn Kwatra, MD, director of the itch center and associate professor of dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland.
The drug, which was found well tolerated in the double-blind OLYMPIA 2 study at 16 weeks, has not been associated with any new adverse events (AEs) in follow-up so far, according to Dr. Kwatra, who presented these findings in a late-breaker session at the annual meeting of the American Academy of Dermatology (AAD).
The promise of an anti-IL-31 drug for sustained control of itch and inflammation was further supported by a separate late breaker on long-term maintenance data on nemolizumab for moderate to severe atopic dermatitis (AD).
New Prurigo Nodularis Therapies Needed
For prurigo nodularis, excitement about a new therapy is particularly warranted, according to Dr. Kwatra. Current treatment options, such as steroids and antihistamines, are neither well-tolerated nor particularly effective in most patients. He indicated that the very positive interim 52-week data from the ongoing open-label extension suggests that nemolizumab might be an important step forward for patients with this disease.
The interim 52-week analysis included 307 patients on continuous nemolizumab and 174 patients randomized previously to placebo and were nemolizumab-naive when they entered the open-label extension. Participants were drawn from the phase 3 trial as well as an earlier phase 2 study. Nemolizumab in all patients was delivered at a subcutaneous dose of 45 mg every 4 weeks.
Pointing out that the 2024 AAD annual meeting, with more than 19,000 attendees, “was the largest dermatology conference in the history of the world,” he added that his late-breaker results represent “the largest prurigo nodularis clinical study in the history of the world.”
At 52 weeks, 89.9% and 83.3% of those on continuous nemolizumab and those switched to nemolizumab, respectively, had achieved at least a 4-point reduction from baseline on the Peak Pruritus Numerical Rating Scale (NRS), which has a range from 0 to 10.
Approximately two thirds of patients (67.8% and 64.4%, respectively) had a weekly average peak NRS of ≤ 2, meaning they were free or almost free of itch. The improvement in a sleep index and in quality of life as measured with the Dermatology Life Quality Index closely followed the relief of itch with the large gains achieved within weeks of initiating treatment continuing on an upward slope at 52 weeks.
Over this time, lesions were also resolving. By week 52, healing of more than 75% of lesions had been achieved by 79.1% in both those on continuous nemolizumab and those who had been switched to nemolizumab. The rate of response was again about two thirds for those with lesion resolution considered clear or almost clear by the Investigator’s Global Assessment (IGA) response.
No Serious AEs Over Extended Follow-Up
With a mean duration of 388 days follow-up, there were no serious AEs that were clearly treatment related, but Dr. Kwatra did report that some patients developed mild eczematous lesions that typically responded to topical therapy. He also reported that asthma, particularly worsening asthma in patients already diagnosed with this disease, was seen in a small proportion of patients. Both were considered manageable, and no patients discontinued therapy because of these events, Dr. Kwatra said.
While further follow-up is planned, “we have never seen data in a prurigo nodularis [treatment trial] past 6 months,” he pointed out. For a challenging disease with a major adverse effect on quality of life, nemolizumab, if approved, will offer an important option for a difficult disease, he added.
Itch Improves in Patients with AD
Further support for the long-term safety of nemolizumab and its efficacy against itch was provided by another phase 3 extension study conducted in the treatment of AD. These long-term extension results were also presented in a late breaker session at the AAD meeting.
Evaluating maintenance data from responders, defined as a 75% reduction lesions on the Eczema Area and Severity Index (EASI-75) or as clear or almost clear skin on IGA at the end of the randomized ARCADIA 1 and 2 trials, there were 169 patients on every 4-week nemolizumab, 169 patients on every 8-week nemolizumab, and 169 patients on every 4-week placebo.
For pruritus, a ≥ 4 point NRS reduction was achieved at week 48 in 76.2% of those on the every 4-week dose, 59.7% of those on the every 8-week dose, and 41% on those on placebo, reported Jonathan Silverberg, MD, PhD, director of clinical research, Department of Dermatology, George Washington School of Medicine, Washington.
These not only represented sustained responses over the course of 48 weeks, but there was a gradual rise in this rate of success from baseline in the higher dose group. For a NRS score of ≤ 2, meaning no itch or almost no itch, the proportions were 64.9%, 52.9%, and 31.3%, respectively. These were accompanied by sustained responses in IGA and EASI-75 scores.
Overall, there was a “nice durability of response” over the maintenance period, with no new or dose-related safety signals, according to Dr. Silverberg. He pointed out that the every 8-week dose response was lower than every 4-week dose response, but “it looks very good” in regard to response and duration of response, “suggesting that this might be an option for a large subset of patients.”
Andrew Blauvelt, MD, an investigator with Oregon Medical Research Center, Portland, Oregon, cautioned that despite the promise, dermatologists “might need help” in understanding this new agent and using it appropriately. He pointed out that it employs a new mechanism of action, and it has “a couple of new twists that we have not seen with other drugs,” including its association with worsening asthma.
Noting that asthma exacerbation has been reported in a proportion of treated patients approaching 4%, he expressed concern “that this is not rare.” He also expressed concern about reports of peripheral edema and asked Dr. Kwatra specifically how this should be handled in the routine clinical setting.
Pointing out that the 1% of new cases of asthma in the nemolizumab arm was, in fact, lower than the rate of new cases in the placebo arm, Dr. Kwatra said that there have been cases of increased asthma symptoms in patients with existing disease. However, he added that this and the reports of peripheral edema, some of which appear to be simply associated with prurigo nodularis, typically resolve with routine interventions. He said, however, that these side effects represent legitimate concerns that clinicians should consider, but he indicated that they do not appear to be a threat to the benefit-to-risk ratio of this agent.
In February 2024, the Food and Drug Administration and the European Medicines Agency accepted submissions for nemolizumab for the treatment of prurigo nodularis and AD, according to Galderma, the company developing nemolizumab.
Dr. Kwatra reported a financial relationship with more than 15 pharmaceutical companies, including Galderma, which sponsored the nemolizumab trials. Dr. Silverberg reported financial relationships with more than 35 pharmaceutical companies, including Galderma. Dr. Blauvelt reported financial relationships with more than 20 pharmaceutical companies, including Galderma.
A version of this article appeared on Medscape.com.
SAN DIEGO — in an open-label follow-up pivotal trial following patients out to 52 weeks.
The OLYMPIA 2 trial, published just a few months ago, was positive for the primary endpoint of itch, and the 52-week data show “on-going improvement” not just in this key symptom but in the resolution of skin lesions, according to Shawn Kwatra, MD, director of the itch center and associate professor of dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland.
The drug, which was found well tolerated in the double-blind OLYMPIA 2 study at 16 weeks, has not been associated with any new adverse events (AEs) in follow-up so far, according to Dr. Kwatra, who presented these findings in a late-breaker session at the annual meeting of the American Academy of Dermatology (AAD).
The promise of an anti-IL-31 drug for sustained control of itch and inflammation was further supported by a separate late breaker on long-term maintenance data on nemolizumab for moderate to severe atopic dermatitis (AD).
New Prurigo Nodularis Therapies Needed
For prurigo nodularis, excitement about a new therapy is particularly warranted, according to Dr. Kwatra. Current treatment options, such as steroids and antihistamines, are neither well-tolerated nor particularly effective in most patients. He indicated that the very positive interim 52-week data from the ongoing open-label extension suggests that nemolizumab might be an important step forward for patients with this disease.
The interim 52-week analysis included 307 patients on continuous nemolizumab and 174 patients randomized previously to placebo and were nemolizumab-naive when they entered the open-label extension. Participants were drawn from the phase 3 trial as well as an earlier phase 2 study. Nemolizumab in all patients was delivered at a subcutaneous dose of 45 mg every 4 weeks.
Pointing out that the 2024 AAD annual meeting, with more than 19,000 attendees, “was the largest dermatology conference in the history of the world,” he added that his late-breaker results represent “the largest prurigo nodularis clinical study in the history of the world.”
At 52 weeks, 89.9% and 83.3% of those on continuous nemolizumab and those switched to nemolizumab, respectively, had achieved at least a 4-point reduction from baseline on the Peak Pruritus Numerical Rating Scale (NRS), which has a range from 0 to 10.
Approximately two thirds of patients (67.8% and 64.4%, respectively) had a weekly average peak NRS of ≤ 2, meaning they were free or almost free of itch. The improvement in a sleep index and in quality of life as measured with the Dermatology Life Quality Index closely followed the relief of itch with the large gains achieved within weeks of initiating treatment continuing on an upward slope at 52 weeks.
Over this time, lesions were also resolving. By week 52, healing of more than 75% of lesions had been achieved by 79.1% in both those on continuous nemolizumab and those who had been switched to nemolizumab. The rate of response was again about two thirds for those with lesion resolution considered clear or almost clear by the Investigator’s Global Assessment (IGA) response.
No Serious AEs Over Extended Follow-Up
With a mean duration of 388 days follow-up, there were no serious AEs that were clearly treatment related, but Dr. Kwatra did report that some patients developed mild eczematous lesions that typically responded to topical therapy. He also reported that asthma, particularly worsening asthma in patients already diagnosed with this disease, was seen in a small proportion of patients. Both were considered manageable, and no patients discontinued therapy because of these events, Dr. Kwatra said.
While further follow-up is planned, “we have never seen data in a prurigo nodularis [treatment trial] past 6 months,” he pointed out. For a challenging disease with a major adverse effect on quality of life, nemolizumab, if approved, will offer an important option for a difficult disease, he added.
Itch Improves in Patients with AD
Further support for the long-term safety of nemolizumab and its efficacy against itch was provided by another phase 3 extension study conducted in the treatment of AD. These long-term extension results were also presented in a late breaker session at the AAD meeting.
Evaluating maintenance data from responders, defined as a 75% reduction lesions on the Eczema Area and Severity Index (EASI-75) or as clear or almost clear skin on IGA at the end of the randomized ARCADIA 1 and 2 trials, there were 169 patients on every 4-week nemolizumab, 169 patients on every 8-week nemolizumab, and 169 patients on every 4-week placebo.
For pruritus, a ≥ 4 point NRS reduction was achieved at week 48 in 76.2% of those on the every 4-week dose, 59.7% of those on the every 8-week dose, and 41% on those on placebo, reported Jonathan Silverberg, MD, PhD, director of clinical research, Department of Dermatology, George Washington School of Medicine, Washington.
These not only represented sustained responses over the course of 48 weeks, but there was a gradual rise in this rate of success from baseline in the higher dose group. For a NRS score of ≤ 2, meaning no itch or almost no itch, the proportions were 64.9%, 52.9%, and 31.3%, respectively. These were accompanied by sustained responses in IGA and EASI-75 scores.
Overall, there was a “nice durability of response” over the maintenance period, with no new or dose-related safety signals, according to Dr. Silverberg. He pointed out that the every 8-week dose response was lower than every 4-week dose response, but “it looks very good” in regard to response and duration of response, “suggesting that this might be an option for a large subset of patients.”
Andrew Blauvelt, MD, an investigator with Oregon Medical Research Center, Portland, Oregon, cautioned that despite the promise, dermatologists “might need help” in understanding this new agent and using it appropriately. He pointed out that it employs a new mechanism of action, and it has “a couple of new twists that we have not seen with other drugs,” including its association with worsening asthma.
Noting that asthma exacerbation has been reported in a proportion of treated patients approaching 4%, he expressed concern “that this is not rare.” He also expressed concern about reports of peripheral edema and asked Dr. Kwatra specifically how this should be handled in the routine clinical setting.
Pointing out that the 1% of new cases of asthma in the nemolizumab arm was, in fact, lower than the rate of new cases in the placebo arm, Dr. Kwatra said that there have been cases of increased asthma symptoms in patients with existing disease. However, he added that this and the reports of peripheral edema, some of which appear to be simply associated with prurigo nodularis, typically resolve with routine interventions. He said, however, that these side effects represent legitimate concerns that clinicians should consider, but he indicated that they do not appear to be a threat to the benefit-to-risk ratio of this agent.
In February 2024, the Food and Drug Administration and the European Medicines Agency accepted submissions for nemolizumab for the treatment of prurigo nodularis and AD, according to Galderma, the company developing nemolizumab.
Dr. Kwatra reported a financial relationship with more than 15 pharmaceutical companies, including Galderma, which sponsored the nemolizumab trials. Dr. Silverberg reported financial relationships with more than 35 pharmaceutical companies, including Galderma. Dr. Blauvelt reported financial relationships with more than 20 pharmaceutical companies, including Galderma.
A version of this article appeared on Medscape.com.
SAN DIEGO — in an open-label follow-up pivotal trial following patients out to 52 weeks.
The OLYMPIA 2 trial, published just a few months ago, was positive for the primary endpoint of itch, and the 52-week data show “on-going improvement” not just in this key symptom but in the resolution of skin lesions, according to Shawn Kwatra, MD, director of the itch center and associate professor of dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland.
The drug, which was found well tolerated in the double-blind OLYMPIA 2 study at 16 weeks, has not been associated with any new adverse events (AEs) in follow-up so far, according to Dr. Kwatra, who presented these findings in a late-breaker session at the annual meeting of the American Academy of Dermatology (AAD).
The promise of an anti-IL-31 drug for sustained control of itch and inflammation was further supported by a separate late breaker on long-term maintenance data on nemolizumab for moderate to severe atopic dermatitis (AD).
New Prurigo Nodularis Therapies Needed
For prurigo nodularis, excitement about a new therapy is particularly warranted, according to Dr. Kwatra. Current treatment options, such as steroids and antihistamines, are neither well-tolerated nor particularly effective in most patients. He indicated that the very positive interim 52-week data from the ongoing open-label extension suggests that nemolizumab might be an important step forward for patients with this disease.
The interim 52-week analysis included 307 patients on continuous nemolizumab and 174 patients randomized previously to placebo and were nemolizumab-naive when they entered the open-label extension. Participants were drawn from the phase 3 trial as well as an earlier phase 2 study. Nemolizumab in all patients was delivered at a subcutaneous dose of 45 mg every 4 weeks.
Pointing out that the 2024 AAD annual meeting, with more than 19,000 attendees, “was the largest dermatology conference in the history of the world,” he added that his late-breaker results represent “the largest prurigo nodularis clinical study in the history of the world.”
At 52 weeks, 89.9% and 83.3% of those on continuous nemolizumab and those switched to nemolizumab, respectively, had achieved at least a 4-point reduction from baseline on the Peak Pruritus Numerical Rating Scale (NRS), which has a range from 0 to 10.
Approximately two thirds of patients (67.8% and 64.4%, respectively) had a weekly average peak NRS of ≤ 2, meaning they were free or almost free of itch. The improvement in a sleep index and in quality of life as measured with the Dermatology Life Quality Index closely followed the relief of itch with the large gains achieved within weeks of initiating treatment continuing on an upward slope at 52 weeks.
Over this time, lesions were also resolving. By week 52, healing of more than 75% of lesions had been achieved by 79.1% in both those on continuous nemolizumab and those who had been switched to nemolizumab. The rate of response was again about two thirds for those with lesion resolution considered clear or almost clear by the Investigator’s Global Assessment (IGA) response.
No Serious AEs Over Extended Follow-Up
With a mean duration of 388 days follow-up, there were no serious AEs that were clearly treatment related, but Dr. Kwatra did report that some patients developed mild eczematous lesions that typically responded to topical therapy. He also reported that asthma, particularly worsening asthma in patients already diagnosed with this disease, was seen in a small proportion of patients. Both were considered manageable, and no patients discontinued therapy because of these events, Dr. Kwatra said.
While further follow-up is planned, “we have never seen data in a prurigo nodularis [treatment trial] past 6 months,” he pointed out. For a challenging disease with a major adverse effect on quality of life, nemolizumab, if approved, will offer an important option for a difficult disease, he added.
Itch Improves in Patients with AD
Further support for the long-term safety of nemolizumab and its efficacy against itch was provided by another phase 3 extension study conducted in the treatment of AD. These long-term extension results were also presented in a late breaker session at the AAD meeting.
Evaluating maintenance data from responders, defined as a 75% reduction lesions on the Eczema Area and Severity Index (EASI-75) or as clear or almost clear skin on IGA at the end of the randomized ARCADIA 1 and 2 trials, there were 169 patients on every 4-week nemolizumab, 169 patients on every 8-week nemolizumab, and 169 patients on every 4-week placebo.
For pruritus, a ≥ 4 point NRS reduction was achieved at week 48 in 76.2% of those on the every 4-week dose, 59.7% of those on the every 8-week dose, and 41% on those on placebo, reported Jonathan Silverberg, MD, PhD, director of clinical research, Department of Dermatology, George Washington School of Medicine, Washington.
These not only represented sustained responses over the course of 48 weeks, but there was a gradual rise in this rate of success from baseline in the higher dose group. For a NRS score of ≤ 2, meaning no itch or almost no itch, the proportions were 64.9%, 52.9%, and 31.3%, respectively. These were accompanied by sustained responses in IGA and EASI-75 scores.
Overall, there was a “nice durability of response” over the maintenance period, with no new or dose-related safety signals, according to Dr. Silverberg. He pointed out that the every 8-week dose response was lower than every 4-week dose response, but “it looks very good” in regard to response and duration of response, “suggesting that this might be an option for a large subset of patients.”
Andrew Blauvelt, MD, an investigator with Oregon Medical Research Center, Portland, Oregon, cautioned that despite the promise, dermatologists “might need help” in understanding this new agent and using it appropriately. He pointed out that it employs a new mechanism of action, and it has “a couple of new twists that we have not seen with other drugs,” including its association with worsening asthma.
Noting that asthma exacerbation has been reported in a proportion of treated patients approaching 4%, he expressed concern “that this is not rare.” He also expressed concern about reports of peripheral edema and asked Dr. Kwatra specifically how this should be handled in the routine clinical setting.
Pointing out that the 1% of new cases of asthma in the nemolizumab arm was, in fact, lower than the rate of new cases in the placebo arm, Dr. Kwatra said that there have been cases of increased asthma symptoms in patients with existing disease. However, he added that this and the reports of peripheral edema, some of which appear to be simply associated with prurigo nodularis, typically resolve with routine interventions. He said, however, that these side effects represent legitimate concerns that clinicians should consider, but he indicated that they do not appear to be a threat to the benefit-to-risk ratio of this agent.
In February 2024, the Food and Drug Administration and the European Medicines Agency accepted submissions for nemolizumab for the treatment of prurigo nodularis and AD, according to Galderma, the company developing nemolizumab.
Dr. Kwatra reported a financial relationship with more than 15 pharmaceutical companies, including Galderma, which sponsored the nemolizumab trials. Dr. Silverberg reported financial relationships with more than 35 pharmaceutical companies, including Galderma. Dr. Blauvelt reported financial relationships with more than 20 pharmaceutical companies, including Galderma.
A version of this article appeared on Medscape.com.
FROM AAD 2024
Lebrikizumab Found Effective for Atopic Dermatitis in Patients With Darker Skin Tones
SAN DIEGO — , interim results from a novel phase 3b trial showed.
Lebrikizumab, a novel monoclonal antibody being developed by Eli Lilly and Co, binds with high affinity to interleukin (IL)–13, thereby blocking the downstream effects of IL-13 with high potency, one of the study investigators, Jill S. Waibel, MD, a dermatologist in Miami, said at the annual meeting of the American Academy of Dermatology. Though the efficacy and safety of lebrikizumab to treat moderate to severe AD have been established in phase 3 studies, including subset analyses by race and ethnicity, “there is a paucity of data to guide the treatment of moderate-to-severe AD in populations traditionally under-represented in clinical trials, including patients with skin of color,” she said.
During a late-breaking abstract session, Dr. Waibel presented interim 16-week results from ADmirable, a phase 3b, open-label, 24-week study, was the first study to evaluate the safety and efficacy of lebrikizumab in adult and adolescents with skin of color and moderate to severe AD. At baseline and at 2 weeks, patients received a 500-mg loading dose of lebrikizumab. Through week 16, they received a 250-mg dose every 2 weeks. The study’s primary endpoint was the proportion of patients who achieved a 75% reduction in EASI-75 at week 16. “If they achieved the primary endpoint at week 16, they went to a 250-mg dose every 4 weeks,” Dr. Waibel said. “If they did not achieve that [primary endpoint] they stayed on the 250-mg dose every 2 weeks.”
The analysis included 50 patients with skin types IV, V, and VI who self-reported their race as Black or African American, American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander. They had chronic AD for at least 1 year, moderate to severe disease at baseline, a history of an inadequate response to topical medications, and were naive to biologics indicated for the treatment of AD.
Week 16 outcomes of interest were the EASI, the Investigator’s Global Assessment (IGA) of 0 or 1, the Pruritus Numerical Rating Scale (NRS), and PDCA-Derm, a scale developed by Eli Lilly and Co that was used to compare postinflammatory lesions to unaffected adjacent normal skin. All data for statistical analyses were summarized as observed.
At baseline, the mean age of the 50 patients was 42 years, 46% were women, their mean body mass index was 30.2, and the mean age at AD onset was 23 years. Most study participants (80%) were Black or African American, 14% were Asian, and 6% were American Indian or Alaska Native; 78% were not Hispanic or Latino and 22% were Hispanic or Latino. The mean EASI score was 28.1, the mean body surface area affected was 41.7%, and the mean Pruritus NRS score was 7.2 out of 11. According to the PDCA-Derm scale, 18% of patients had hypopigmented lesions, and 54% had hyperpigmented lesions.
After 16 weeks of treatment, 68% of patients achieved an EASI-75 response, whereas 46% achieved an EASI-90 response, Dr. Waibel reported at the meeting. In addition, 39% of patients achieved an IGA score of 0 or 1, 56% achieved a ≥ 4-point improvement on the Pruritus NRS, and 66% achieved a ≥ 3-point improvement on the Pruritus NRS. The PDCA-Derm score identified improvement in postinflammatory hyperpigmented lesions in 12 of 21 patients and improvement to normal skin tone in six of 21 patients.
“I have a large population [with skin of color in my practice],” Dr. Waibel said. “I usually tell my [patients with postinflammatory hyperpigmentation] that it takes 6 months to see improvement. In this study, we saw patients achieve improvement in skin tone in a 4-month time frame. PIH is sometimes more distressing than a primary condition, whether it’s acne or atopic dermatitis. In this case, it was surprisingly improved with lebrikizumab.”
No new safety signals or serious adverse events were observed. “This is very exciting because it’s the first time there has been a trial focusing on [patients with skin of color] with moderate to severe eczema in skin types IV-VI,” Dr. Waibel said.
In an interview, the study’s lead investigator, Andrew Alexis, MD, MPH, vice chair for diversity and inclusion in the department of dermatology and professor of clinical dermatology at Weill Cornell Medicine, New York City, said that the interim results from this study “ add valuable, clinically relevant data on the treatment of moderate to severe AD in patient populations with skin of color.”
“An interesting finding,” he continued, “was that improvement in postinflammatory hyperpigmented lesions was seen in 12 of 21 patients and improvement to normal skin tone was observed in six of 21 patients at week 16. This is particularly relevant to patients with skin of color who frequently suffer from pigmentary changes in association with their AD.”
Lebrikizumab was approved in November 2023 in Europe for the treatment of moderate to severe AD in people aged 12 years or older and is currently under review by the Food and Drug Administration for treatment of AD.
Both Dr. Waibel and Dr. Alexis disclosed numerous conflicts of interest from various pharmaceutical companies, including serving as a consultant and/or advisor to Eli Lilly and Co.
A version of this article appeared on Medscape.com.
SAN DIEGO — , interim results from a novel phase 3b trial showed.
Lebrikizumab, a novel monoclonal antibody being developed by Eli Lilly and Co, binds with high affinity to interleukin (IL)–13, thereby blocking the downstream effects of IL-13 with high potency, one of the study investigators, Jill S. Waibel, MD, a dermatologist in Miami, said at the annual meeting of the American Academy of Dermatology. Though the efficacy and safety of lebrikizumab to treat moderate to severe AD have been established in phase 3 studies, including subset analyses by race and ethnicity, “there is a paucity of data to guide the treatment of moderate-to-severe AD in populations traditionally under-represented in clinical trials, including patients with skin of color,” she said.
During a late-breaking abstract session, Dr. Waibel presented interim 16-week results from ADmirable, a phase 3b, open-label, 24-week study, was the first study to evaluate the safety and efficacy of lebrikizumab in adult and adolescents with skin of color and moderate to severe AD. At baseline and at 2 weeks, patients received a 500-mg loading dose of lebrikizumab. Through week 16, they received a 250-mg dose every 2 weeks. The study’s primary endpoint was the proportion of patients who achieved a 75% reduction in EASI-75 at week 16. “If they achieved the primary endpoint at week 16, they went to a 250-mg dose every 4 weeks,” Dr. Waibel said. “If they did not achieve that [primary endpoint] they stayed on the 250-mg dose every 2 weeks.”
The analysis included 50 patients with skin types IV, V, and VI who self-reported their race as Black or African American, American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander. They had chronic AD for at least 1 year, moderate to severe disease at baseline, a history of an inadequate response to topical medications, and were naive to biologics indicated for the treatment of AD.
Week 16 outcomes of interest were the EASI, the Investigator’s Global Assessment (IGA) of 0 or 1, the Pruritus Numerical Rating Scale (NRS), and PDCA-Derm, a scale developed by Eli Lilly and Co that was used to compare postinflammatory lesions to unaffected adjacent normal skin. All data for statistical analyses were summarized as observed.
At baseline, the mean age of the 50 patients was 42 years, 46% were women, their mean body mass index was 30.2, and the mean age at AD onset was 23 years. Most study participants (80%) were Black or African American, 14% were Asian, and 6% were American Indian or Alaska Native; 78% were not Hispanic or Latino and 22% were Hispanic or Latino. The mean EASI score was 28.1, the mean body surface area affected was 41.7%, and the mean Pruritus NRS score was 7.2 out of 11. According to the PDCA-Derm scale, 18% of patients had hypopigmented lesions, and 54% had hyperpigmented lesions.
After 16 weeks of treatment, 68% of patients achieved an EASI-75 response, whereas 46% achieved an EASI-90 response, Dr. Waibel reported at the meeting. In addition, 39% of patients achieved an IGA score of 0 or 1, 56% achieved a ≥ 4-point improvement on the Pruritus NRS, and 66% achieved a ≥ 3-point improvement on the Pruritus NRS. The PDCA-Derm score identified improvement in postinflammatory hyperpigmented lesions in 12 of 21 patients and improvement to normal skin tone in six of 21 patients.
“I have a large population [with skin of color in my practice],” Dr. Waibel said. “I usually tell my [patients with postinflammatory hyperpigmentation] that it takes 6 months to see improvement. In this study, we saw patients achieve improvement in skin tone in a 4-month time frame. PIH is sometimes more distressing than a primary condition, whether it’s acne or atopic dermatitis. In this case, it was surprisingly improved with lebrikizumab.”
No new safety signals or serious adverse events were observed. “This is very exciting because it’s the first time there has been a trial focusing on [patients with skin of color] with moderate to severe eczema in skin types IV-VI,” Dr. Waibel said.
In an interview, the study’s lead investigator, Andrew Alexis, MD, MPH, vice chair for diversity and inclusion in the department of dermatology and professor of clinical dermatology at Weill Cornell Medicine, New York City, said that the interim results from this study “ add valuable, clinically relevant data on the treatment of moderate to severe AD in patient populations with skin of color.”
“An interesting finding,” he continued, “was that improvement in postinflammatory hyperpigmented lesions was seen in 12 of 21 patients and improvement to normal skin tone was observed in six of 21 patients at week 16. This is particularly relevant to patients with skin of color who frequently suffer from pigmentary changes in association with their AD.”
Lebrikizumab was approved in November 2023 in Europe for the treatment of moderate to severe AD in people aged 12 years or older and is currently under review by the Food and Drug Administration for treatment of AD.
Both Dr. Waibel and Dr. Alexis disclosed numerous conflicts of interest from various pharmaceutical companies, including serving as a consultant and/or advisor to Eli Lilly and Co.
A version of this article appeared on Medscape.com.
SAN DIEGO — , interim results from a novel phase 3b trial showed.
Lebrikizumab, a novel monoclonal antibody being developed by Eli Lilly and Co, binds with high affinity to interleukin (IL)–13, thereby blocking the downstream effects of IL-13 with high potency, one of the study investigators, Jill S. Waibel, MD, a dermatologist in Miami, said at the annual meeting of the American Academy of Dermatology. Though the efficacy and safety of lebrikizumab to treat moderate to severe AD have been established in phase 3 studies, including subset analyses by race and ethnicity, “there is a paucity of data to guide the treatment of moderate-to-severe AD in populations traditionally under-represented in clinical trials, including patients with skin of color,” she said.
During a late-breaking abstract session, Dr. Waibel presented interim 16-week results from ADmirable, a phase 3b, open-label, 24-week study, was the first study to evaluate the safety and efficacy of lebrikizumab in adult and adolescents with skin of color and moderate to severe AD. At baseline and at 2 weeks, patients received a 500-mg loading dose of lebrikizumab. Through week 16, they received a 250-mg dose every 2 weeks. The study’s primary endpoint was the proportion of patients who achieved a 75% reduction in EASI-75 at week 16. “If they achieved the primary endpoint at week 16, they went to a 250-mg dose every 4 weeks,” Dr. Waibel said. “If they did not achieve that [primary endpoint] they stayed on the 250-mg dose every 2 weeks.”
The analysis included 50 patients with skin types IV, V, and VI who self-reported their race as Black or African American, American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander. They had chronic AD for at least 1 year, moderate to severe disease at baseline, a history of an inadequate response to topical medications, and were naive to biologics indicated for the treatment of AD.
Week 16 outcomes of interest were the EASI, the Investigator’s Global Assessment (IGA) of 0 or 1, the Pruritus Numerical Rating Scale (NRS), and PDCA-Derm, a scale developed by Eli Lilly and Co that was used to compare postinflammatory lesions to unaffected adjacent normal skin. All data for statistical analyses were summarized as observed.
At baseline, the mean age of the 50 patients was 42 years, 46% were women, their mean body mass index was 30.2, and the mean age at AD onset was 23 years. Most study participants (80%) were Black or African American, 14% were Asian, and 6% were American Indian or Alaska Native; 78% were not Hispanic or Latino and 22% were Hispanic or Latino. The mean EASI score was 28.1, the mean body surface area affected was 41.7%, and the mean Pruritus NRS score was 7.2 out of 11. According to the PDCA-Derm scale, 18% of patients had hypopigmented lesions, and 54% had hyperpigmented lesions.
After 16 weeks of treatment, 68% of patients achieved an EASI-75 response, whereas 46% achieved an EASI-90 response, Dr. Waibel reported at the meeting. In addition, 39% of patients achieved an IGA score of 0 or 1, 56% achieved a ≥ 4-point improvement on the Pruritus NRS, and 66% achieved a ≥ 3-point improvement on the Pruritus NRS. The PDCA-Derm score identified improvement in postinflammatory hyperpigmented lesions in 12 of 21 patients and improvement to normal skin tone in six of 21 patients.
“I have a large population [with skin of color in my practice],” Dr. Waibel said. “I usually tell my [patients with postinflammatory hyperpigmentation] that it takes 6 months to see improvement. In this study, we saw patients achieve improvement in skin tone in a 4-month time frame. PIH is sometimes more distressing than a primary condition, whether it’s acne or atopic dermatitis. In this case, it was surprisingly improved with lebrikizumab.”
No new safety signals or serious adverse events were observed. “This is very exciting because it’s the first time there has been a trial focusing on [patients with skin of color] with moderate to severe eczema in skin types IV-VI,” Dr. Waibel said.
In an interview, the study’s lead investigator, Andrew Alexis, MD, MPH, vice chair for diversity and inclusion in the department of dermatology and professor of clinical dermatology at Weill Cornell Medicine, New York City, said that the interim results from this study “ add valuable, clinically relevant data on the treatment of moderate to severe AD in patient populations with skin of color.”
“An interesting finding,” he continued, “was that improvement in postinflammatory hyperpigmented lesions was seen in 12 of 21 patients and improvement to normal skin tone was observed in six of 21 patients at week 16. This is particularly relevant to patients with skin of color who frequently suffer from pigmentary changes in association with their AD.”
Lebrikizumab was approved in November 2023 in Europe for the treatment of moderate to severe AD in people aged 12 years or older and is currently under review by the Food and Drug Administration for treatment of AD.
Both Dr. Waibel and Dr. Alexis disclosed numerous conflicts of interest from various pharmaceutical companies, including serving as a consultant and/or advisor to Eli Lilly and Co.
A version of this article appeared on Medscape.com.
FROM AAD 2024
Topical Roflumilast Effective in 4 Weeks for Atopic Dermatitis in Young Children
SAN DIEGO — Treatment with (AD), according to the results of a phase 3 study reported at the annual meeting of the American Academy of Dermatology.
Among patients treated with roflumilast cream, 0.05%, 25.4% reached the primary endpoint of “clear” or “almost clear” plus a two-grade improvement from baseline at week 4 vs 10.7% among those in the vehicle group (P < .0001) in a phase 3 randomized controlled trial of children. The findings were released in a late-breaker session at the meeting.
Roflumilast cream, 0.3% (Zoryve), is approved by the Food and Drug Administration (FDA) for treating psoriasis in patients 6 years and older, and lower doses are being evaluated for AD: 0.15% for adults and children ages 6 and older, and 0.05% for ages 2-5. Roflumilast is a phosphodiesterase-4 inhibitor. In 2023, the FDA accepted a supplemental drug application from the manufacturer, Arcutis, for roflumilast, 0.15%, for treating AD in patients ages 6 and older, based on the results from two recently published phase 3 trials, INTEGUMENT-1 and INTEGUMENT-2.
The study of younger children, INTEGUMENT-PED, recruited 652 patients aged 2-5 with mild to moderate AD, with a Validated Investigator Global Assessment scale for AD (vlGA-AD) score of 2 or 3, a mean body surface area of 22% overall (range, 3%-82%), and an Eczema Area and Severity Index (EASI) score of at least 5. Of the patients enrolled, 437 were assigned to 0.05% roflumilast cream, applied once a day for 4 weeks (mean age, 3.3 years; 51.6% male; 67.4% White; 15.6% Black; 8.5% Asian; 8.5% other or more than one race; 80.5% not Latino/Hispanic). The remaining 215 children were assigned to vehicle cream and had similar characteristics.
About 52% of the patients in both groups had an inadequate response, intolerance, or contraindications to topical corticosteroids (and about 17% for topical calcineurin inhibitors and about 9% for crisaborole).
The proportions of patients who reached “clear” (0) or “almost clear” (1) on the vlGA-AD scale were 35.4% and 14.6%, respectively, at week 4 (P < .0001) for roflumilast and vehicle, respectively, according to the lead author of the study, Lawrence M. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, who presented the results at the meeting. In addition, 39.4% and 20.6% achieved an EASI-75 (a secondary endpoint), respectively (P < .0001), and itch also improved within 24 hours of starting treatment.
With regard to safety, 29.7% of patients taking roflumilast had treatment-emergent adverse effects (including upper respiratory tract infections in 4.1%) vs 21.9% of those in the vehicle arm (including upper respiratory tract infections in 1.4%). Reports of pain at the administration site were low (1.6% for roflumilast vs 1.9% for vehicle). Only one patient, a 2-year-old girl, had a treatment-emergent serious adverse event. The child, who was in the roflumilast group, had cellulitis involving noneczematous skin and was treated with antibiotics in the hospital for 3 days. The event was not attributed to roflumilast, which was stopped for 5 days, according to Dr. Eichenfield.
In an interview, Fairfield, Connecticut–based dermatologist Brittany Craiglow, MD, who was not involved in the study, said topical roflumilast would be an “important” new treatment because there are still few nonsteroidal options for the treatment of AD in children under 12. “The excellent local tolerability combined with early improvements in itch and skin clearance will make this a particularly attractive option, if approved,” she said.
Dr. Eichenfield disclosed multiple relationships with various drugmakers. He and several other study authors are investigators and/or consultants for Arcutis and received grants/research funding and/or honoraria. Two authors are Arcutis employees. Other disclosure information for the authors was not immediately available. Dr. Craiglow had no disclosures.
A version of this article appeared on Medscape.com .
SAN DIEGO — Treatment with (AD), according to the results of a phase 3 study reported at the annual meeting of the American Academy of Dermatology.
Among patients treated with roflumilast cream, 0.05%, 25.4% reached the primary endpoint of “clear” or “almost clear” plus a two-grade improvement from baseline at week 4 vs 10.7% among those in the vehicle group (P < .0001) in a phase 3 randomized controlled trial of children. The findings were released in a late-breaker session at the meeting.
Roflumilast cream, 0.3% (Zoryve), is approved by the Food and Drug Administration (FDA) for treating psoriasis in patients 6 years and older, and lower doses are being evaluated for AD: 0.15% for adults and children ages 6 and older, and 0.05% for ages 2-5. Roflumilast is a phosphodiesterase-4 inhibitor. In 2023, the FDA accepted a supplemental drug application from the manufacturer, Arcutis, for roflumilast, 0.15%, for treating AD in patients ages 6 and older, based on the results from two recently published phase 3 trials, INTEGUMENT-1 and INTEGUMENT-2.
The study of younger children, INTEGUMENT-PED, recruited 652 patients aged 2-5 with mild to moderate AD, with a Validated Investigator Global Assessment scale for AD (vlGA-AD) score of 2 or 3, a mean body surface area of 22% overall (range, 3%-82%), and an Eczema Area and Severity Index (EASI) score of at least 5. Of the patients enrolled, 437 were assigned to 0.05% roflumilast cream, applied once a day for 4 weeks (mean age, 3.3 years; 51.6% male; 67.4% White; 15.6% Black; 8.5% Asian; 8.5% other or more than one race; 80.5% not Latino/Hispanic). The remaining 215 children were assigned to vehicle cream and had similar characteristics.
About 52% of the patients in both groups had an inadequate response, intolerance, or contraindications to topical corticosteroids (and about 17% for topical calcineurin inhibitors and about 9% for crisaborole).
The proportions of patients who reached “clear” (0) or “almost clear” (1) on the vlGA-AD scale were 35.4% and 14.6%, respectively, at week 4 (P < .0001) for roflumilast and vehicle, respectively, according to the lead author of the study, Lawrence M. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, who presented the results at the meeting. In addition, 39.4% and 20.6% achieved an EASI-75 (a secondary endpoint), respectively (P < .0001), and itch also improved within 24 hours of starting treatment.
With regard to safety, 29.7% of patients taking roflumilast had treatment-emergent adverse effects (including upper respiratory tract infections in 4.1%) vs 21.9% of those in the vehicle arm (including upper respiratory tract infections in 1.4%). Reports of pain at the administration site were low (1.6% for roflumilast vs 1.9% for vehicle). Only one patient, a 2-year-old girl, had a treatment-emergent serious adverse event. The child, who was in the roflumilast group, had cellulitis involving noneczematous skin and was treated with antibiotics in the hospital for 3 days. The event was not attributed to roflumilast, which was stopped for 5 days, according to Dr. Eichenfield.
In an interview, Fairfield, Connecticut–based dermatologist Brittany Craiglow, MD, who was not involved in the study, said topical roflumilast would be an “important” new treatment because there are still few nonsteroidal options for the treatment of AD in children under 12. “The excellent local tolerability combined with early improvements in itch and skin clearance will make this a particularly attractive option, if approved,” she said.
Dr. Eichenfield disclosed multiple relationships with various drugmakers. He and several other study authors are investigators and/or consultants for Arcutis and received grants/research funding and/or honoraria. Two authors are Arcutis employees. Other disclosure information for the authors was not immediately available. Dr. Craiglow had no disclosures.
A version of this article appeared on Medscape.com .
SAN DIEGO — Treatment with (AD), according to the results of a phase 3 study reported at the annual meeting of the American Academy of Dermatology.
Among patients treated with roflumilast cream, 0.05%, 25.4% reached the primary endpoint of “clear” or “almost clear” plus a two-grade improvement from baseline at week 4 vs 10.7% among those in the vehicle group (P < .0001) in a phase 3 randomized controlled trial of children. The findings were released in a late-breaker session at the meeting.
Roflumilast cream, 0.3% (Zoryve), is approved by the Food and Drug Administration (FDA) for treating psoriasis in patients 6 years and older, and lower doses are being evaluated for AD: 0.15% for adults and children ages 6 and older, and 0.05% for ages 2-5. Roflumilast is a phosphodiesterase-4 inhibitor. In 2023, the FDA accepted a supplemental drug application from the manufacturer, Arcutis, for roflumilast, 0.15%, for treating AD in patients ages 6 and older, based on the results from two recently published phase 3 trials, INTEGUMENT-1 and INTEGUMENT-2.
The study of younger children, INTEGUMENT-PED, recruited 652 patients aged 2-5 with mild to moderate AD, with a Validated Investigator Global Assessment scale for AD (vlGA-AD) score of 2 or 3, a mean body surface area of 22% overall (range, 3%-82%), and an Eczema Area and Severity Index (EASI) score of at least 5. Of the patients enrolled, 437 were assigned to 0.05% roflumilast cream, applied once a day for 4 weeks (mean age, 3.3 years; 51.6% male; 67.4% White; 15.6% Black; 8.5% Asian; 8.5% other or more than one race; 80.5% not Latino/Hispanic). The remaining 215 children were assigned to vehicle cream and had similar characteristics.
About 52% of the patients in both groups had an inadequate response, intolerance, or contraindications to topical corticosteroids (and about 17% for topical calcineurin inhibitors and about 9% for crisaborole).
The proportions of patients who reached “clear” (0) or “almost clear” (1) on the vlGA-AD scale were 35.4% and 14.6%, respectively, at week 4 (P < .0001) for roflumilast and vehicle, respectively, according to the lead author of the study, Lawrence M. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, who presented the results at the meeting. In addition, 39.4% and 20.6% achieved an EASI-75 (a secondary endpoint), respectively (P < .0001), and itch also improved within 24 hours of starting treatment.
With regard to safety, 29.7% of patients taking roflumilast had treatment-emergent adverse effects (including upper respiratory tract infections in 4.1%) vs 21.9% of those in the vehicle arm (including upper respiratory tract infections in 1.4%). Reports of pain at the administration site were low (1.6% for roflumilast vs 1.9% for vehicle). Only one patient, a 2-year-old girl, had a treatment-emergent serious adverse event. The child, who was in the roflumilast group, had cellulitis involving noneczematous skin and was treated with antibiotics in the hospital for 3 days. The event was not attributed to roflumilast, which was stopped for 5 days, according to Dr. Eichenfield.
In an interview, Fairfield, Connecticut–based dermatologist Brittany Craiglow, MD, who was not involved in the study, said topical roflumilast would be an “important” new treatment because there are still few nonsteroidal options for the treatment of AD in children under 12. “The excellent local tolerability combined with early improvements in itch and skin clearance will make this a particularly attractive option, if approved,” she said.
Dr. Eichenfield disclosed multiple relationships with various drugmakers. He and several other study authors are investigators and/or consultants for Arcutis and received grants/research funding and/or honoraria. Two authors are Arcutis employees. Other disclosure information for the authors was not immediately available. Dr. Craiglow had no disclosures.
A version of this article appeared on Medscape.com .
FROM AAD 2024
Skin Inflammatory Biomarker Predictive of Atopic Dermatitis in Infants With Filaggrin Wild Genotype
Key clinical point: Increased cytokine S100A8/9 expression on the skin surface in infants with a high risk for atopic dermatitis (AD) at 2 months with filaggrin wild genotype (FLGwt), but not filaggrin loss-of-function mutations (FLGmut), is predictive of AD development and persistence in the first year of life.
Major finding: Increased S100A8/9 titers detected in skin swabs of the antecubital fossa at 8 weeks in infants with FLGwt, but not in those with FLGmut, were associated with AD development in the first year of life (P = .033) and AD persistence of between 6 and 12 months of age (P < .001).
Study details: This single-center study included 86 infants from the STOP AD trial who had at least one parent with a history of AD, asthma, or allergic rhinitis and had either FLGwt or FLGmut.
Disclosures: The cost of the sample analysis was funded by Janssen R&D and Johnson & Johnson Santé Beauté France and the product used in the study was provided by Johnson & Johnson Santé Beauté France. Six authors declared being employees of or having other ties with the Johnson & Johnson family of companies and others. Two authors are coauthors on a patent application in relation to the STOP-AD study. No declaration of conflicting interests was made by CNC.
Source: Stamatas GN, Sato T, Ni Chaoimh C, et al. Early skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants. J Allergy Clin Immunol. 2024 (Mar 7). doi: 10.1016/j.jaci.2024.02.018 Source
Key clinical point: Increased cytokine S100A8/9 expression on the skin surface in infants with a high risk for atopic dermatitis (AD) at 2 months with filaggrin wild genotype (FLGwt), but not filaggrin loss-of-function mutations (FLGmut), is predictive of AD development and persistence in the first year of life.
Major finding: Increased S100A8/9 titers detected in skin swabs of the antecubital fossa at 8 weeks in infants with FLGwt, but not in those with FLGmut, were associated with AD development in the first year of life (P = .033) and AD persistence of between 6 and 12 months of age (P < .001).
Study details: This single-center study included 86 infants from the STOP AD trial who had at least one parent with a history of AD, asthma, or allergic rhinitis and had either FLGwt or FLGmut.
Disclosures: The cost of the sample analysis was funded by Janssen R&D and Johnson & Johnson Santé Beauté France and the product used in the study was provided by Johnson & Johnson Santé Beauté France. Six authors declared being employees of or having other ties with the Johnson & Johnson family of companies and others. Two authors are coauthors on a patent application in relation to the STOP-AD study. No declaration of conflicting interests was made by CNC.
Source: Stamatas GN, Sato T, Ni Chaoimh C, et al. Early skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants. J Allergy Clin Immunol. 2024 (Mar 7). doi: 10.1016/j.jaci.2024.02.018 Source
Key clinical point: Increased cytokine S100A8/9 expression on the skin surface in infants with a high risk for atopic dermatitis (AD) at 2 months with filaggrin wild genotype (FLGwt), but not filaggrin loss-of-function mutations (FLGmut), is predictive of AD development and persistence in the first year of life.
Major finding: Increased S100A8/9 titers detected in skin swabs of the antecubital fossa at 8 weeks in infants with FLGwt, but not in those with FLGmut, were associated with AD development in the first year of life (P = .033) and AD persistence of between 6 and 12 months of age (P < .001).
Study details: This single-center study included 86 infants from the STOP AD trial who had at least one parent with a history of AD, asthma, or allergic rhinitis and had either FLGwt or FLGmut.
Disclosures: The cost of the sample analysis was funded by Janssen R&D and Johnson & Johnson Santé Beauté France and the product used in the study was provided by Johnson & Johnson Santé Beauté France. Six authors declared being employees of or having other ties with the Johnson & Johnson family of companies and others. Two authors are coauthors on a patent application in relation to the STOP-AD study. No declaration of conflicting interests was made by CNC.
Source: Stamatas GN, Sato T, Ni Chaoimh C, et al. Early skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants. J Allergy Clin Immunol. 2024 (Mar 7). doi: 10.1016/j.jaci.2024.02.018 Source
Patients with Atopic Dermatitis Value Safety the Most When Choosing Treatments
Key clinical point: Safety is the most valued treatment attribute for adults with moderate-to-severe atopic dermatitis (AD), followed by the mode of administration, whereas monitoring requirements is the least critical attribute.
Major finding: The risk for severe adverse events emerged as the most important attribute (coefficient 0.42; 95% CI 0.36-0.49), followed by the ease of treatment administration with daily oral pills vs biweekly injections (coefficient 0.41, 95% CI 0.35-0.48). Avoiding monitoring for severe adverse events was the least critical attribute (coefficient 0.02; 95% CI −0.03 to 0.07).
Study details: This study included 713 adults with moderate-to-severe AD having Patient-Oriented Eczema Measure scores > 7 or current or prior exposure to systemic treatment who completed the online discrete choice experiment survey for treatment preferences in AD.
Disclosures: This study was sponsored by LEO Pharma. Five authors declared being employees of LEO Pharma or EY Economics Denmark, a paid vendor of LEO Pharma. Some authors declared serving as advisors, consultants, etc., for or receiving research grants, etc., from LEO Pharma and others.
Source: Ameen M, Alhusayen R, Brandi H, et al. Patient preferences in the treatment of moderate-to-severe atopic dermatitis. Acta Derm Venereol. 2024 (Feb 21). doi: 10.2340/actadv.v104.19454 Source
Key clinical point: Safety is the most valued treatment attribute for adults with moderate-to-severe atopic dermatitis (AD), followed by the mode of administration, whereas monitoring requirements is the least critical attribute.
Major finding: The risk for severe adverse events emerged as the most important attribute (coefficient 0.42; 95% CI 0.36-0.49), followed by the ease of treatment administration with daily oral pills vs biweekly injections (coefficient 0.41, 95% CI 0.35-0.48). Avoiding monitoring for severe adverse events was the least critical attribute (coefficient 0.02; 95% CI −0.03 to 0.07).
Study details: This study included 713 adults with moderate-to-severe AD having Patient-Oriented Eczema Measure scores > 7 or current or prior exposure to systemic treatment who completed the online discrete choice experiment survey for treatment preferences in AD.
Disclosures: This study was sponsored by LEO Pharma. Five authors declared being employees of LEO Pharma or EY Economics Denmark, a paid vendor of LEO Pharma. Some authors declared serving as advisors, consultants, etc., for or receiving research grants, etc., from LEO Pharma and others.
Source: Ameen M, Alhusayen R, Brandi H, et al. Patient preferences in the treatment of moderate-to-severe atopic dermatitis. Acta Derm Venereol. 2024 (Feb 21). doi: 10.2340/actadv.v104.19454 Source
Key clinical point: Safety is the most valued treatment attribute for adults with moderate-to-severe atopic dermatitis (AD), followed by the mode of administration, whereas monitoring requirements is the least critical attribute.
Major finding: The risk for severe adverse events emerged as the most important attribute (coefficient 0.42; 95% CI 0.36-0.49), followed by the ease of treatment administration with daily oral pills vs biweekly injections (coefficient 0.41, 95% CI 0.35-0.48). Avoiding monitoring for severe adverse events was the least critical attribute (coefficient 0.02; 95% CI −0.03 to 0.07).
Study details: This study included 713 adults with moderate-to-severe AD having Patient-Oriented Eczema Measure scores > 7 or current or prior exposure to systemic treatment who completed the online discrete choice experiment survey for treatment preferences in AD.
Disclosures: This study was sponsored by LEO Pharma. Five authors declared being employees of LEO Pharma or EY Economics Denmark, a paid vendor of LEO Pharma. Some authors declared serving as advisors, consultants, etc., for or receiving research grants, etc., from LEO Pharma and others.
Source: Ameen M, Alhusayen R, Brandi H, et al. Patient preferences in the treatment of moderate-to-severe atopic dermatitis. Acta Derm Venereol. 2024 (Feb 21). doi: 10.2340/actadv.v104.19454 Source
Real World Study Confirms Safety and Efficacy of Abrocitinib in Atopic Dermatitis
Key clinical point: Abrocitinib is safe and effective in patients with atopic dermatitis (AD) in daily practice, regardless of their previous inadequate response to upadacitinib or dupilumab.
Major finding: At week 28, 57.6% of patients achieved a ≥75% reduction in the Eczema Area and Severity Index (EASI) scores. At week 16, no significant difference was observed in the EASI scores between nonresponders and patients naive or responsive to upadacitinib or dupilumab (all P > .05). Most adverse events (81.6%) were mild in severity.
Study details: This multicenter prospective study included 103 patients with AD from the BioDay registry who did or did not exhibit adequate response to previous dupilumab or upadacitinib treatment and received abrocitinib for ≤28 weeks.
Disclosures: The BioDay registry was sponsored by Eli Lilly, Sanofi Genzyme, Leo Pharma, AbbVie, and Pfizer. Seven authors reported being consultants, speakers, etc., for or having other ties with various sources, including the aforementioned organizations. The other authors had nothing to disclose.
Source: Kamphuis E, Boesjes CM, Loman L, et al. Real-world experience of abrocitinib treatment in patients with atopic dermatitis and hand eczema: Up to 28-week results from the BioDay Registry. Acta Derm Venereol. 2024 (Feb 7). Doi: 10.2340/actadv.v104.19454 Source
Key clinical point: Abrocitinib is safe and effective in patients with atopic dermatitis (AD) in daily practice, regardless of their previous inadequate response to upadacitinib or dupilumab.
Major finding: At week 28, 57.6% of patients achieved a ≥75% reduction in the Eczema Area and Severity Index (EASI) scores. At week 16, no significant difference was observed in the EASI scores between nonresponders and patients naive or responsive to upadacitinib or dupilumab (all P > .05). Most adverse events (81.6%) were mild in severity.
Study details: This multicenter prospective study included 103 patients with AD from the BioDay registry who did or did not exhibit adequate response to previous dupilumab or upadacitinib treatment and received abrocitinib for ≤28 weeks.
Disclosures: The BioDay registry was sponsored by Eli Lilly, Sanofi Genzyme, Leo Pharma, AbbVie, and Pfizer. Seven authors reported being consultants, speakers, etc., for or having other ties with various sources, including the aforementioned organizations. The other authors had nothing to disclose.
Source: Kamphuis E, Boesjes CM, Loman L, et al. Real-world experience of abrocitinib treatment in patients with atopic dermatitis and hand eczema: Up to 28-week results from the BioDay Registry. Acta Derm Venereol. 2024 (Feb 7). Doi: 10.2340/actadv.v104.19454 Source
Key clinical point: Abrocitinib is safe and effective in patients with atopic dermatitis (AD) in daily practice, regardless of their previous inadequate response to upadacitinib or dupilumab.
Major finding: At week 28, 57.6% of patients achieved a ≥75% reduction in the Eczema Area and Severity Index (EASI) scores. At week 16, no significant difference was observed in the EASI scores between nonresponders and patients naive or responsive to upadacitinib or dupilumab (all P > .05). Most adverse events (81.6%) were mild in severity.
Study details: This multicenter prospective study included 103 patients with AD from the BioDay registry who did or did not exhibit adequate response to previous dupilumab or upadacitinib treatment and received abrocitinib for ≤28 weeks.
Disclosures: The BioDay registry was sponsored by Eli Lilly, Sanofi Genzyme, Leo Pharma, AbbVie, and Pfizer. Seven authors reported being consultants, speakers, etc., for or having other ties with various sources, including the aforementioned organizations. The other authors had nothing to disclose.
Source: Kamphuis E, Boesjes CM, Loman L, et al. Real-world experience of abrocitinib treatment in patients with atopic dermatitis and hand eczema: Up to 28-week results from the BioDay Registry. Acta Derm Venereol. 2024 (Feb 7). Doi: 10.2340/actadv.v104.19454 Source