MDedge Dermatology

Key clinical point: Atopic dermatitis (AD) does not have a significant association with the development of photodermatoses, including photosensitivity, photoallergy, and contact allergy.

Major finding: Of the phototested patients, 23 had a history of AD, of whom 52.2% were photosensitive and 34.8% were photopatch test-positive. Phototested patients with and without AD showed no significant differences in terms of the development of photosensitivity (P = .61), photoallergy (P = .25), or contact allergy (P = .74).

Study details: Findings are from a 10-year retrospective cohort study including 101 patients with or without a history of AD who were tested for sensitivity to UV-A, UV-B, and visible light, followed by photopatch or contact patch testing if photoallergy or simple contact dermatitis was suspected.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Afvari S and Zippin JH. Photodermatoses in patients with atopic dermatitis: A 10-year retrospective cohort study. J Am Acad Dermatol. 2024 (Feb 18). doi: 10.1016/j.jaad.2024.01.032 Source

Key clinical point: Atopic dermatitis (AD) does not have a significant association with the development of photodermatoses, including photosensitivity, photoallergy, and contact allergy.

Major finding: Of the phototested patients, 23 had a history of AD, of whom 52.2% were photosensitive and 34.8% were photopatch test-positive. Phototested patients with and without AD showed no significant differences in terms of the development of photosensitivity (P = .61), photoallergy (P = .25), or contact allergy (P = .74).

Study details: Findings are from a 10-year retrospective cohort study including 101 patients with or without a history of AD who were tested for sensitivity to UV-A, UV-B, and visible light, followed by photopatch or contact patch testing if photoallergy or simple contact dermatitis was suspected.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Afvari S and Zippin JH. Photodermatoses in patients with atopic dermatitis: A 10-year retrospective cohort study. J Am Acad Dermatol. 2024 (Feb 18). doi: 10.1016/j.jaad.2024.01.032 Source

Key clinical point: Atopic dermatitis (AD) does not have a significant association with the development of photodermatoses, including photosensitivity, photoallergy, and contact allergy.

Major finding: Of the phototested patients, 23 had a history of AD, of whom 52.2% were photosensitive and 34.8% were photopatch test-positive. Phototested patients with and without AD showed no significant differences in terms of the development of photosensitivity (P = .61), photoallergy (P = .25), or contact allergy (P = .74).

Study details: Findings are from a 10-year retrospective cohort study including 101 patients with or without a history of AD who were tested for sensitivity to UV-A, UV-B, and visible light, followed by photopatch or contact patch testing if photoallergy or simple contact dermatitis was suspected.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Afvari S and Zippin JH. Photodermatoses in patients with atopic dermatitis: A 10-year retrospective cohort study. J Am Acad Dermatol. 2024 (Feb 18). doi: 10.1016/j.jaad.2024.01.032 Source

Key clinical point: Dupilumab led to rapid and significant improvements in atopic dermatitis (AD) signs and symptoms in children, including those who failed to attain clear or almost clear skin according to Investigator's Global Assessment (IGA).

Major finding: At week 16, the composite endpoint, including ≥50% improvement in Eczema Area and Severity Index scores, was achieved by significantly more children receiving dupilumab vs placebo in the overall group (77.7% vs 24.6%; P < .0001) and the subgroup with an IGA score > 1 (68.9% vs 21.5%; P < .0001). Significant improvements were observed as early as week 2.

Study details: This post hoc analysis of LIBERTY AD PRESCHOOL (Part B) included 162 children age 6 months to 5 years with moderate-to-severe AD who were randomized to receive dupilumab or placebo and low-potency topical corticosteroids, of whom 136 had an IGA score > 1.

Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Three authors reported being employees of or owning stocks or stock options in Sanofi or Regeneron. The remaining authors reported receiving grants from or having other ties with Sanofi, Regeneron, or others.

Source: Cork MJ, Lockshin B, Pinter A, et al. Clinically meaningful responses to dupilumab among children aged 6 months to 5 years with moderate-to-severe atopic dermatitis who did not achieve clear or almost clear skin according to the investigator's global assessment: A post hoc analysis of a phase 3 trial. Acta Derm Venereol. 2024 (Feb 12). doi: 10.2340/actadv.v104.13467 Source

Key clinical point: Dupilumab led to rapid and significant improvements in atopic dermatitis (AD) signs and symptoms in children, including those who failed to attain clear or almost clear skin according to Investigator's Global Assessment (IGA).

Major finding: At week 16, the composite endpoint, including ≥50% improvement in Eczema Area and Severity Index scores, was achieved by significantly more children receiving dupilumab vs placebo in the overall group (77.7% vs 24.6%; P < .0001) and the subgroup with an IGA score > 1 (68.9% vs 21.5%; P < .0001). Significant improvements were observed as early as week 2.

Study details: This post hoc analysis of LIBERTY AD PRESCHOOL (Part B) included 162 children age 6 months to 5 years with moderate-to-severe AD who were randomized to receive dupilumab or placebo and low-potency topical corticosteroids, of whom 136 had an IGA score > 1.

Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Three authors reported being employees of or owning stocks or stock options in Sanofi or Regeneron. The remaining authors reported receiving grants from or having other ties with Sanofi, Regeneron, or others.

Source: Cork MJ, Lockshin B, Pinter A, et al. Clinically meaningful responses to dupilumab among children aged 6 months to 5 years with moderate-to-severe atopic dermatitis who did not achieve clear or almost clear skin according to the investigator's global assessment: A post hoc analysis of a phase 3 trial. Acta Derm Venereol. 2024 (Feb 12). doi: 10.2340/actadv.v104.13467 Source

Key clinical point: Dupilumab led to rapid and significant improvements in atopic dermatitis (AD) signs and symptoms in children, including those who failed to attain clear or almost clear skin according to Investigator's Global Assessment (IGA).

Major finding: At week 16, the composite endpoint, including ≥50% improvement in Eczema Area and Severity Index scores, was achieved by significantly more children receiving dupilumab vs placebo in the overall group (77.7% vs 24.6%; P < .0001) and the subgroup with an IGA score > 1 (68.9% vs 21.5%; P < .0001). Significant improvements were observed as early as week 2.

Study details: This post hoc analysis of LIBERTY AD PRESCHOOL (Part B) included 162 children age 6 months to 5 years with moderate-to-severe AD who were randomized to receive dupilumab or placebo and low-potency topical corticosteroids, of whom 136 had an IGA score > 1.

Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Three authors reported being employees of or owning stocks or stock options in Sanofi or Regeneron. The remaining authors reported receiving grants from or having other ties with Sanofi, Regeneron, or others.

Source: Cork MJ, Lockshin B, Pinter A, et al. Clinically meaningful responses to dupilumab among children aged 6 months to 5 years with moderate-to-severe atopic dermatitis who did not achieve clear or almost clear skin according to the investigator's global assessment: A post hoc analysis of a phase 3 trial. Acta Derm Venereol. 2024 (Feb 12). doi: 10.2340/actadv.v104.13467 Source

Key clinical point: Both the age of onset and persistence of atopic dermatitis (AD) are differentially associated with the expression and progression of other atopic diseases during childhood.

Major finding: Children who developed AD at 1 year of age (persistent AD) showed significantly higher rates of food allergy (P = .004), asthma (P < .001), and self-reported rhinitis (P < .001) during childhood compared with children without AD at age 1 year (none/intermittent AD [never had AD or had an intermittent course] or late-onset AD [onset from 4-6 years of age]).

Study details: This study included 285 children from the Childhood Origins of ASThma cohort with a history of physician-diagnosed asthma or respiratory allergies who were followed up to 18 years of age and categorized based on AD phenotypes into none/intermittent (n = 180), late-onset (n = 38), or persistent (n = 67) AD groups.

Disclosures: This study was funded by the US National Institutes of Health (NIH) and the US National Heart, Lung, and Blood Institute. Two authors declared receiving funding from or having other ties with various sources, including NIH.

Source: Taki MH, Lee KE, Gangnon R, et al. Atopic dermatitis phenotypes impact expression of atopic diseases despite similar mononuclear cell cytokine responses. J Allergy Clin Immunol. 2024 (Mar 2). doi: 10.1016/j.jaci.2024.02.015 Source

Key clinical point: Both the age of onset and persistence of atopic dermatitis (AD) are differentially associated with the expression and progression of other atopic diseases during childhood.

Major finding: Children who developed AD at 1 year of age (persistent AD) showed significantly higher rates of food allergy (P = .004), asthma (P < .001), and self-reported rhinitis (P < .001) during childhood compared with children without AD at age 1 year (none/intermittent AD [never had AD or had an intermittent course] or late-onset AD [onset from 4-6 years of age]).

Study details: This study included 285 children from the Childhood Origins of ASThma cohort with a history of physician-diagnosed asthma or respiratory allergies who were followed up to 18 years of age and categorized based on AD phenotypes into none/intermittent (n = 180), late-onset (n = 38), or persistent (n = 67) AD groups.

Disclosures: This study was funded by the US National Institutes of Health (NIH) and the US National Heart, Lung, and Blood Institute. Two authors declared receiving funding from or having other ties with various sources, including NIH.

Source: Taki MH, Lee KE, Gangnon R, et al. Atopic dermatitis phenotypes impact expression of atopic diseases despite similar mononuclear cell cytokine responses. J Allergy Clin Immunol. 2024 (Mar 2). doi: 10.1016/j.jaci.2024.02.015 Source

Key clinical point: Both the age of onset and persistence of atopic dermatitis (AD) are differentially associated with the expression and progression of other atopic diseases during childhood.

Major finding: Children who developed AD at 1 year of age (persistent AD) showed significantly higher rates of food allergy (P = .004), asthma (P < .001), and self-reported rhinitis (P < .001) during childhood compared with children without AD at age 1 year (none/intermittent AD [never had AD or had an intermittent course] or late-onset AD [onset from 4-6 years of age]).

Study details: This study included 285 children from the Childhood Origins of ASThma cohort with a history of physician-diagnosed asthma or respiratory allergies who were followed up to 18 years of age and categorized based on AD phenotypes into none/intermittent (n = 180), late-onset (n = 38), or persistent (n = 67) AD groups.

Disclosures: This study was funded by the US National Institutes of Health (NIH) and the US National Heart, Lung, and Blood Institute. Two authors declared receiving funding from or having other ties with various sources, including NIH.

Source: Taki MH, Lee KE, Gangnon R, et al. Atopic dermatitis phenotypes impact expression of atopic diseases despite similar mononuclear cell cytokine responses. J Allergy Clin Immunol. 2024 (Mar 2). doi: 10.1016/j.jaci.2024.02.015 Source

Key clinical point: Children who later developed atopic dermatitis (AD) had a delayed maturation of the skin microbiome and increased levels of proinflammatory stratum corneum biomarkers before AD onset.

Major finding: Children who did vs did not develop AD later had significantly increased levels of stratum corneum biomarkers (thymus and activation-regulated chemokine, interleukin-18, monocyte chemoattractant protein-1, interleukin-22, etc.; all P ≤ .01) and greater variance over time in the most abundant 14 core amplicon sequence variants (P = .04), indicating delayed establishment of a stable skin microbiome.

Study details: This study longitudinally analyzed the epidermal biomarker levels and microbiome profiles of 50 children who were at a high risk for AD from a previous randomized study, of whom 26% of children developed AD up to month 24.

Disclosures: This study was supported by the BIOMAP project, LA ROCHE-POSAY Laboratoire Pharmaceutique, France, and others. Four authors declared receiving institutional research grants, honoraria for consulting, etc., from or having other ties with various sources.

Source: Fonfara M, Hartmann J, Stölzl D, et al. Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis. J Eur Acad Dermatol Venereol. 2024 (Feb 29). doi: 10.1111/jdv.19932 Source

Key clinical point: Children who later developed atopic dermatitis (AD) had a delayed maturation of the skin microbiome and increased levels of proinflammatory stratum corneum biomarkers before AD onset.

Major finding: Children who did vs did not develop AD later had significantly increased levels of stratum corneum biomarkers (thymus and activation-regulated chemokine, interleukin-18, monocyte chemoattractant protein-1, interleukin-22, etc.; all P ≤ .01) and greater variance over time in the most abundant 14 core amplicon sequence variants (P = .04), indicating delayed establishment of a stable skin microbiome.

Study details: This study longitudinally analyzed the epidermal biomarker levels and microbiome profiles of 50 children who were at a high risk for AD from a previous randomized study, of whom 26% of children developed AD up to month 24.

Disclosures: This study was supported by the BIOMAP project, LA ROCHE-POSAY Laboratoire Pharmaceutique, France, and others. Four authors declared receiving institutional research grants, honoraria for consulting, etc., from or having other ties with various sources.

Source: Fonfara M, Hartmann J, Stölzl D, et al. Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis. J Eur Acad Dermatol Venereol. 2024 (Feb 29). doi: 10.1111/jdv.19932 Source

Key clinical point: Children who later developed atopic dermatitis (AD) had a delayed maturation of the skin microbiome and increased levels of proinflammatory stratum corneum biomarkers before AD onset.

Major finding: Children who did vs did not develop AD later had significantly increased levels of stratum corneum biomarkers (thymus and activation-regulated chemokine, interleukin-18, monocyte chemoattractant protein-1, interleukin-22, etc.; all P ≤ .01) and greater variance over time in the most abundant 14 core amplicon sequence variants (P = .04), indicating delayed establishment of a stable skin microbiome.

Study details: This study longitudinally analyzed the epidermal biomarker levels and microbiome profiles of 50 children who were at a high risk for AD from a previous randomized study, of whom 26% of children developed AD up to month 24.

Disclosures: This study was supported by the BIOMAP project, LA ROCHE-POSAY Laboratoire Pharmaceutique, France, and others. Four authors declared receiving institutional research grants, honoraria for consulting, etc., from or having other ties with various sources.

Source: Fonfara M, Hartmann J, Stölzl D, et al. Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis. J Eur Acad Dermatol Venereol. 2024 (Feb 29). doi: 10.1111/jdv.19932 Source

Key clinical point: The presence of atopic dermatitis (AD) symptoms in children during early life is associated with increased likelihood of pain at 10 years of age, suggesting a prospective influence of AD on pain experiences in children.

Major finding: Children with AD-like symptoms at 6 and 15 months of age had a significantly higher risk of reporting any pain (relative risk [RR] 1.75; 95% CI 1.15-2.66) and multisite pain (RR 1.67; 95% CI 1.18-2.37), respectively, at age 10 years.

Study details: This prospective study analyzed the data of 1302 and 874 children from the Generation XXI birth cohort for AD-like symptoms at ages 6 months and 15 months, respectively, by interviewing parents; data on pain history in the last 3 months at age 10 years was collected using structured questionnaires for parents and children.

Disclosures: This study was funded by the European Regional Development Fund, through COMPETE 2020 Operational Programme 'Competitiveness and Internationalization,' projects at the Univeridade do Porto, Portugal, and others. The authors declared no conflicts of interest.

Source: Gorito V, Brandão M, Azevedo I, et al. Atopic dermatitis in early life and pain at 10 years of age: An exploratory study. Eur J Pediatr. 2024 (Feb 24). doi: 10.1007/s00431-024-05439-0 Source

Key clinical point: The presence of atopic dermatitis (AD) symptoms in children during early life is associated with increased likelihood of pain at 10 years of age, suggesting a prospective influence of AD on pain experiences in children.

Major finding: Children with AD-like symptoms at 6 and 15 months of age had a significantly higher risk of reporting any pain (relative risk [RR] 1.75; 95% CI 1.15-2.66) and multisite pain (RR 1.67; 95% CI 1.18-2.37), respectively, at age 10 years.

Study details: This prospective study analyzed the data of 1302 and 874 children from the Generation XXI birth cohort for AD-like symptoms at ages 6 months and 15 months, respectively, by interviewing parents; data on pain history in the last 3 months at age 10 years was collected using structured questionnaires for parents and children.

Disclosures: This study was funded by the European Regional Development Fund, through COMPETE 2020 Operational Programme 'Competitiveness and Internationalization,' projects at the Univeridade do Porto, Portugal, and others. The authors declared no conflicts of interest.

Source: Gorito V, Brandão M, Azevedo I, et al. Atopic dermatitis in early life and pain at 10 years of age: An exploratory study. Eur J Pediatr. 2024 (Feb 24). doi: 10.1007/s00431-024-05439-0 Source

Key clinical point: The presence of atopic dermatitis (AD) symptoms in children during early life is associated with increased likelihood of pain at 10 years of age, suggesting a prospective influence of AD on pain experiences in children.

Major finding: Children with AD-like symptoms at 6 and 15 months of age had a significantly higher risk of reporting any pain (relative risk [RR] 1.75; 95% CI 1.15-2.66) and multisite pain (RR 1.67; 95% CI 1.18-2.37), respectively, at age 10 years.

Study details: This prospective study analyzed the data of 1302 and 874 children from the Generation XXI birth cohort for AD-like symptoms at ages 6 months and 15 months, respectively, by interviewing parents; data on pain history in the last 3 months at age 10 years was collected using structured questionnaires for parents and children.

Disclosures: This study was funded by the European Regional Development Fund, through COMPETE 2020 Operational Programme 'Competitiveness and Internationalization,' projects at the Univeridade do Porto, Portugal, and others. The authors declared no conflicts of interest.

Source: Gorito V, Brandão M, Azevedo I, et al. Atopic dermatitis in early life and pain at 10 years of age: An exploratory study. Eur J Pediatr. 2024 (Feb 24). doi: 10.1007/s00431-024-05439-0 Source

Key clinical point: Topical Streptococcus postbiotic emollient (strain CX) demonstrated superior efficacy in improving disease activity outcomes and a tolerable safety profile in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: At week 8, a higher percentage of patients in the topical Streptococcus postbiotic emollient vs placebo group (41.5% vs 12.1%; P = .005) achieved an Investigator’s Global Assessment score of 0 or 1 and a reduction of ≥1 point from baseline. No significant safety issues were identified during the study.

Study details: Findings are from a proof-of-concept trial including 98 patients with mild-to-moderate AD (age 12-70 years) who were randomly assigned 2:1 to receive daily topical 1.0% Strain CX postbiotic emollient (n = 65) or placebo (n = 33) for 8 weeks.

Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korea government and Cosmax BTI. The authors declared no conflicts of interest.

Source: Kim MS, Kim HJ, Kang SM, Heo YM, Kang J, et al. Efficacy and safety of topical Streptococcus postbiotic emollient in adolescents and adults with mild-to-moderate atopic dermatitis: A randomized, double-blind, vehicle-controlled trial. Allergy. 2024 (Mar 4). doi: 10.1111/all.16077 Source

Key clinical point: Topical Streptococcus postbiotic emollient (strain CX) demonstrated superior efficacy in improving disease activity outcomes and a tolerable safety profile in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: At week 8, a higher percentage of patients in the topical Streptococcus postbiotic emollient vs placebo group (41.5% vs 12.1%; P = .005) achieved an Investigator’s Global Assessment score of 0 or 1 and a reduction of ≥1 point from baseline. No significant safety issues were identified during the study.

Study details: Findings are from a proof-of-concept trial including 98 patients with mild-to-moderate AD (age 12-70 years) who were randomly assigned 2:1 to receive daily topical 1.0% Strain CX postbiotic emollient (n = 65) or placebo (n = 33) for 8 weeks.

Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korea government and Cosmax BTI. The authors declared no conflicts of interest.

Source: Kim MS, Kim HJ, Kang SM, Heo YM, Kang J, et al. Efficacy and safety of topical Streptococcus postbiotic emollient in adolescents and adults with mild-to-moderate atopic dermatitis: A randomized, double-blind, vehicle-controlled trial. Allergy. 2024 (Mar 4). doi: 10.1111/all.16077 Source

Key clinical point: Topical Streptococcus postbiotic emollient (strain CX) demonstrated superior efficacy in improving disease activity outcomes and a tolerable safety profile in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: At week 8, a higher percentage of patients in the topical Streptococcus postbiotic emollient vs placebo group (41.5% vs 12.1%; P = .005) achieved an Investigator’s Global Assessment score of 0 or 1 and a reduction of ≥1 point from baseline. No significant safety issues were identified during the study.

Study details: Findings are from a proof-of-concept trial including 98 patients with mild-to-moderate AD (age 12-70 years) who were randomly assigned 2:1 to receive daily topical 1.0% Strain CX postbiotic emollient (n = 65) or placebo (n = 33) for 8 weeks.

Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korea government and Cosmax BTI. The authors declared no conflicts of interest.

Source: Kim MS, Kim HJ, Kang SM, Heo YM, Kang J, et al. Efficacy and safety of topical Streptococcus postbiotic emollient in adolescents and adults with mild-to-moderate atopic dermatitis: A randomized, double-blind, vehicle-controlled trial. Allergy. 2024 (Mar 4). doi: 10.1111/all.16077 Source

Key clinical point: Atopic dermatitis (AD) is associated with a higher likelihood of cognitive impairment symptoms involving difficulties in learning or memory, especially in children with neurodevelopmental comorbidities, such as attention-deficit/hyperactivity disorder (ADHD) or learning disability.

Major finding: A significantly greater number of children with vs without AD experienced difficulties with learning (10.8% vs 5.9%) and memory (11.1% vs 5.8%; both P < .001). However, this association was observed only in children with neurodevelopmental disorders (adjusted odds ratio 2.26; 95% CI 1.43-3.57) including ADHD or learning disabilities.

Study details: This cross-sectional study analyzed the data of 7957 children, representing a weighted total of 69,732,807 children without intellectual disabilities from the 2021 US National Health Interview Survey who did (n = 9,223,013) or did not (n = 60,509,794) have AD. The survey randomly selects 1 child per surveyed household for whom a parent or adult caregiver provides information.

Disclosures: This study was supported by a grant to Joy Wan from the US National Institutes of Health. Joy Wan also declared receiving a grant and personal fees from various pharmaceutical companies. The other authors declared no conflicts of interest.

Source: Ma EZ, Chang HR, Radtke S, Wan J. Symptoms of cognitive impairment among children with atopic dermatitis. JAMA Dermatol. 2024 (Mar 6). doi: 10.1001/jamadermatol.2024.0015 Source

Key clinical point: Atopic dermatitis (AD) is associated with a higher likelihood of cognitive impairment symptoms involving difficulties in learning or memory, especially in children with neurodevelopmental comorbidities, such as attention-deficit/hyperactivity disorder (ADHD) or learning disability.

Major finding: A significantly greater number of children with vs without AD experienced difficulties with learning (10.8% vs 5.9%) and memory (11.1% vs 5.8%; both P < .001). However, this association was observed only in children with neurodevelopmental disorders (adjusted odds ratio 2.26; 95% CI 1.43-3.57) including ADHD or learning disabilities.

Study details: This cross-sectional study analyzed the data of 7957 children, representing a weighted total of 69,732,807 children without intellectual disabilities from the 2021 US National Health Interview Survey who did (n = 9,223,013) or did not (n = 60,509,794) have AD. The survey randomly selects 1 child per surveyed household for whom a parent or adult caregiver provides information.

Disclosures: This study was supported by a grant to Joy Wan from the US National Institutes of Health. Joy Wan also declared receiving a grant and personal fees from various pharmaceutical companies. The other authors declared no conflicts of interest.

Source: Ma EZ, Chang HR, Radtke S, Wan J. Symptoms of cognitive impairment among children with atopic dermatitis. JAMA Dermatol. 2024 (Mar 6). doi: 10.1001/jamadermatol.2024.0015 Source

Key clinical point: Atopic dermatitis (AD) is associated with a higher likelihood of cognitive impairment symptoms involving difficulties in learning or memory, especially in children with neurodevelopmental comorbidities, such as attention-deficit/hyperactivity disorder (ADHD) or learning disability.

Major finding: A significantly greater number of children with vs without AD experienced difficulties with learning (10.8% vs 5.9%) and memory (11.1% vs 5.8%; both P < .001). However, this association was observed only in children with neurodevelopmental disorders (adjusted odds ratio 2.26; 95% CI 1.43-3.57) including ADHD or learning disabilities.

Study details: This cross-sectional study analyzed the data of 7957 children, representing a weighted total of 69,732,807 children without intellectual disabilities from the 2021 US National Health Interview Survey who did (n = 9,223,013) or did not (n = 60,509,794) have AD. The survey randomly selects 1 child per surveyed household for whom a parent or adult caregiver provides information.

Disclosures: This study was supported by a grant to Joy Wan from the US National Institutes of Health. Joy Wan also declared receiving a grant and personal fees from various pharmaceutical companies. The other authors declared no conflicts of interest.

Source: Ma EZ, Chang HR, Radtke S, Wan J. Symptoms of cognitive impairment among children with atopic dermatitis. JAMA Dermatol. 2024 (Mar 6). doi: 10.1001/jamadermatol.2024.0015 Source

Sublingual immunotherapy (SLIT) is as safe and effective for high-risk older children and adolescents as oral immunotherapy (OIT) is for infants and preschoolers, according to new research.

Preliminary data from a study of more than 180 pediatric patients with multiple food allergies showed that while most patients had mild symptoms, none experienced a severe grade 4 reaction during the buildup and maintenance phase of SLIT.

In addition, 70% of those tested at the end of the treatment protocol were able to tolerate 300 mg of their allergen, a success rate nearly as high as that for OIT.

The study was published in The Journal of Allergy and Clinical Immunology: In Practice.

SLIT has been used successfully in the treatment of environmental allergens such as grass and tree pollen and dust mites. In this study, researchers decided to test SLIT’s effectiveness and safety in the treatment of food allergies in older children.

“We knew that OIT is very effective and safe in infants and toddlers, but there was literature illustrating that for older, school-age kids and adolescents, OIT is not safe enough, as those older age groups tend to have higher risk of severe reaction during treatment,” senior author Edmond Chan, MD, clinical professor of allergy at the University of British Columbia and pediatric allergist at BC Children’s Hospital, both in Vancouver, British Columbia, Canada, told this news organization. “With that knowledge, we decided to explore SLIT as another first-phase therapy for the older kids.”

The investigators recruited 188 high-risk older children aged 4-18 years for multifood SLIT. Most (61.7%) participants had multiple food allergies. Approximately 68% were male, and the population’s median age was 11.3 years.

Nearly half (48.4%) of participants had atopic dermatitis, 45.2% had asthma, 58.0% had allergic rhinitis, and 2.66% had preexisting eosinophilic esophagitis.

Most (75.0%) of the children were classified as higher risk, and 23 had a history of a grade 3 or 4 reaction before beginning SLIT.

Of the 188 children who were initially enrolled in the study, 173 (92.0%) finished their SLIT buildup phase.

Because the study started when COVID-19 pandemic restrictions were in place, the SLIT protocol mandated that patients be seen virtually. The patients’ caregivers learned how to mix and administer the required doses at home using recipes specially developed by the research team that used products bought at the grocery store.

A wide variety of food allergens were treated, including peanut, other legumes, tree nuts, sesame, other seeds, egg, cow’s milk, fish, wheat, shrimp, and other allergens.

The children built up to 2-mg protein SLIT maintenance over the course of three to five visits under nurse supervision.

After 1-2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC; cumulative dose: 300 mg of protein) with the goal of bypassing OIT buildup.

Nearly all patients (93.1%) had symptoms during SLIT buildup, but most were mild grade 1 (52.1%) or 2 (40.4%) reactions. Only one patient had a grade 3 reaction. None of the patients experienced a severe grade 4 reaction.

The most common grade 1 reaction was oral itch, an expected symptom of SLIT, which occurred in 82.7% of the patients.

Four patients (2.10%) received epinephrine during buildup and went to the emergency department. All these patients returned to continue SLIT without further need for epinephrine.

To test the effectiveness of SLIT, the researchers performed 50 low-dose OFCs in 20 patients. Of these food challenges, 35 (70%) were successful, and patients were asked to start daily 300-mg OIT maintenance, thus bypassing OIT buildup.

An additional nine OFCs that were unsuccessful were counseled to self-escalate from 80 mg or higher to 300 mg at home with medical guidance as needed.

“Our preliminary data of 20 patients and 50 low-dose oral food challenges suggest that an initial phase of 1-2 years of 2-mg daily SLIT therapy may be a safe and effective way to bypass the OIT buildup phase without the need for dozens of in-person visits with an allergist,” said Dr. Chan.

“So now we have the best of both worlds. We harness the safety of SLIT for the first 1-2 years, with the effectiveness of OIT for the remainder of the treatment period,” he said.
 

Adds to Evidence

Commenting on the study for this news organization, Julia Upton, MD, associate professor of pediatrics at the University of Toronto, Toronto, Ontario, Canada, said, “This study adds to the evidence that consistent, low exposure to food drives meaningful desensitization far above the daily dose.” Upton did not participate in the research.

“Prior prospective studies in SLIT demonstrated that small single-digit-milligram doses and time greatly increased the threshold of reaction. This real-world report suggests that a way to utilize that threshold increase is by switching to a commonly used maintenance dose of OIT,” said Dr. Upton.

“Although few patients have been assessed for the 300-mg challenge, this study is notable for the age group of 4-18 years, and that many of the patients had reacted to low doses in the past. It also shows that many families are capable of diluting and mixing their own immunotherapy solutions with store-bought foods under the guidance of an experienced allergy clinic,” she added.

“Overall, evidence is building that by various routes, initial small amounts with minimal updoses, plus the tincture of time, may be preferred to multiple frequent updosing from multiple perspectives, including safety, feasibility, cost, and medical resources. It will also be important to understand the preferences and goals of the patient and family as various regimens become more available,” Dr. Upton concluded.

The study was funded by BC Children’s Hospital Foundation. Dr. Chan reported receiving research support from DVB Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi, Genzyme, Bausch Health, Avir Pharma, AstraZeneca, ALK, and Alladapt; and was a colead of the CSACI OIT guidelines. Dr. Upton reported research support/grants from Novartis, Regeneron, Sanofi, ALK Abello, DBV Technologies, CIHR, and SickKids Food Allergy and Anaphylaxis Program and fees from Pfizer, ALK Abello, Bausch Health, Astra Zeneca, and Pharming. She serves as an associate editor for Allergy, Asthma & Clinical Immunology and is on the Board of Directors of Canadian Society of Allergy and Clinical Immunology and the Healthcare Advisory Board of Food Allergy Canada.

A version of this article appeared on Medscape.com .

Sublingual immunotherapy (SLIT) is as safe and effective for high-risk older children and adolescents as oral immunotherapy (OIT) is for infants and preschoolers, according to new research.

Preliminary data from a study of more than 180 pediatric patients with multiple food allergies showed that while most patients had mild symptoms, none experienced a severe grade 4 reaction during the buildup and maintenance phase of SLIT.

In addition, 70% of those tested at the end of the treatment protocol were able to tolerate 300 mg of their allergen, a success rate nearly as high as that for OIT.

The study was published in The Journal of Allergy and Clinical Immunology: In Practice.

SLIT has been used successfully in the treatment of environmental allergens such as grass and tree pollen and dust mites. In this study, researchers decided to test SLIT’s effectiveness and safety in the treatment of food allergies in older children.

“We knew that OIT is very effective and safe in infants and toddlers, but there was literature illustrating that for older, school-age kids and adolescents, OIT is not safe enough, as those older age groups tend to have higher risk of severe reaction during treatment,” senior author Edmond Chan, MD, clinical professor of allergy at the University of British Columbia and pediatric allergist at BC Children’s Hospital, both in Vancouver, British Columbia, Canada, told this news organization. “With that knowledge, we decided to explore SLIT as another first-phase therapy for the older kids.”

The investigators recruited 188 high-risk older children aged 4-18 years for multifood SLIT. Most (61.7%) participants had multiple food allergies. Approximately 68% were male, and the population’s median age was 11.3 years.

Nearly half (48.4%) of participants had atopic dermatitis, 45.2% had asthma, 58.0% had allergic rhinitis, and 2.66% had preexisting eosinophilic esophagitis.

Most (75.0%) of the children were classified as higher risk, and 23 had a history of a grade 3 or 4 reaction before beginning SLIT.

Of the 188 children who were initially enrolled in the study, 173 (92.0%) finished their SLIT buildup phase.

Because the study started when COVID-19 pandemic restrictions were in place, the SLIT protocol mandated that patients be seen virtually. The patients’ caregivers learned how to mix and administer the required doses at home using recipes specially developed by the research team that used products bought at the grocery store.

A wide variety of food allergens were treated, including peanut, other legumes, tree nuts, sesame, other seeds, egg, cow’s milk, fish, wheat, shrimp, and other allergens.

The children built up to 2-mg protein SLIT maintenance over the course of three to five visits under nurse supervision.

After 1-2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC; cumulative dose: 300 mg of protein) with the goal of bypassing OIT buildup.

Nearly all patients (93.1%) had symptoms during SLIT buildup, but most were mild grade 1 (52.1%) or 2 (40.4%) reactions. Only one patient had a grade 3 reaction. None of the patients experienced a severe grade 4 reaction.

The most common grade 1 reaction was oral itch, an expected symptom of SLIT, which occurred in 82.7% of the patients.

Four patients (2.10%) received epinephrine during buildup and went to the emergency department. All these patients returned to continue SLIT without further need for epinephrine.

To test the effectiveness of SLIT, the researchers performed 50 low-dose OFCs in 20 patients. Of these food challenges, 35 (70%) were successful, and patients were asked to start daily 300-mg OIT maintenance, thus bypassing OIT buildup.

An additional nine OFCs that were unsuccessful were counseled to self-escalate from 80 mg or higher to 300 mg at home with medical guidance as needed.

“Our preliminary data of 20 patients and 50 low-dose oral food challenges suggest that an initial phase of 1-2 years of 2-mg daily SLIT therapy may be a safe and effective way to bypass the OIT buildup phase without the need for dozens of in-person visits with an allergist,” said Dr. Chan.

“So now we have the best of both worlds. We harness the safety of SLIT for the first 1-2 years, with the effectiveness of OIT for the remainder of the treatment period,” he said.
 

Adds to Evidence

Commenting on the study for this news organization, Julia Upton, MD, associate professor of pediatrics at the University of Toronto, Toronto, Ontario, Canada, said, “This study adds to the evidence that consistent, low exposure to food drives meaningful desensitization far above the daily dose.” Upton did not participate in the research.

“Prior prospective studies in SLIT demonstrated that small single-digit-milligram doses and time greatly increased the threshold of reaction. This real-world report suggests that a way to utilize that threshold increase is by switching to a commonly used maintenance dose of OIT,” said Dr. Upton.

“Although few patients have been assessed for the 300-mg challenge, this study is notable for the age group of 4-18 years, and that many of the patients had reacted to low doses in the past. It also shows that many families are capable of diluting and mixing their own immunotherapy solutions with store-bought foods under the guidance of an experienced allergy clinic,” she added.

“Overall, evidence is building that by various routes, initial small amounts with minimal updoses, plus the tincture of time, may be preferred to multiple frequent updosing from multiple perspectives, including safety, feasibility, cost, and medical resources. It will also be important to understand the preferences and goals of the patient and family as various regimens become more available,” Dr. Upton concluded.

The study was funded by BC Children’s Hospital Foundation. Dr. Chan reported receiving research support from DVB Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi, Genzyme, Bausch Health, Avir Pharma, AstraZeneca, ALK, and Alladapt; and was a colead of the CSACI OIT guidelines. Dr. Upton reported research support/grants from Novartis, Regeneron, Sanofi, ALK Abello, DBV Technologies, CIHR, and SickKids Food Allergy and Anaphylaxis Program and fees from Pfizer, ALK Abello, Bausch Health, Astra Zeneca, and Pharming. She serves as an associate editor for Allergy, Asthma & Clinical Immunology and is on the Board of Directors of Canadian Society of Allergy and Clinical Immunology and the Healthcare Advisory Board of Food Allergy Canada.

A version of this article appeared on Medscape.com .

Sublingual immunotherapy (SLIT) is as safe and effective for high-risk older children and adolescents as oral immunotherapy (OIT) is for infants and preschoolers, according to new research.

Preliminary data from a study of more than 180 pediatric patients with multiple food allergies showed that while most patients had mild symptoms, none experienced a severe grade 4 reaction during the buildup and maintenance phase of SLIT.

In addition, 70% of those tested at the end of the treatment protocol were able to tolerate 300 mg of their allergen, a success rate nearly as high as that for OIT.

The study was published in The Journal of Allergy and Clinical Immunology: In Practice.

SLIT has been used successfully in the treatment of environmental allergens such as grass and tree pollen and dust mites. In this study, researchers decided to test SLIT’s effectiveness and safety in the treatment of food allergies in older children.

“We knew that OIT is very effective and safe in infants and toddlers, but there was literature illustrating that for older, school-age kids and adolescents, OIT is not safe enough, as those older age groups tend to have higher risk of severe reaction during treatment,” senior author Edmond Chan, MD, clinical professor of allergy at the University of British Columbia and pediatric allergist at BC Children’s Hospital, both in Vancouver, British Columbia, Canada, told this news organization. “With that knowledge, we decided to explore SLIT as another first-phase therapy for the older kids.”

The investigators recruited 188 high-risk older children aged 4-18 years for multifood SLIT. Most (61.7%) participants had multiple food allergies. Approximately 68% were male, and the population’s median age was 11.3 years.

Nearly half (48.4%) of participants had atopic dermatitis, 45.2% had asthma, 58.0% had allergic rhinitis, and 2.66% had preexisting eosinophilic esophagitis.

Most (75.0%) of the children were classified as higher risk, and 23 had a history of a grade 3 or 4 reaction before beginning SLIT.

Of the 188 children who were initially enrolled in the study, 173 (92.0%) finished their SLIT buildup phase.

Because the study started when COVID-19 pandemic restrictions were in place, the SLIT protocol mandated that patients be seen virtually. The patients’ caregivers learned how to mix and administer the required doses at home using recipes specially developed by the research team that used products bought at the grocery store.

A wide variety of food allergens were treated, including peanut, other legumes, tree nuts, sesame, other seeds, egg, cow’s milk, fish, wheat, shrimp, and other allergens.

The children built up to 2-mg protein SLIT maintenance over the course of three to five visits under nurse supervision.

After 1-2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC; cumulative dose: 300 mg of protein) with the goal of bypassing OIT buildup.

Nearly all patients (93.1%) had symptoms during SLIT buildup, but most were mild grade 1 (52.1%) or 2 (40.4%) reactions. Only one patient had a grade 3 reaction. None of the patients experienced a severe grade 4 reaction.

The most common grade 1 reaction was oral itch, an expected symptom of SLIT, which occurred in 82.7% of the patients.

Four patients (2.10%) received epinephrine during buildup and went to the emergency department. All these patients returned to continue SLIT without further need for epinephrine.

To test the effectiveness of SLIT, the researchers performed 50 low-dose OFCs in 20 patients. Of these food challenges, 35 (70%) were successful, and patients were asked to start daily 300-mg OIT maintenance, thus bypassing OIT buildup.

An additional nine OFCs that were unsuccessful were counseled to self-escalate from 80 mg or higher to 300 mg at home with medical guidance as needed.

“Our preliminary data of 20 patients and 50 low-dose oral food challenges suggest that an initial phase of 1-2 years of 2-mg daily SLIT therapy may be a safe and effective way to bypass the OIT buildup phase without the need for dozens of in-person visits with an allergist,” said Dr. Chan.

“So now we have the best of both worlds. We harness the safety of SLIT for the first 1-2 years, with the effectiveness of OIT for the remainder of the treatment period,” he said.
 

Adds to Evidence

Commenting on the study for this news organization, Julia Upton, MD, associate professor of pediatrics at the University of Toronto, Toronto, Ontario, Canada, said, “This study adds to the evidence that consistent, low exposure to food drives meaningful desensitization far above the daily dose.” Upton did not participate in the research.

“Prior prospective studies in SLIT demonstrated that small single-digit-milligram doses and time greatly increased the threshold of reaction. This real-world report suggests that a way to utilize that threshold increase is by switching to a commonly used maintenance dose of OIT,” said Dr. Upton.

“Although few patients have been assessed for the 300-mg challenge, this study is notable for the age group of 4-18 years, and that many of the patients had reacted to low doses in the past. It also shows that many families are capable of diluting and mixing their own immunotherapy solutions with store-bought foods under the guidance of an experienced allergy clinic,” she added.

“Overall, evidence is building that by various routes, initial small amounts with minimal updoses, plus the tincture of time, may be preferred to multiple frequent updosing from multiple perspectives, including safety, feasibility, cost, and medical resources. It will also be important to understand the preferences and goals of the patient and family as various regimens become more available,” Dr. Upton concluded.

The study was funded by BC Children’s Hospital Foundation. Dr. Chan reported receiving research support from DVB Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi, Genzyme, Bausch Health, Avir Pharma, AstraZeneca, ALK, and Alladapt; and was a colead of the CSACI OIT guidelines. Dr. Upton reported research support/grants from Novartis, Regeneron, Sanofi, ALK Abello, DBV Technologies, CIHR, and SickKids Food Allergy and Anaphylaxis Program and fees from Pfizer, ALK Abello, Bausch Health, Astra Zeneca, and Pharming. She serves as an associate editor for Allergy, Asthma & Clinical Immunology and is on the Board of Directors of Canadian Society of Allergy and Clinical Immunology and the Healthcare Advisory Board of Food Allergy Canada.

A version of this article appeared on Medscape.com .

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Brian Rini. I’m an Ingram Professor of Medicine at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. I’m going to talk to you briefly today about some major highlights in renal cancer from the Genitourinary (GU) Cancer Symposium that was just held. I think there’s three main areas: adjuvant therapy in kidney cancer, frontline therapy in advanced disease, and the refractory space.

To open with adjuvant therapy, the biggest news in kidney cancer, and probably all of GU cancer at ASCO GU this year, was the adjuvant pembrolizumab overall survival data. This KEYNOTE study had previously shown disease-free survival advantages over placebo in a population with high-risk resected kidney cancer. There was a trend toward overall survival, but it was not significant in those early analyses.

Now with nearly 5 years of follow-up, we see an overall survival advantage, with a hazard ratio in the 0.6 range — so, about a 40% reduction in the risk for death among these patients receiving adjuvant pembrolizumab (pembro). This was really important for the field. It’s been difficult to show a survival advantage, even in diseases like melanoma, which is considered at least as much, if not more immune responsive, and I think puts into perspective whether to offer this drug to high-risk resected patients. And it certainly needs to be considered for this population.

I think the balance on that — and this came out in some of the questions after the session — was around how many of the placebo recipients got salvage immune therapy, which would be a standard of care. But in the countries where this was done, it’s not really clear how many actually got therapy. We know most patients got some salvage therapy, be it local or systemic, and about half the patients got immune therapy. But some more granular detail would be necessary.

The other thing I would mention is that this was paired with the previous presentation, which was adjuvant nivolumab. It was a very similar study, a similar drug in a similar setting, but it did not show any advantages of either disease-free or overall survival. This comes on the heels of other negative studies and a negative ipilimumab/nivolumab (ipi/nivo) study in this setting, part of the same study.

The reasons for these discrepancies are not entirely clear. There’s differences in populations and duration of therapy and mechanism, and all sorts of things. I don’t think anybody’s really been able to come up with one reason why we have some negative immune trials in kidney cancer and one shiningly positive one. But be that as it may, I think the take-home was that adjuvant pembro is certainly a standard of care in high-risk disease, and a benefit/risk discussion needs to be had with each individual patient. And I think pembro will be the building block for future studies, some of which are ongoing.

The second major area of update was in frontline kidney cancer. There weren’t a lot of new data, but there were updates to the existing trials. As you may know, frontline immune-based doublet is a standard of care in this disease: either ipi/nivo or one of the immuno-oncology/tyrosine kinase inhibitor (IO/TKI) regimens. We had two updates. One was an 8-year update on ipi/nivo. It’s a really long follow-up for these patients now, and what was observed was that these results remain remarkably consistent.

The hazard ratios for benefit in terms of survival and durability of response are really consistent over the past several years — again, a hallmark of immune therapy. Over half the responders are still responding now, many years later. I think that only strengthens the position of ipi/nivo as a choice for advanced clear cell kidney cancer patients. Again, there are good long-term toxicity data, and some patients can remain off treatment in what’s called treatment-free survival. So, an important update. We look forward to future, probably 10-year, data.

The CheckMate 9ER cabozantinib/nivolumab (cabo/nivo) study was updated now with many years of follow-up, as some of the other IO/TKI regimens have as well. And I think there is a similar theme, although a few years behind in maturity from the ipi/nivo data. It shows persistence of benefit. With IO/TKI regimens, a lot of the benefit is up front. It’s high response rates. It’s progression-free survival (PFS). But we’re starting to see some of that durability.

Where it’ll land, if there will be a tail of the curve and where it will be, is unclear, but these updates are important in terms of counseling patients. Patients want to know not just what’s going to happen at their first scan but also years from now. And they’re planning to be around years from now. So, I think these data are important.

The last thing I’ll mention is a health-related quality-of-life update from what was called the 005 trial of belzutifan, an oral HIF inhibitor, compared with everolimus. We heard data at the European Society for Medical Oncology (ESMO) Congress 2023 on a PFS and response-rate advantage. The drug was approved by the US Food and Drug Administration (FDA) in late December, and now we see some quality-of-life data.

Quality-of-life questionnaires and scales have a lot of imperfections. I don’t think they necessarily capture everything we want. But in this case, it was fairly clean in that belzutifan is known to be a well-tolerated agent. The toxicity profile is clean. It’s been used for years in patients with Von Hippel-Lindau syndrome, certainly in the trials for years, and has shown good tolerance over time. So, I view these data as complementary to what we already knew about the drug, but they’re nice to see.

It’s nice to see datasets come together and show the same thing: Not only is the drug active in a refractory renal cell carcinoma (RCC) setting, but also it’s really well tolerated and does not adversely impact patients› quality of life. I use this drug a lot in refractory kidney cancer, and because it’s so well tolerated. That means it’s also combinable. And there are some very large studies in the front-end second-line space combining it, in a space where people believe that it has more activity. But there are some complementary data as we wait for the overall survival signal, hopefully, from this regimen.

So, there have been some exciting updates, mostly in the adjuvant space but also in some other spaces in kidney cancer and building upon some of the clinical advances that we had seen from previous meetings. I’m Brian Rini, and I appreciate you attending.

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

This transcript has been edited for clarity.

Hi. I’m Brian Rini. I’m an Ingram Professor of Medicine at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. I’m going to talk to you briefly today about some major highlights in renal cancer from the Genitourinary (GU) Cancer Symposium that was just held. I think there’s three main areas: adjuvant therapy in kidney cancer, frontline therapy in advanced disease, and the refractory space.

To open with adjuvant therapy, the biggest news in kidney cancer, and probably all of GU cancer at ASCO GU this year, was the adjuvant pembrolizumab overall survival data. This KEYNOTE study had previously shown disease-free survival advantages over placebo in a population with high-risk resected kidney cancer. There was a trend toward overall survival, but it was not significant in those early analyses.

Now with nearly 5 years of follow-up, we see an overall survival advantage, with a hazard ratio in the 0.6 range — so, about a 40% reduction in the risk for death among these patients receiving adjuvant pembrolizumab (pembro). This was really important for the field. It’s been difficult to show a survival advantage, even in diseases like melanoma, which is considered at least as much, if not more immune responsive, and I think puts into perspective whether to offer this drug to high-risk resected patients. And it certainly needs to be considered for this population.

I think the balance on that — and this came out in some of the questions after the session — was around how many of the placebo recipients got salvage immune therapy, which would be a standard of care. But in the countries where this was done, it’s not really clear how many actually got therapy. We know most patients got some salvage therapy, be it local or systemic, and about half the patients got immune therapy. But some more granular detail would be necessary.

The other thing I would mention is that this was paired with the previous presentation, which was adjuvant nivolumab. It was a very similar study, a similar drug in a similar setting, but it did not show any advantages of either disease-free or overall survival. This comes on the heels of other negative studies and a negative ipilimumab/nivolumab (ipi/nivo) study in this setting, part of the same study.

The reasons for these discrepancies are not entirely clear. There’s differences in populations and duration of therapy and mechanism, and all sorts of things. I don’t think anybody’s really been able to come up with one reason why we have some negative immune trials in kidney cancer and one shiningly positive one. But be that as it may, I think the take-home was that adjuvant pembro is certainly a standard of care in high-risk disease, and a benefit/risk discussion needs to be had with each individual patient. And I think pembro will be the building block for future studies, some of which are ongoing.

The second major area of update was in frontline kidney cancer. There weren’t a lot of new data, but there were updates to the existing trials. As you may know, frontline immune-based doublet is a standard of care in this disease: either ipi/nivo or one of the immuno-oncology/tyrosine kinase inhibitor (IO/TKI) regimens. We had two updates. One was an 8-year update on ipi/nivo. It’s a really long follow-up for these patients now, and what was observed was that these results remain remarkably consistent.

The hazard ratios for benefit in terms of survival and durability of response are really consistent over the past several years — again, a hallmark of immune therapy. Over half the responders are still responding now, many years later. I think that only strengthens the position of ipi/nivo as a choice for advanced clear cell kidney cancer patients. Again, there are good long-term toxicity data, and some patients can remain off treatment in what’s called treatment-free survival. So, an important update. We look forward to future, probably 10-year, data.

The CheckMate 9ER cabozantinib/nivolumab (cabo/nivo) study was updated now with many years of follow-up, as some of the other IO/TKI regimens have as well. And I think there is a similar theme, although a few years behind in maturity from the ipi/nivo data. It shows persistence of benefit. With IO/TKI regimens, a lot of the benefit is up front. It’s high response rates. It’s progression-free survival (PFS). But we’re starting to see some of that durability.

Where it’ll land, if there will be a tail of the curve and where it will be, is unclear, but these updates are important in terms of counseling patients. Patients want to know not just what’s going to happen at their first scan but also years from now. And they’re planning to be around years from now. So, I think these data are important.

The last thing I’ll mention is a health-related quality-of-life update from what was called the 005 trial of belzutifan, an oral HIF inhibitor, compared with everolimus. We heard data at the European Society for Medical Oncology (ESMO) Congress 2023 on a PFS and response-rate advantage. The drug was approved by the US Food and Drug Administration (FDA) in late December, and now we see some quality-of-life data.

Quality-of-life questionnaires and scales have a lot of imperfections. I don’t think they necessarily capture everything we want. But in this case, it was fairly clean in that belzutifan is known to be a well-tolerated agent. The toxicity profile is clean. It’s been used for years in patients with Von Hippel-Lindau syndrome, certainly in the trials for years, and has shown good tolerance over time. So, I view these data as complementary to what we already knew about the drug, but they’re nice to see.

It’s nice to see datasets come together and show the same thing: Not only is the drug active in a refractory renal cell carcinoma (RCC) setting, but also it’s really well tolerated and does not adversely impact patients› quality of life. I use this drug a lot in refractory kidney cancer, and because it’s so well tolerated. That means it’s also combinable. And there are some very large studies in the front-end second-line space combining it, in a space where people believe that it has more activity. But there are some complementary data as we wait for the overall survival signal, hopefully, from this regimen.

So, there have been some exciting updates, mostly in the adjuvant space but also in some other spaces in kidney cancer and building upon some of the clinical advances that we had seen from previous meetings. I’m Brian Rini, and I appreciate you attending.

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

This transcript has been edited for clarity.

Hi. I’m Brian Rini. I’m an Ingram Professor of Medicine at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. I’m going to talk to you briefly today about some major highlights in renal cancer from the Genitourinary (GU) Cancer Symposium that was just held. I think there’s three main areas: adjuvant therapy in kidney cancer, frontline therapy in advanced disease, and the refractory space.

To open with adjuvant therapy, the biggest news in kidney cancer, and probably all of GU cancer at ASCO GU this year, was the adjuvant pembrolizumab overall survival data. This KEYNOTE study had previously shown disease-free survival advantages over placebo in a population with high-risk resected kidney cancer. There was a trend toward overall survival, but it was not significant in those early analyses.

Now with nearly 5 years of follow-up, we see an overall survival advantage, with a hazard ratio in the 0.6 range — so, about a 40% reduction in the risk for death among these patients receiving adjuvant pembrolizumab (pembro). This was really important for the field. It’s been difficult to show a survival advantage, even in diseases like melanoma, which is considered at least as much, if not more immune responsive, and I think puts into perspective whether to offer this drug to high-risk resected patients. And it certainly needs to be considered for this population.

I think the balance on that — and this came out in some of the questions after the session — was around how many of the placebo recipients got salvage immune therapy, which would be a standard of care. But in the countries where this was done, it’s not really clear how many actually got therapy. We know most patients got some salvage therapy, be it local or systemic, and about half the patients got immune therapy. But some more granular detail would be necessary.

The other thing I would mention is that this was paired with the previous presentation, which was adjuvant nivolumab. It was a very similar study, a similar drug in a similar setting, but it did not show any advantages of either disease-free or overall survival. This comes on the heels of other negative studies and a negative ipilimumab/nivolumab (ipi/nivo) study in this setting, part of the same study.

The reasons for these discrepancies are not entirely clear. There’s differences in populations and duration of therapy and mechanism, and all sorts of things. I don’t think anybody’s really been able to come up with one reason why we have some negative immune trials in kidney cancer and one shiningly positive one. But be that as it may, I think the take-home was that adjuvant pembro is certainly a standard of care in high-risk disease, and a benefit/risk discussion needs to be had with each individual patient. And I think pembro will be the building block for future studies, some of which are ongoing.

The second major area of update was in frontline kidney cancer. There weren’t a lot of new data, but there were updates to the existing trials. As you may know, frontline immune-based doublet is a standard of care in this disease: either ipi/nivo or one of the immuno-oncology/tyrosine kinase inhibitor (IO/TKI) regimens. We had two updates. One was an 8-year update on ipi/nivo. It’s a really long follow-up for these patients now, and what was observed was that these results remain remarkably consistent.

The hazard ratios for benefit in terms of survival and durability of response are really consistent over the past several years — again, a hallmark of immune therapy. Over half the responders are still responding now, many years later. I think that only strengthens the position of ipi/nivo as a choice for advanced clear cell kidney cancer patients. Again, there are good long-term toxicity data, and some patients can remain off treatment in what’s called treatment-free survival. So, an important update. We look forward to future, probably 10-year, data.

The CheckMate 9ER cabozantinib/nivolumab (cabo/nivo) study was updated now with many years of follow-up, as some of the other IO/TKI regimens have as well. And I think there is a similar theme, although a few years behind in maturity from the ipi/nivo data. It shows persistence of benefit. With IO/TKI regimens, a lot of the benefit is up front. It’s high response rates. It’s progression-free survival (PFS). But we’re starting to see some of that durability.

Where it’ll land, if there will be a tail of the curve and where it will be, is unclear, but these updates are important in terms of counseling patients. Patients want to know not just what’s going to happen at their first scan but also years from now. And they’re planning to be around years from now. So, I think these data are important.

The last thing I’ll mention is a health-related quality-of-life update from what was called the 005 trial of belzutifan, an oral HIF inhibitor, compared with everolimus. We heard data at the European Society for Medical Oncology (ESMO) Congress 2023 on a PFS and response-rate advantage. The drug was approved by the US Food and Drug Administration (FDA) in late December, and now we see some quality-of-life data.

Quality-of-life questionnaires and scales have a lot of imperfections. I don’t think they necessarily capture everything we want. But in this case, it was fairly clean in that belzutifan is known to be a well-tolerated agent. The toxicity profile is clean. It’s been used for years in patients with Von Hippel-Lindau syndrome, certainly in the trials for years, and has shown good tolerance over time. So, I view these data as complementary to what we already knew about the drug, but they’re nice to see.

It’s nice to see datasets come together and show the same thing: Not only is the drug active in a refractory renal cell carcinoma (RCC) setting, but also it’s really well tolerated and does not adversely impact patients› quality of life. I use this drug a lot in refractory kidney cancer, and because it’s so well tolerated. That means it’s also combinable. And there are some very large studies in the front-end second-line space combining it, in a space where people believe that it has more activity. But there are some complementary data as we wait for the overall survival signal, hopefully, from this regimen.

So, there have been some exciting updates, mostly in the adjuvant space but also in some other spaces in kidney cancer and building upon some of the clinical advances that we had seen from previous meetings. I’m Brian Rini, and I appreciate you attending.

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