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Regulatory T cell (Treg) impairment is implicated in the pathogenesis of chronic inflammatory diseases, but relatively little is known about the therapeutic potential of Treg restoration. Here we present clinical evidence for the Treg-selective interleukin-2 receptor agonist rezpegaldesleukin (REZPEG) in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557). Key inclusion criteria for AD included an Eczema Area and Severity Index (EASI) score ≥ 16 and a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and for PsO included a Psoriasis Area and Severity Index (PASI) score of ≥ 12 and a static Physician's Global Assessment (sPGA) score of ≥ 3. REZPEG is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 µg/kg or 24 µg/kg once every 2 weeks for 12 weeks, meeting the primary and secondary objectives, respectively. AD patients receiving the higher dose demonstrate an 83% improvement in EASI score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and vIGA-AD responses are maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. These exploratory clinical improvements are accompanied by sustained increases in CD25 bright Tregs. REZPEG thus represents a homeostatic approach to cutaneous disease therapy and holds clinical potential in providing long-term, treatment-free disease control., (© 2024. The Author(s).)

Background: Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients continue to experience flares and substantial clinical burden despite ongoing systemic treatment., Objectives: This study assessed the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) per its label. Week 16 primary analysis results are presented., Methods: Level Up is a phase 3b/4 global, randomized, open-label, efficacy assessor blinded study evaluating UPA vs DUPI in adolescents and adults with moderate-to-severe AD who had inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (Period 1). Patients on UPA started on 15 mg and were dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on/after Week 4, or EASI 75 on/after Week 8. The primary endpoint was simultaneous achievement of EASI 90 and WP-NRS 0/1 at Week 16. Ranked secondary endpoints included skin and itch responses at varying response levels and timepoints. Safety measures were assessed throughout the study., Results: Superior efficacy in achieving simultaneous EASI 90 and WP-NRS 0/1 response at Week 16 was demonstrated with UPA vs DUPI (19.9% vs 8.9%, respectively; p<0.0001). UPA showed superiority vs DUPI for all ranked secondary endpoints, with post-hoc analyses exhibiting higher itch response rates as early as Day 2. No new safety signals were identified during this period., Conclusion: Treatment of moderate-to-severe AD with UPA, initiated at 15 mg and dose escalated based on clinical response, demonstrated superiority vs DUPI per its label for the primary endpoint of simultaneous achievement of near complete skin clearance (EASI 90) and little to no itch (WP-NRS 0/1) at Week 16, with all ranked secondary endpoints demonstrating superiority at varying skin and itch response levels and timepoints. There were no new safety signals identified compared to the previously reported safety profiles of UPA and DUPI., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Atopic Dermatitis (AD) is associated with a number of published disparities, including those related to self-identified racial/ethnic populations. Black/African American populations in the United States experience greater AD prevalence, severity, and persistence compared to other demographic groups, such as those who self-identify as White. There is consistent evidence that healthcare, environmental, and socioeconomic factors affect the prevalence, severity, and/or persistence of AD. Additionally, because of institutional and systemic racism, these same risk factors are more prevalent in racial and ethnic minority populations. Herein, we review the underlying causes of racial/ethnic disparities in AD and potential strategies to improve AD diagnosis and disease control., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Targeted systemic immune-modulating drugs (IMDs) to treat atopic dermatitis (AD) were highly efficacious in randomized trials. Trials with limited number of subjects leave questions about their safety. We describe a data and analytics structure for the production of timely, high-quality evidence on the comparative safety of recently approved IMDs in patients with AD in clinical practice. We established a series of sequential propensity score (PS)-balanced cohorts that grow in size with each annual data refresh. Nine health outcomes of interest plus conjunctivitis as a positive tracer outcome were identified. The initial treatment comparison was dupilumab, an interleukin-4/13 inhibitor, or tralokinumab, an interleukin-13 inhibitor, versus abrocitinib/upadacitinib, both JAK inhibitors. The first analysis cycle (December 2021-February 2023) compared 269 patients initiating JAK inhibitors and 2,650 initiating IL-4/IL-13 inhibitors. Patient characteristics were well balanced after PS-matching. Outpatient infections within 180 days occurred in 18% of JAK-1 inhibitor initiators versus 12% of dupilumab/ tralokinumab initiators (RR=1.50; 0.96 to 2.33) whereas acne risks were 7% vs. 3%, respectively (RR=2.29, 0.96 to 5.46). This sequential monitoring system will produce essential knowledge on the safety of IMDs to treat AD based on its growing study size of patients observed in clinical practice., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with atopic dermatitis (AD) are at increased risk of atopic and non-atopic comorbidities. In fact, the Hanifin and Rajka criteria include allergic and infectious comorbidities as a minor criterion. Despite the well-recognized list of comorbidities, the past 15 years greatly expanded the list of recognized comorbidities of AD. This narrative review focuses on comorbidities of AD using a mnemonic, VINDICATE-P: vascular/cardiovascular, infectious, neoplastic and neurologic, degenerative, iatrogenic, congenital, atopic and autoimmune, traumatic, endocrine/metabolic, and psychiatric. The comorbidities of AD vary by age. More research is needed into the mechanisms of comorbidities and optimal screening strategies in AD patients., Competing Interests: Disclosure J.I. Silverberg has received honoraria as a consultant and/or advisory board member for Abbvie, Alamar, Aldena, Amgen, AObiome, Apollo, Arcutis, Arena, Asana, Aslan, Attovia, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristell-Meyers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant, Eli Lilly, FIDE, Galderma, GlaxoSmithKline, Incyte, Inmagene, Invea, Kiniksa, Leo Pharma, Merck, My-Or Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sandoz, Sanofi-Genzyme, Shaperon, TARGET-RWE, Teva, Union, UpToDate; speaker for Abbvie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme; institution received grants from Galderma, Incyte, Pfizer. Nanette Silverberg has received honoraria as a consultant, speaker, and/ or advisory board member for Incyte, Leo. Novan, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica Pharmaceuticals., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The longitudinal course of atopic dermatitis (AD) is heterogeneous and complex. While previously thought to be a childhood disorder, recent studies demonstrated that childhood-onset AD may take several different courses that may involve persistence into adulthood becoming a lifelong condition. Other patients only demonstrated adult-onset AD. Different factors may play a role in the timing of AD onset. Assessing the longitudinal course also involves understanding the changing temporal pattern of AD. Understanding the dynamic course of AD is important in identifying individualized treatment recommendations for patients., Competing Interests: Disclosure S. Narla is a subinvestigator for Janssen, Takeda, and Eli Lilly. J.I. Silverberg has received honoraria as a consultant and/or advisory board member for AbbVie, Afyx, Arena, Asana, BioMX, Bluefin, Bodewell, Boehringer-Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo, Luna, Menlo, Novartis, Pfizer, RAPT, Regeneron, and Sanofi; data safety monitoring committee member for Afyx, Hoth, and Morphosys; speaker for Pfizer, Regeneron, and Sanofi-Genzyme; institution received grants from Galderma, Switzerland. Funding support: Not applicable. Ethics approval: Not applicable. Consent to participate: Not applicable. Availability of data and material: Not applicable. Code availability: Not applicable., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures N.B. Silverberg has been an investigator for Avita and a speaker or consultant for Regeneron, Incyte, Verrica, Novan, Apogee, Loreal, and Primus Pharmaceuticals. J.I. Silverberg has received honoraria as a consultant and/or advisory board member for Abbvie, Alamar, Aldena, Amgen, AObiome, Apollo, Arcutis, Arena, Asana, Aslan, Attovia, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristell-Meyers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant, Eli Lilly, FIDE, Galderma, GlaxoSmithKline, Incyte, Inmagene, Invea, Kiniksa, Leo Pharma, Merck, My-Or Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sandoz, Sanofi-Genzyme, Shaperon, TARGET-RWE, Teva, Union, UpToDate; speaker for Abbvie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme.

Background: Moderate-to-severe atopic dermatitis (AD) greatly impacts children/caregivers., Objective: Evaluate the impact of treatment with dupilumab on caregiver- and patient-reported AD symptoms and quality of life (QoL) in young children., Methods: In the LIBERTY AD PRESCHOOL (randomized, placebo-controlled) study, children aged 6 months to 5 years with moderate-to-severe AD received dupilumab or placebo plus low-potency topical corticosteroids for 16 weeks. This posthoc analysis assessed the change from baseline to week 16 in caregiver-reported outcome measures of AD symptoms (eg, itch and sleep) and QoL of patients and their caregivers/families., Results: Dupilumab (n = 83) vs placebo (n = 79) provided significant improvements in caregiver-reported AD symptoms and QoL. Significant improvements were seen as early as week 4 and sustained through the end of the study. Additionally, dupilumab vs placebo provided rapid and significant improvement in QoL measures for the patients' caregivers/families., Limitations: Few patients aged <2 years; significance only reported for prespecified endpoints; Infant's Dermatitis QoL Index severity strata adopted from Children's Dermatology Life Quality Index., Conclusion: Dupilumab improved AD symptoms and QoL in patients and their caregivers/families., Competing Interests: Conflicts of interest Dr Paller is a consultant for and has received honoraria from Aegerion Pharma, Azitra, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Castle Creek Biosciences, Eli Lilly, Janssen, Krystal Biotech, LEO Pharma, Novartis, Regeneron Pharmaceuticals Inc, Sanofi, Seanergy, TWI Biotechnology, and UCB, is an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal Biotech, LEO Pharma, and UCB, and is on the data and safety monitoring boards of AbbVie, Abeona Therapeutics, Catawba Research, Galderma, and InMed Pharmaceuticals. Dr Silverberg has received honoraria as a consultant and/or advisory board member from AbbVie, Alamar Biosciences, Aldena Therapeutics, Amgen, AOBiome, Arcutis Biotherapeutics, Arena Pharmaceuticals, Asana BioSciences, Aslan Pharmaceuticals, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, Dermira, DermTech, Eli Lilly, Galderma, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Menlo Therapeutics, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix Pharma, Regeneron Pharmaceuticals Inc, Sanofi, Shaperon, Target-RWE, UNION therapeutics, and UpToDate, has received speaker fees from AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron Pharmaceuticals Inc, and Sanofi, and institution grants from Galderma, Incyte, and Pfizer. Dr Simpson has received personal fees from AbbVie, Advances in Cosmetic and Medical Dermatology Hawaii, Amgen, AOBiome, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharmaceuticals, Boehringer Ingelheim, BMS, Boston Consulting Group, Collective Acumen, CorEvitas, Dermira, Eli Lilly, Evelo Biosciences, Evidera, Excerpta Medica, Forté Biosciences, Fraunhofer, Galderma, GSK, Incyte, Janssen, Johnson & Johnson, Kyowa Kirin, LEO Pharma, Medscape, Merck, Maui Derm, MJH Life Sciences, MLG Operating, Pfizer, Physicians World, PRImE, Regeneron Pharmaceuticals Inc, Revolutionizing Atopic Dermatitis, Roivant Sciences, Sanofi, Trevi Therapeutics, Valeant, Vindico Medical Education, and WebMD, and has received grants as a principal investigator from AbbVie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Castle Creek Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Kirin, National Jewish Health, LEO Pharma, Pfizer, Regeneron Pharmaceuticals Inc, Sanofi, and Target RWE. Dr Cork is an investigator and/or consultant for AbbVie, Astellas Pharma, Boots, Dermavant, Galapagos, Galderma, Hyphens Pharma, Johnson & Johnson, LEO Pharma, L’Oréal, Menlo Therapeutics, Novartis, Oxagen, Pfizer, Procter & Gamble, Reckitt Benckiser, Regeneron Pharmaceuticals Inc, and Sanofi. Dr Arkwright is an investigator at Regeneron Pharmaceuticals Inc and LEO Pharma, and is a research grant advisor and lecturer with Sanofi. Dr Chen, Dr Bansal, and Dr Wang are employees/ shareholders of Regeneron Pharmaceuticals Inc. Dr Prescilla and Dr Marco are employees of Sanofi and may hold stock and/or stock options in the company. Dr Cork has no conflict of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors made the following disclosures: N.B.S. has been an advisor or received honoraria from Amryt, Incyte, Lilly, Regeneron/ Sanofi, and Verrica Pharmaceuticals. J.I.S. has received honoraria as a consultant and/or advisory board member for Abbvie, AObiome, Arcutis, Alamar, Amgen, Arena, Arcutis, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Cara, Castle Biosciences, Celgene, Connect Biopharma, Dermavant, Dermira, Dermtech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo Pharma, Menlo, Novartis, Optum, Pfizer, RAPT, Regeneron, Sanofi-Genzyme, Shaperon, Union; speaker for Abbvie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme; institution received grants from Galderma, Pfizer. The other authors have no conflicts of interest to disclose.

Background: Moderate-to-severe atopic dermatitis (AD) often has a profound impact on the quality of life of young children and their caregivers. One of the most burdensome symptoms reported by patients is skin pain., Methods: This post hoc analysis focuses on the impact of dupilumab treatment on skin pain in young children using data from the LIBERTY AD PRESCHOOL part B (NCT03346434), a 16-week randomized, double-blind, placebo-controlled, phase 3 study in 162 children aged 6 months to 5 years with moderate-to-severe AD receiving dupilumab or placebo, plus topical corticosteroids (TCS). Analyses were performed on the full analysis set and subgroups of patients who did not achieve an Investigator's Global Assessment score of 0 or 1 (IGA >1 subgroup), or who did not achieve a 75% improvement from baseline in the Eczema Area and Severity Index (1 and

Current dermatology residency education may be deficient in curricular topics and training related to diversity, equity, and inclusion (DEI). Integrating more DEI topics within residency curricula may improve clinical care delivered to diverse populations and improve cultural humility among trainees. The objective of this electronic Delphi (e-Delphi) study was to reach a consensus on the most important DEI topics for inclusion in dermatology residency program curricula nationwide. Sixty-one DEI-related topics were proposed by an expert panel consisting of dermatologists from the Association of Professors of Dermatology DEI subcommittee and the American Academy of Dermatology Diversity Task Force. Two rounds of anonymous electronic surveys based on a 5-point Likert scale were administered using a modified e-Delphi design. Voluntary participants including residents and academic dermatologists were self-selected after an email was sent to the Association of Professors of Dermatology listserve.

Background: Construction workers (CWs) are at risk for occupational contact dermatitis (CD) owing to workplace exposures. Objective: Determine the prevalence of occupational allergic CD and characterize common occupational allergens in CWs referred for patch testing in the United States and Canada. Methods: Retrospective cross-sectional analysis of patients patch tested by the North American Contact Dermatitis Group from 2001 to 2020. Results: Of 47,843 patch-tested patients, 681 (1.4%) were CWs. Compared with non-CWs, CWs were more likely to be male (91.0% vs 30.9%) have occupational skin disease (36.9% vs 11.4%) and have hand involvement (37.2% vs 22.5%) (all P < 0.0001). Of 681 CWs, 60.1% (411) had clinically relevant positive patch test reactions, and nearly 1/3 of CWs (128) had occupationally relevant reactions. Most common occupationally relevant allergens were potassium dichromate 0.25% pet. (30.5%, 39/128), bisphenol A epoxy resin 1% pet. (28.1%, 36/128), carba mix 3% pet. (14.8%, 19/128), cobalt (ii) chloride hexahydrate 1% pet. (14.1%, 18/128), and thiuram mix 1% pet. (14.1%, 18/128). Top sources of occupationally relevant allergens were cement/concrete/mortar (20.4%, 46/225), gloves (15.1%, 34/225), and coatings (paint/lacquer/shellac/varnish/stains) (9.8%, 22/225). Conclusions: Occupational CD in North American CWs is common. In this group, frequently identified etiological sources of occupational allergic CD included metals, epoxy resin, and rubber.

Introduction: Atopic dermatitis (AD), with its hallmark symptoms of pruritus and skin lesions, often impairs patients' quality of life. We assessed time spent with clear/almost clear skin and no/minimal itch during upadacitinib treatment versus placebo or dupilumab among patients with moderate-to-severe AD., Methods: This analysis consisted of a post hoc analysis of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 were replicate, randomized, double-blind, placebo-controlled phase 3 studies with patients randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 16 weeks. Heads Up was a head-to-head, randomized, double-blind, double-dummy, phase 3b study with patients randomized (1:1) to upadacitinib 30 mg or subcutaneous dupilumab 300 mg for 24 weeks. Skin clearance was assessed with the Eczema Area and Severity Index (EASI) at baseline, weeks 1, 2, and 4, and every 4 weeks thereafter. Itch was assessed using the Worst Pruritus Numerical Rating Scale (WP-NRS) daily over 16 weeks and every 2 weeks thereafter to week 24 in Heads Up., Results: This analysis included 1683 patients in Measure Up 1 and 2 and 673 patients in Heads Up. Through 16 weeks in Measure Up 1 and 2, patients receiving upadacitinib spent 9.8-13.4 times as many days with an EASI 90 response and 7.0-10.3 times as many days with a WP-NRS 0/1 response versus placebo. In Heads Up, patients receiving upadacitinib spent 2.0 and 1.7 times as many days through 16 and 24 weeks, respectively, with an EASI 90 response versus dupilumab. Through 16 and 24 weeks, patients receiving upadacitinib spent 3.0 and 2.6 times as many days, respectively, with a WP-NRS 0/1 response versus dupilumab., Conclusions: Patients with moderate-to-severe AD spent more time with clear/almost clear skin and no/minimal itch with upadacitinib versus placebo or dupilumab., Trial Registration: ClinicalTrials.gov identifier, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), Heads Up (NCT03738397)., (© 2024. The Author(s).)

Introduction: Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 assessed efficacy of upadacitinib 30 mg and upadacitinib 15 mg against placebo, while Heads Up assessed efficacy of upadacitinib 30 mg in a head-to-head trial against dupilumab 300 mg. A head-to-head trial of upadacitinib 15 mg against dupilumab 300 mg has not been conducted. Network meta-analysis has shown that upadacitinib 30 mg and upadacitinib 15 mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated more stringent outcomes., Methods: A population-adjusted indirect comparison was conducted using post hoc individual patient data from Measure Up 1 and 2 and Heads Up to estimate how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates. Absolute response rates at weeks 4, 16, and 24 were estimated for the following outcomes: no/minimal itch [Worst Pruritus Numerical Rating Scale (WP-NRS) score of 0/1], Eczema Area and Severity Index (EASI) score of ≤ 3 (EASI ≤ 3), 100% improvement in EASI (EASI 100), both ≥ 90% improvement in EASI (EASI 90) and WP-NRS 0/1, both EASI ≤ 3 and WP-NRS 0/1, and both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to treat population for the clinical trials, and used non-responder imputation., Results: Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg and then dupilumab. This pattern was observed at week 4, week 16, and week 24., Conclusions: For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining more stringent and composite outcomes across multiple timepoints, followed by upadacitinib 15 mg and then dupilumab 300 mg., (© 2024. The Author(s).)

Background: Tapinarof cream 1% once daily (QD), a topical aryl hydrocarbon receptor agonist, downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress., Objective: To assess tapinarof efficacy and safety in adults and children down to 2 years of age with atopic dermatitis (AD)., Methods: Eight hundred and thirteen patients were randomized to tapinarof or vehicle QD in two 8-week phase 3 trials., Results: The primary efficacy endpoint, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at Week 8, was met with statistical significance in both trials: 45.4% versus 13.9% and 46.4% versus 18.0% (tapinarof vs vehicle; both P < .0001). Significantly superior Eczema Area and Severity Index 75 (EASI75) responses were also observed with tapinarof versus vehicle at Week 8: 55.8% versus 22.9% and 59.1% versus 21.2% (both P < .0001). Rapid improvements in patient-reported pruritus were also significant with tapinarof versus vehicle. Common adverse events (≥5%) of folliculitis, headache, and nasopharyngitis were mostly mild or moderate, with lower discontinuations due to adverse events in the tapinarof groups than with vehicle., Limitations: Long-term efficacy was not assessed., Conclusion: Tapinarof demonstrated highly significant efficacy and favorable safety and tolerability in a diverse population of patients with AD down to 2 years of age., Competing Interests: Conflicts of interest Dr Silverberg has received honoraria as a consultant and/or advisory board member for AbbVie, Alamar, Aldena, Amgen, AObiome, Arcutis, Arena, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant Sciences, Inc, Dermira, Dermtech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Menlo, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, TARGET-RWE, Union, and UpToDate; speaker for AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; and institution received grants from Galderma, Incyte, and Pfizer. Dr Eichenfield has served as a consultant, advisor, or investigator for AbbVie, Amgen, Apogee, Arcutis, Aslan, Bausch, Bristol Myers Squibb, Castle Biosciences, Dermavant Sciences, Inc, Eli Lilly, Forté, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi-Genzyme, and UCB Pharma. Dr Simpson reports grants and fees for participation as a consultant and principal investigator from Eli Lilly and Company, LEO Pharma, Pfizer, and Regeneron; grants for participation as a principal investigator from Galderma and Merck & Co; and fees for consultant services from AbbVie, Boehringer Ingelheim, Dermavant Sciences, Inc, Incyte, Forte Bio, Pierre Fabre Dermo, and Sanofi-Genzyme. Dr Gold has served as a consultant, and/or has received payment for the development of educational presentations, and/or has received grants from Amgen, Arcutis, Bristol Myers Squibb, Dermavant Sciences, Inc, Eli Lilly, LEO Pharma, Ortho Dermatologics, Pfizer, and UCB Biopharma. Dr Bissonnette has served as a consultant/investigator/advisory board member for AbbVie, Alumis, Almirall, Amgen, AnaptysBio, Arcutis, Aristea, Bausch Health, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Dermavant Sciences, Inc, Eli Lilly, Escalier, Janssen, Kyowa Kirin, LEO Pharma, Nimbus, Novartis, Pfizer, Regeneron, Sienna, and UCB Biopharma; and is an employee and shareholder of Innovaderm Research. Dr Papp has served as a consultant/speaker/scientific officer/has attended advisory boards for, or received grants or honoraria from AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Evelo, Galapagos, Galderma, Genentech, Gilead, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Medimmune, Meiji Seika Pharma, Merck (MSD), Merck-Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, and UCB Biopharma. Dr Browning has served as an investigator for AbbVie, Acelyrin, Amgen, Arcutis, Dermavant, Inc, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, UCB Pharma, and Vyne; and as a speaker for Regeneron, Pfizer, and Krystal. Dr Kwong is a consultant, speaker, or principal investigator for AbbVie, Almirall, Amgen, Arcutis, Dermavant Sciences, Inc, Eli Lilly, Galderma, Incyte, L’Oréal, Novartis, Novum, Ortho, Pfizer, Regeneron/Sanofi, Sun, Verrica, and UCB Pharma. Dr Korman has served as an investigator and speaker for Abbott Labs, Genentech and Astellas; received grants and honoraria; served on the advisory board and was an investigator for Centocor; received grants and residency/fellowship program funding; and was investigator and speaker for Amgen, receiving grants and honoraria. Dr Brown, Dr Rubenstein, Dr Piscitelli, Dr Somerville, and Dr Tallman are employees of Dermavant Sciences, Inc, with stock options. Dr Hebert has received research support paid to the medical school from AbbVie, Arcutis, Dermavant Sciences, Inc, and Pfizer; and honoraria received from Alphyn, Apogee, Arcutis, Dermavant Sciences, Inc, Galderma, GSK, Incyte, LEO Pharma, Novan, Ortho Dermatologics, Pfizer, Sun Pharma, and Verrica; and from Sanofi Regeneron and Ortho Dermatologics as part of data safety monitoring boards. Dr Kircik has served as a consultant, speaker, investigator, or advisory board member for Abbott Laboratories, AbbVie, Ablynx, Aclaris, Acambis, Allergan, Inc, Almirall, Amgen, Inc, Anacor Pharmaceuticals, AnaptysBio, Arcutis Biotherapeutics, Arena Pharmaceuticals, Assos Pharmaceuticals, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Bausch Health, Berlex Laboratories (Bayer HealthCare Pharmaceuticals), Biogen Idec, BioLife, Biopelle, Bristol Myers Squibb, Boehringer Ingelheim, Breckenridge Pharma, Cassiopea SpA, Centocor, Inc, Cellceutix, Cipher Pharmaceuticals, Coherus BioSciences, Colbar LifeScience, Combinatrix, Connetics Corporation, Coria Laboratories, Dermavant Sciences, Inc, Dermira, Dermik Laboratories, Dow Pharmaceutical Sciences, Inc, Dr Reddy's Laboratories, DUSA Pharmaceuticals, Embil Pharmaceutical Co Ltd, Eli Lilly, EOS, Exeltis, Ferndale Laboratories, Inc, Ferrer, Foamix Pharmaceuticals, Galderma, Genentech, Inc, GlaxoSmithKline, Glenmark Pharmaceuticals, Healthpoint, Ltd, Idera Pharmaceuticals, Incyte, Intendis, Innocutis, Innovail, ISDIN, Johnson & Johnson, Kyowa Kirin, Laboratory Skin Care Inc, LEO Pharma, L’Oréal, 3M, Maruho Co, Ltd, Medical International Technologies, Merck, Medicis Pharmaceutical Corp., Merz Pharma, NanoBio, Novartis AG, Noven Pharmaceuticals, Nucryst Pharmaceuticals Corp, Obagi, Onset Dermatologics, Ortho Neutrogena, Pediapharma, Pfizer, Promius Pharma, PuraCap, Pharmaderm, QLT, Inc, Quinnova Pharmaceuticals, Quatrix, Regeneron, Sanofi, Serono (Merck Serono International SA), SkinMedica, Inc, Stiefel Laboratories, Inc, Sun Pharma, Taro Pharmaceutical Industries, Toler Rx, Triax Pharmaceuticals, UCB Pharma, Valeant Pharmaceuticals Intl, Warner Chilcott, XenoPort, and ZAGE., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Mentha piperita (MP; peppermint) oil has many commercial uses. Objective: To characterize the epidemiology of contact allergy to MP oil 2% petrolatum. Methods: Retrospective analysis of North American Contact Dermatitis Group data (2009-2020). Results: Of 28,128 patients tested to MP, 161 (0.6%) had an allergic reaction. Most allergic patients were female (77.0%) and/or over 40 years of age (71.4%). The most common anatomical sites of dermatitis included face (31.7%; of these, one-third specified lips), hands (17.4%), and scattered/generalized (18.6%). Nearly one-third (30.4%) of reactions were strong (++)/extreme (+++), and 80.1% were considered currently relevant. Common sources included oral hygiene preparations, foods, and lip products. Co-reaction with at least 1 of the other 19 fragrance/plant-related screening test preparations occurred in 82.6% (133/161) of MP-allergic patients, most commonly Cananga odorata oil (42.9%), fragrance mix I (41.0%), hydroperoxides of linalool (35.7%), Compositae mix (35.4%), Jasminum officinale oil (31.9%), Myroxylon pereirae (31.7%), and propolis (28.1%). Co-reaction with at least 1 of the 3 most commonly used fragrance screening allergens (fragrance mix I, fragrance mix II, and/or Myroxylon pereirae ) was 59.6%. Conclusions: Twelve-year prevalence of MP allergy was 0.6%. Approximately 40% of cases would have been missed if only fragrance screening allergens were tested.

Background: Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials., Methods: ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS-TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator's Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran-Mantel-Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov: ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349)., Findings: Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS-TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS-TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS-TCI versus placebo plus TCS-TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7-18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6-19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8-22·0], p<0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6-20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS-TCI and placebo plus TCS-TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred., Interpretation: Nemolizumab plus TCS-TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved., Funding: Galderma., Competing Interests: Declaration of interests JIS has received honoraria as a consultant or advisory board member for AbbVie, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, Aslan, Attovia, BiomX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant, Eli Lilly, Galderma, GSK, Incyte, Kiniksa, LEO Pharma, MyOr Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, and Union Therapeutics; and his institution has received grants from Galderma, Incyte, and Pfizer. AW has received grants or contracts from AbbVie, Aileens, Almirall, Amgen, Beiersdorf, Bioderma, BioProject, Bristol Myers Squibb, Chugai, Galapagos, Galderma, Glenmark, GSK, Hans Karrer, Janssen, Maruho, MedImmune, MSD, Mylan, Novartis, Pfizer, Pierre Fabre, Regeneron, Sandoz, Sanofi-Aventis, and UCB; payment or honoraria from AbbVie, Aileens, Almirall, Amgen, Beiersdorf, Bioderma, Galderma, Glenmark, LEO Pharma, L'Oreal, Maruho, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi-Aventis, and UCB; and support for attending meetings or travel from AbbVie, LEO Pharma, and Pierre Fabre. He has also participated on a data safety monitoring board or advisory board for Alentis Therapeutics and BioProject; served as Secretary and Executive Board member of the International Society of Atopic Dermatitis and Vice Chair of the European Task Force on Atopic Dermatitis; and received medical writing support for clinical trial reports from AbbVie, Almirall, Galderma, LEO Pharma, Eli Lilly, L'Oreal, Merck, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi-Aventis, and UCB. AR has served as an investigator or participated in advisory boards for AbbVie, Alvotech, Amgen, AnaptysBio, Biotherapy, Bristol Myers Squibb, Celgene, Celltrion, Dermira, Galderma, Inflarx, Janssen, Kiniksa, Kymab, LEO Pharma, Novartis, Pierre Fabre, Pfizer, Trevi Therapeutics, and UCB; and has received honoraria from Chema Rzeszow, Eli Lilly, LEO Pharma, Novartis, Sandoz, and Takeda. DT is a lecturer or consultant for AbbVie, Almirall, Amgen, Boehringer-Ingelheim, Bristol Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Eli Lilly, Novartis, Regeneron, Sandoz, Target RWE, and UCB; and has received grants from AbbVie, LEO Pharma, and Novartis (paid to his institution). FJL has received honoraria as a consultant, advisory board member, or speaker for Almirall, Celgene, Eli Lilly, Galderma, Menlo Therapeutics, Novartis, Pelpharma, Pfizer, Sanofi, Trevi Therapeutics, and Vifor Pharma; has received support for participating in scientific meetings from Amgen, AbbVie, Celgene, Eli Lilly, Galderma, Janssen-Cilag, LEO Pharma, Novartis, Pelpharma, Pfizer, and Sanofi; and has served as the principal investigator in clinical studies for Amgen, Almirall, DS Biopharma, Eli Lilly, Galderma, Incyte, Kiniksa, Menlo Therapeutics, LEO Pharma, Pfizer, and Trevi Therapeutics. KAP has served as a consultant, scientific advisor, investigator, scientific officer, or speaker for Pfizer, AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite BioPharma, Celltrion, Concert Pharmaceuticals, CorEvitas, Dermavant, Dermira, Dice Pharmaceuticals, Dice Therapeutics, Eli Lilly, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte, Janssen, Kymab, Kyowa Hakka Kirin, LEO Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Reistone, Sandoz, Genzyme (subsidiary of Sanofi Aventis), Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB, and Zai Lab. LSG has received grants, contracts, consulting fees, payment, or honoraria for scientific or educational work from Galderma, AbbVie, Pfizer, Incyte, Arcutis, LEO Pharma, Dermavan, and Eli Lilly; and is an investigator for Allergan and Galderma. J-DB has received speaker fees from AbbVie, AstraZeneca, Galderma, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Sanofi, consulting fees from Eli Lilly and Neovacs, a research grant from Astra Zeneca, Sanofi, and Therakos, and travel grants from AbbVie, Janssen, and Sanofi; and has served on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Galderma, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Sanofi. AEP has received grants or contracts from Amgen, Medac Pharma, and Pfizer, acted as an investigator, speaker, and advisor for or received educational support or research funding from Sanofi, Eli Lilly, Pfizer, LEO Pharma, AbbVie, Galderma, Novartis, Janssen, Boehringer Ingelheim, Bristol Myers Squibb, UCB, Amgen, Almirall, Artax Biopharma, and Medac Pharma. JMC has received honoraria as a consultant, advisory board member, or speaker, or has served as the principal investigator in clinical studies, for Almirall, Celgene, Eli Lilly, Galderma, Novartis, Pfizer, Sanofi, Amgen, AbbVie, Janssen-Cilag, LEO Pharma, UCB, Boehringer Ingelheim, Bristol Myers Squibb, and Sandoz. BR has served as an investigator for Galderma. JCS has received consulting fees or honoraria from Galderma, AbbVie, Almirall, Eli Lilly, Janssen, LEO Pharma, Novartis, Pierre-Fabre, Pfizer, Sanofi-Genzyme, Trevi, and UCB; has served as President of the Polish Dermatological Society; and has served as an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InflaRx, Janssen, Kliniksa, Kymab, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Trevi Therapeutics, and UCB Pharma. DK has served as an investigator for Galderma. BH is an investigator for Galderma. MK has served as an investigator for Galderma. NM is a consultant or speaker for AbbVie, Almirall, Apogee, Boehringer Ingelheim, Bristol Myers Squibb, Dr Wolff, Eli Lilly, La Roche-Posay, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB; and has served as an investigator for Galderma. SP has served as an investigator for Galderma. NN has served as an investigator for Galderma. MBS has received honoraria as a consultant, advisory board member, or speaker from Amgen, AbbVie, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Incyte Pharma, Janssen, L'Oréal Canada, LEO Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharmaceuticals, and UCB Canada; support for attending meetings or travel from Galderma, Janssen, and Pfizer; has served as the principal investigator in clinical studies for Alumis, Amgen, AbbVie, Bristol Myers Squibb, Dermavant, Evelo, Galderma, Inycte, Janssen, LEO Pharma, Meiji Pharma, Moberg Pharma, Novartis, Pfizer, Reistone Biopharma, Sanofi, and Ventyx Biosciences; and is Treasurer for the Canadian Dermatology Association, Treasurer for the Ontario Medical Association section of Dermatology, and Secretary for the Dermatology Association of Ontario. VJ has consulted or advised for or received research funding for speakers bureaus from Pediapharm, Aralez, Sanofi, Regeneron, Bausch, Novartis, Medexus, ALK-Abelló, Celgene, LEO Pharma, Mylan, Amgen, AbbVie, Pfizer, AstraZeneca, GSK, Covis Pharma, and Incyte; and has received research grants from Eli Lilly, Pfizer, Galderma, AstraZeneca, Arcutis, Sanofi, LEO Pharma, Amgen, AbbVie, GSK, Allakos, Novartis, Janssen, and Kymab. KP has served as an investigator for Galderma. SYC, PFM, LU, and CP are employees of Galderma., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Lebrikizumab is a novel monoclonal antibody with established efficacy in patients with moderate-to-severe atopic dermatitis (AD) in multiple Phase 3 trials. One of the ultimate treatment goals for patients with moderate-to-severe AD is to achieve stable disease control without concern for planning future life events., Methods: In ADvocate1 and ADvocate2, lebrikizumab-treated patients meeting the protocol-defined response criteria at Week 16 were re-randomized 2:2:1 to receive lebrikizumab every 2 weeks (Q2W), lebrikizumab every 4 weeks (Q4W), or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. In this post hoc analysis, we evaluated the proportions of patients with no or minimal fluctuations of efficacy during the 36-week maintenance period and plotted individual patient trajectories. We defined no or minimal fluctuations as achieving and maintaining the defined endpoint (≥ 75% improvement in the Eczema Area and Severity Index [EASI 75], ≥ 90% improvement in EASI, Pruritus Numeric Rating Scale [NRS] ≥ 4-point improvement, or Pruritus NRS ≥ 3-point improvement) for ≥ 80% of the study visits. If patients used rescue medication, discontinued treatment, or transferred to the escape arm, data collected at or after the event were imputed as non-response., Results: The proportions of lebrikizumab responders who maintained EASI 75 with no or minimal fluctuations were 70.8% (lebrikizumab Q2W), 71.2% (lebrikizumab Q4W), and 60.0% (lebrikizumab withdrawal). Of the patients with baseline Pruritus NRS ≥ 4 and who achieved ≥ 4-point improvement at Week 16, 66.1% (lebrikizumab Q2W), 62.7% (lebrikizumab Q4W), and 55.2% (lebrikizumab withdrawal) maintained ≥ 4-point Pruritus NRS improvement with no or minimal fluctuations., Conclusions: Patients who met the response criteria at Week 16 and continued treatment with lebrikizumab Q2W or Q4W demonstrated a stable response with no or minimal fluctuations of efficacy in measures of skin and itch up to Week 52., Clinical Trial Registration: NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2)., (© 2024. The Author(s).)

Importance: Cendakimab selectively targets interleukin (IL)-13, a type 2 cytokine implicated in atopic dermatitis (AD) pathogenesis, by inhibiting binding to its receptors (IL13R-α1 and IL13R-α2). Proof-of-concept work in AD supports using cendakimab for type 2 inflammatory diseases., Objective: To evaluate the efficacy and safety of cendakimab compared with placebo in patients with moderate to severe AD., Design, Setting, and Participants: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial was conducted from May 2021 to November 2022. Adult patients with moderate to severe AD and inadequate response to topical medications were enrolled at 69 sites in 5 countries (US [n = 26], Japan [n = 17], Canada [n = 9], Poland [n = 9], and Czech Republic [n = 8]). Data were analyzed between April 25, 2023, and October 16, 2023., Interventions: Patients were randomized (1:1:1:1) to receive subcutaneous cendakimab, 360 mg, every 2 weeks; 720 mg, every 2 weeks; 720 mg, once weekly; or placebo., Main Outcome and Measure: Mean percentage change in Eczema Area and Severity Index scores from baseline to week 16. Hierarchical testing with multiplicity adjustment was performed for 720 mg, once weekly vs placebo, then 720 mg, every 2 weeks vs placebo, and then 360 mg, every 2 weeks vs placebo., Results: Overall, 221 patients were randomized, and 220 received study drug (95 women [43%]; mean [SD] age, 37.7 [13.9] years; 720 mg, once weekly [54 (24%)]; 720 mg, every 2 weeks [55 (25%)]; 360 mg, every 2 weeks [55 (25%)]; placebo [56 (26%)]). The primary efficacy end point was met for cendakimab, 720 mg, once weekly vs placebo (-84.4 vs -62.7; P = .003) but missed statistical significance for 720 mg, every 2 weeks (-76.0 vs -62.7; P = .06). The treatment effect for 360 mg, every 2 weeks (-16.3; nominal P = .03 vs placebo) was comparable with 720 mg, once weekly (-21.8); however, significance was not claimed because the hierarchical testing sequence was interrupted. Of patients with treatment-emergent adverse events leading to discontinuation, 4 (7.4%) received 720 mg, once weekly; 2 (3.6%) 720 mg, every 2 weeks; 1 (1.8%) 360 mg, every 2 weeks; and 2 (3.6%) placebo., Conclusions and Relevance: The results of this randomized clinical trial indicated that cendakimab was effective, generally safe, and well-tolerated in patients with moderate to severe AD. The primary end point was met with a significant reduction in Eczema Area and Severity Index scores with 720 mg, once weekly at week 16. Cendakimab demonstrated progressive AD improvement at all doses during 16 weeks of treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT04800315.

Background: As the available treatments for moderate-to-severe atopic dermatitis (AD) expand, understanding patient and physician preferences becomes crucial for informed decision-making., Objective: To quantify patient and physician preferences for biologics and oral systemic AD treatment attributes., Materials and methods: We conducted a cross-sectional, online discrete choice experiment (DCE) involving 306 AD patients and 206 physicians throughout the United Kingdom and Germany. Qualitative interviews identified the key attributes for inclusion in the DCE. Each choice task comprised two hypothetical patient profiles. Data were analyzed using a random-parameters logit model., Results: Results indicated a significant emphasis on efficacy, with reducing sleep disturbance and itch ranking first and second among patients, and the reverse for physicians. Time to itch relief was the third most important efficacy attribute for both groups, but relatively more important for patients than for physicians. For both groups, the risk of eye problems was the most important safety concern of those included. Mode of administration was not of great importance compared to efficacy and safety attributes., Conclusions: Our findings suggest patients prioritize sleep disturbance, an attribute not captured in prior preference studies in AD, time to itch relief and itch. These findings emphasize the importance of addressing sleep-related issues, whilst also targeting fast itch control, to enhance patients' well-being.

Background: The decision to initiate advanced systemics in patients with atopic dermatitis (AD) is complex., Objectives: To explore disease burden and clinical characteristics of patients with moderate-to-severe AD and identify characteristics associated with initiating new systemics., Methods: Data from prospective, longitudinal, non-interventional CorEvitas AD Registry were evaluated. Differences in demographic and clinical characteristics, comorbidities, disease severity (vIGA-AD ™ ; body surface area (BSA); Eczema Area and Severity Index (EASI); SCORing AD [SCORAD]), and patient-reported outcomes (PROs) were assessed between systemic and non-systemic therapy groups., Results: Of 883 patients, 673 were newly prescribed systemics and 210 were not. Non-systemic therapy group had higher than expected rates of severe disease at enrollment based on vIGA-AD = 4 (39%), mean BSA involvement (31%), and mean EASI (19). PROs for non-systemic therapy group indicated elevated burden from AD on quality of life and poor disease control. SCORAD, peak pruritus in the past 24 h, history of biologics, and facial pallor, were significantly associated with initiation of systemics at enrollment., Conclusion: While disease burden likely influences the initiation of systemic therapy, many patients with significant burden are not treated with systemics for unclear reasons. Further research is needed to identify other factors, beyond disease severity, that influence this decision.

Background: Current treat-to-target recommendations for atopic dermatitis (AD) may not include high enough treatment targets and do not fully consider patient needs., Objective: To develop recommendations for optimized AD management, including disease severity assessments, treatment goals and targets, and guidance for treatment escalation/modification., Methods: An international group of expert dermatologists drafted a series of recommendations for AD management using insights from a global patient study and 87 expert dermatologists from 44 countries. Experts voted on recommendations using a modified eDelphi voting process., Results: The Aiming High in Eczema/Atopic Dermatitis (AHEAD) recommendations establish a novel approach to AD management, incorporating shared decision-making and a concept for minimal disease activity (MDA). Consensus (≥70% agreement) was reached for all recommendations in 1 round of voting; strong consensus (≥90% agreement) was reached for 30/34 recommendations. In the AHEAD approach, patients select their most troublesome AD feature(s); the clinician chooses a corresponding patient-reported severity measure and objective severity measure. Treatment targets are chosen from a list of 'moderate' and 'optimal' targets, with achievement of 'optimal' targets defined as MDA., Conclusions: Patient and expert insights led to the development of AHEAD recommendations, which establish a novel approach to AD management. Patients were not involved in the eDelphi voting process used to generate consensus on each recommendation. However, patient perspectives were captured in a global, qualitative patient research study that was considered by the experts in their initial drafting of the recommendations., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Treatment optimization may require dosing flexibility. The Phase 3 JADE REGIMEN trial (NCT03627767) evaluated maintenance of abrocitinib 200 mg-induced response in patients with moderate-to-severe atopic dermatitis (AD) randomly assigned to subsequent maintenance with continuous-dose abrocitinib (200 mg), reduced-dose abrocitinib (100 mg) or placebo. Maintenance with continuous-dose abrocitinib was associated with a stronger prevention of disease flares, but also with a higher occurrence of adverse events, compared with the reduced dose., Objective: This post hoc analysis of JADE REGIMEN aimed to identify predictors of not flaring during the maintenance period and to generate tools that can be used to assess probability of not flaring., Methods: Data were analysed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 mg or 100 mg) or placebo in the 40-week maintenance period. Demographic and baseline disease characteristics and level of response to induction were evaluated for association with not flaring using logistic regression. Parameters with a significant (p < 0.15) interaction with the treatment arm were fitted into a multivariable regression model, which was used to assess probability of not flaring., Results: Lower percentage body surface area affected at baseline (p = 0.09), absence of prior exposure to systemic agents (p = 0.02) and greater percentage change in EASI from baseline to randomization (p < 0.001) were identified as predictors of not flaring with abrocitinib. In both abrocitinib arms, percentage change in EASI from baseline to end of induction (Week 12) was the major contributor to the probability of not flaring in the maintenance period., Conclusions: Maintenance of response using reduced-dose abrocitinib 100 mg may be feasible for patients with lower baseline disease severity and strong response to abrocitinib 200 mg induction treatment., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Patient-focused approaches to capturing day-to-day variability in sleep disturbance are needed to properly evaluate the sleep benefits of new treatments. Such approaches rely on patient-reported outcome (PRO) measures validated in the target patient population., Methods: Using atopic dermatitis (AD) as an example of a disease in which sleep is commonly disturbed, we developed a strategy for measuring sleep disturbance in AD trials. In developing this strategy, we conducted a targeted literature review and held concept elicitation interviews with adolescents and adults with AD. We subsequently identified potentially suitable PRO measures and cognitively debriefed them. Finally, we evaluated their psychometric properties using data from phase 2b (NCT03100344) and phase 3 (NCT03985943 and NCT03989349) clinical trials., Results: The literature review confirmed that sleep disturbance is a key impact of AD but failed to identify validated PRO measures for assessing fluctuations in sleep disturbance. Subsequent concept elicitation interviews confirmed the multidimensional nature of sleep disturbance in AD and supported use of a single-item measure to assess overall sleep disturbance severity, complemented by a diary to capture individual components of sleep disturbance. The single-item sleep disturbance numerical rating scale (SD NRS) and multi-item Subject Sleep Diary (SSD)-an AD-adapted version of the Consensus Sleep Diary-were identified as potentially suitable PRO measures. Cognitive debriefing of the SD NRS and SSD demonstrated their content validity and their understandability to patients. Psychometric analyses based on AD trial data showed that the SD NRS is a well-defined, reliable, and fit-for-purpose measure of sleep disturbance in adults with AD. Furthermore, the SD NRS correlated with many SSD sleep parameters, suggesting that most concepts from the SSD can be covered using the SD NRS., Conclusions: Using these findings, we developed an approach for measuring sleep disturbance in AD trials. Subject to further research, the same approach could also be applied to future trials of other skin diseases where itch causes sleep disturbance., (© 2024. The Author(s).)

Background: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile., Objective: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program., Methods: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed., Results: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 10 3 /mm 3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1])., Conclusions: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] CLINICAL TRIAL REGISTRATION: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026)., (© 2024. The Author(s).)

Loss-of-function (LoF) mutations in the filaggrin gene (FLG) constitute the strongest genetic risk for atopic dermatitis (AD). A latitude-dependent difference in the prevalence of LoF FLG mutations was systematically evaluated. A systematic review and meta-analysis were performed to estimate the prevalence of LoF FLG mutations in AD patients and the general population by geography and ethnicity. Risk of bias was assessed by Newcastle-Ottawa Scale and Jadad score. StatsDirect, version 3 software was used to calculate all outcomes. PubMed and EMBASE were searched until 9 th  December 2021. Studies were included if they contained data on the prevalence of LoF FLG mutations in AD patients or from the general population or associations between AD and LoF FLG mutations and were authored in English. Overall, 248 studies and 229 310 AD patients and individuals of the general population were included in the quantitative analysis. The prevalence of LoF FLG mutations was 19.1% (95% CI, 17.3-21.0) in AD patients and 5.8% (95% CI, 5.3-6.2) in the general population. There was a significant positive association between AD and LoF FLG mutations in all latitudes in the Northern hemisphere, but not in all ethnicities. The prevalence of LoF FLG mutations became gradually more prevalent in populations residing farther north of the Equator but was negligible in Middle Easterners and absent in most African populations. FLG LoF mutations are common and tend to increase with northern latitude, suggesting potential clinical implications for future AD management. The existence of possible genetic fitness from FLG LoF mutations remains unknown., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Atopic dermatitis (AD), a highly pruritic, inflammatory skin disease, affects approximately 7% of adolescents globally. A topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated safety and efficacy among adolescents/adults in two phase 3 studies (TRuE-AD1/TRuE-AD2)., Objective: To describe safety and efficacy of 1.5% ruxolitinib cream versus vehicle and long-term disease control of ruxolitinib cream among adolescents aged 12-17 years from pooled phase 3 study data., Methods: Patients [≥ 12 years old with AD for ≥ 2 years, Investigator's Global Assessment score (IGA) 2/3, and 3-20% affected body surface area (BSA) at baseline] were randomized 2:2:1 to ruxolitinib cream (0.75%/1.5%) or vehicle for 8 weeks of continuous use followed by a long-term safety (LTS) period up to 52 weeks with as-needed use. Patients originally applying vehicle were rerandomized 1:1 to 0.75%/1.5% ruxolitinib cream. Efficacy measures at week 8 included IGA treatment success (IGA-TS; i.e., score of 0/1 with ≥ 2 grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), and ≥ 4-point improvement in itch numerical rating scale (NRS4). Measures of disease control during the LTS period included IGA score of 0 (clear) or 1 (almost clear) and percentage affected BSA. Safety was assessed throughout the study., Results: Of 1249 randomized patients, 245 (19.6%) were aged 12-17 years. Of these, 45 patients were randomized to vehicle and 92 patients to 1.5% ruxolitinib cream. A total of 104/137 (75.9%) patients continued on 1.5% ruxolitinib cream in the LTS period [82/92 (89.1%) continued on 1.5% ruxolitinib cream; 22/45 (48.9%) patients on vehicle were reassigned to 1.5% ruxolitinib cream], and 83/104 (79.8%) of these patients completed the LTS period. At week 8, substantially more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (50.6% versus 14.0%), EASI-75 (60.9% versus 34.9%), and NRS4 (52.1% versus 17.4%; P = 0.009). The mean (SD) reduction in itch NRS scores was significantly greater in patients applying 1.5% ruxolitinib cream versus vehicle from day 2 [- 0.9 (1.9) versus -0.2 (1.4); P = 0.03]. During the LTS period, mean (SD) trough steady-state ruxolitinib plasma concentrations at weeks 12/52 were 27.2 (55.7)/15.5 (31.5) nM. The percentage of patients achieving IGA score of 0 or 1 was sustained or further increased with 1.5% ruxolitinib cream; mean affected BSA was generally low (< 3%; i.e., mild disease). Through 52 weeks, application site reactions occurred in 1.8% of adolescent patients applying 1.5% ruxolitinib cream at any time; no patients had serious adverse events. There were no serious infections, malignancies, major adverse cardiovascular events, or thromboembolic events., Conclusions: Meaningful anti-inflammatory and antipruritic effects were demonstrated with 1.5% ruxolitinib cream in the subset of adolescent patients with AD, comparable with those observed in the overall study population; long-term, as-needed use maintained disease control and was well tolerated., Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03745638 (registered 19 November 2018) and NCT03745651 (registered 19 November 2018)., (© 2024. The Author(s).)

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that has wide-ranging roles, including regulation of inflammation and homeostasis. AhR is not a cell surface receptor; rather, it exists in a cytoplasmic complex that responds to a wide variety of structurally dissimilar endogenous, microbial, and environmental ligands. The ubiquitous expression of AhR, its ability to be activated by a wide range of ligands, and its capacity to act as a master regulator for gene expression and homeostasis make it a promising new therapeutic target. Clinical trials of tapinarof cream have now validated AhR agonism as a therapeutic approach that can deliver significant efficacy for treating inflammatory skin diseases, including psoriasis and atopic dermatitis. Tapinarof 1% cream is a first-in-class, nonsteroidal, topical, AhR agonist with a pharmacokinetic profile that results in localized exposure at sites of disease, avoiding systemic safety concerns, drug interactions, or off-target effects. Psoriasis and atopic dermatitis both involve epidermal inflammation, cellular immune responses, dysregulation of skin barrier protein expression, and oxidative stress. On the basis of the clinical effectiveness of tapinarof cream for treating inflammatory skin diseases, we review how targeting AhR may offer a significant opportunity in other conditions that share key aspects of pathogenesis, including asthma, inflammatory bowel disease, eosinophilic esophagitis, ophthalmic, and nervous system diseases., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Early prediction of abrocitinib efficacy in atopic dermatitis (AD) could help identify candidates for an early dose increase. A predictive model determined week 12 efficacy based on week 4 responses in patients receiving abrocitinib 100 mg/day and assessed the effect of an abrocitinib dose increase on platelet counts., Methods: Analysis included the phase 3 trials JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470), and TEEN (NCT03796676). For platelet counts and simulations, a phase 2 psoriasis trial (NCT02201524) and phase 2b (NCT02780167) and phase 3 (MONO-1, MONO-2, and REGIMEN (NCT03627767)) abrocitinib trials were pooled. A training-and-validation framework assessed potential predictors of response at week 4: score and score change from baseline in the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and Peak Pruritus Numerical Rating Scale (PP-NRS), and percentage change from baseline in EASI. The dependent variables at week 12 were ≥ 75% improvement in EASI (EASI-75) and IGA score of 0 (clear) or 1 (almost clear) and ≥ 2-point improvement from baseline. The probability of each variable to predict week 12 EASI-75 and IGA responses was calculated., Results: In the training cohort (n = 453), 72% of the ≥ 50% improvement in EASI (EASI-50) at week 4 responders and 16% of the nonresponders with abrocitinib 100 mg achieved EASI-75 at week 12; 48% and 6% of the week 4 EASI-50 responders and nonresponders, respectively, achieved week 12 IGA response. Similar results occurred with week 4 IGA = 2, ≥ 4-point improvement from baseline in PP-NRS, or EASI = 8 responders/nonresponders. Platelet counts after an abrocitinib dose increase from 100 to 200 mg were similar to those seen with continuous dosing with abrocitinib 100 mg or 200 mg., Conclusion: Achieving week 4 clinical responses with abrocitinib 100 mg may be useful in predicting week 12 responses. Week 4 nonresponders may benefit from a dose increase to abrocitinib 200 mg, and those that receive this dose increase are likely to achieve treatment success at week 12, with no significant impact on platelet count recovery. Video abstract available for this article., Clinical Trial Registration: NCT03349060, NCT03575871, NCT03720470, NCT03796676, NCT02201524, NCT02780167 and NCT03627767., (© 2024. The Author(s).)

The objective was to study a large, international, ethnically diverse population of patients with atopic dermatitis (AD) to support the creation of patient-centric recommendations for AD management. Qualitative data were generated from 45-min, 1:1 telephone interviews conducted across 15 countries in each patient's native language. Interviews explored the impact of AD on patients' lives, patients' most important symptoms, treatment expectations, and treatment decision-making. Participants were also questioned on their current knowledge of AD scoring systems and what was most important to include in these tools. In total, 88 adult patients (≥ 18 years old) receiving treatment for AD were recruited through a market research database, clinician referrals, and local advertising. All patients were screened to ensure a balanced and diverse sample in terms of age, gender, educational level, employment status, geographic location, and AD severity. Patients involved in market research or activities supporting advocacy groups within the previous 6 months or affiliated with or employed by pharmaceutical companies were excluded. AD had a substantial impact on patients' lives. Itch, skin redness, and dry/flaky skin were the most frequently reported symptoms, with > 75% of patients experiencing these symptoms every 1-3 days. Mental health issues were common and resulted in the greatest negative impact on patients' daily lives. Patients perceived clinicians to underestimate the burden of their AD. Patients had little awareness of AD scoring systems and indicated a preference for these to be more clearly incorporated in clinical practice. For an ideal scoring system, patients favored using a combination of patient-reported and clinician-reported outcomes to reflect disease burden and ensure consistency across all settings. This global study generated diverse patient perspectives on the disease burden of AD, their expectations of treatment, and their views on AD scoring methods. These data provide evidence to support the development of patient-centric recommendations for AD management., (© 2024. The Author(s).)

Background: Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited., Objectives: To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet., Methods: In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep., Results: A total of 133 patients (adults = 106, adolescents = 27) were randomized to dupilumab (n = 67) or placebo (n = 66). At week 16, significantly more patients receiving dupilumab (n = 27) than placebo (n = 11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P = .003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile., Limitations: Short-term, 16-week treatment period., Conclusion: Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition., Competing Interests: Conflicts of interest Dr Simpson has received personal fees from AbbVie, Advances in Cosmetic and Medical Dermatology Hawaii, Amgen, AOBiome, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharmaceuticals, BenevolentAI Bio Limited, BiomX Ltd., Bluefin Biomedicine, Boehringer Ingelheim, Boston Consulting Group, BMS, Castle Biosciences, Collective Acumen, CorEvitas, Coronado Biosciences, Dermira, Eli Lilly and Company, Evelo Biosciences, Evidera, Excerpta Medica B.V., FIDE, Forté Biosciences, Fraunhofer, Gesselschaft Z, Gilead Sciences., Galderma, GSK, Incyte, Innovaderm Research Inc., Janssen, Johnson & Johnson, Kyowa Kirin, LEO Pharma, Medscape, Merck, Maui Derm, Med Learning Group, Medscape, Merck, MJH Life Sciences, MLG Operating, Ortho Dermatologics, Pfizer, Physicians World, Pierre Fabre, PRImE, Recludix Pharm, Regeneron Pharmaceuticals Inc., Revolutionizing Atopic Dermatitis, Roivant Sciences, Sanofi, Trevi Therapeutics, Valeant, Vindico Medical Education, and WebMD; he has received grants from and/or is Principal Investigator for AbbVie, Amgen, Acrotech Biopharma Inc., Arcutis Biotherapeutics, Aslan Pharmaceuticals, Castle Creek Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Kymab, Kyowa Kirin, Merck, LEO Pharma, National Jewish Health, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Sanofi, and Target RWE. Dr Silverberg is a consultant and/or has received grants/honoraria from AbbVie, Aldena Therapeutics, Amgen, AOBiome, Arcutis, Arena Pharmaceuticals, AnaptysBio, Asana BioSciences, ASLAN Pharmaceuticals, Attovia Therapeutics, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Cara Therapeutics, Castle Biosciences, Celgene, Connect Biopharma, Corrona, Dermavant Sciences, Eli Lilly, Galderma, Glenmark, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Maui Derm, MedImmune, Menlo Therapeutics, Novartis, Optum, Pfizer, PuriCore, RAPT Therapeutics, Regeneron Pharmaceuticals Inc., Sanofi, Shaperon, Target Pharma, and Union Therapeutics. Dr Worm is an advisory board member and/or has received consulting fees from AbbVie, Aimmune Therapeutics UK, Amgen, ALK-Abelló Arzneimittel, AstraZeneca, Boehringer Ingelheim, DBV Technologies S.A., Eli Lilly, GSK, Kymab, LEO Pharma, Mylan Germany, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi. Dr Honari has received research funding from Nipera, Regeneron Pharmaceuticals Inc., and is a consultant for Biolinq, and Myesontooth. Dr Masuda is a speaker for Eli Lilly Japan K.K., Maruho Co., Ltd, Mitsubishi Tanabi Pharma Corporantion and Sanofi, and an investigator for Eli Lilly Japan K.K. Dr Syguła has no conflict of interest to disclose. Dr Schuttelaar is an advisor, consultant, speaker and/or investigator for AbbVie, Pfizer, LEO Pharma, Regeneron, Sanofi Genzyme, Eli Lilly, Galderma, and Amgen; she has received grants from Regeneron, Sanofi Genzyme, Novartis and Pfizer. Drs Mortensen, Akinlade, Maloney, Paleczny, Delevry, Xiao and Bansal are employees and shareholders of Regeneron Pharmaceuticals Inc. Drs Laws, Patel and Dubost-Brama are employees of Sanofi, and may hold stock and/or stock options in the company., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Asthma is one of the most well-recognized comorbidities of atopic dermatitis (AD). However, the relationship of AD severity and morphology with asthma characteristics in adults is not well defined., Objectives: To understand associations of AD severity and morphology with comorbid asthma age-of-onset and control in adults with AD., Methods: A cross-sectional, dermatology practice-based study was performed in adults (≥ 18 years) with AD and history of asthma (N = 252). Self-administered electronic questionnaires were completed by patients, including demographics, patient-reported outcomes measures of AD severity, history of asthma, age-of-onset, and Asthma Control Test (ACT). Multivariable logistic regression models were constructed to examine relationships between AD severity and morphology with asthma age-of-onset and control., Results: The mean ± standard deviation ACT score was 21.7 ± 4.3 (range 5-25), with 55 (21.8%) having ACT scores ≤ 19 indicating poorly controlled asthma. AD severity and morphology were not associated with adult-onset asthma or poor asthma control., Conclusions: AD severity and morphology were not consistently associated with comorbid asthma age-of-onset or control in adults with AD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Few large-scale international studies have broadly characterized the burden of atopic dermatitis (AD) across age groups among children and adolescents., Objectives: To better characterize the AD burden in paediatric patients by disease severity., Methods: This cross-sectional, web-based survey of paediatric patients (6 months to < 18 years old) was conducted in 18 countries representing North America, Latin America, Europe, Middle East/Eurasia and East Asia. Patients with diagnosed AD were identified based on the International Study of Asthma and Allergies in Childhood criteria and self-/parent-report of ever being told by a physician that they or their child had eczema. AD severity was assessed using the Patient-Oriented Eczema Measure and Patient Global Assessment. Outcomes included measures of itch, skin pain, sleep, health-related quality of life (HRQoL), missed school days and atopic comorbidities., Results: The survey included 1489 children aged 6 months to < 6 years; 2898 children aged 6 to < 12 years; and 3078 adolescents aged 12 to < 18 years diagnosed with AD. Although the burden of mild AD was substantial, paediatric patients with moderate or severe AD had more itch, skin pain, sleep problems and impaired HRQoL, and missed more school days relative to those with mild AD; greater burden was observed among those with severe relative to moderate AD. At least one atopic comorbidity was present in 92.5% of all respondents., Conclusions: These results highlight the burden of AD in paediatric patients, especially those with moderate-to-severe disease, and suggest the need for assessments that include the impact of AD on function and daily life., Competing Interests: Conflicts of interest A full list of the authors’ conflicts of interest is available in Appendix S1 (see Supporting Information)., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

A treat-to-target approach was recently developed to guide systemic treatment for adults with atopic dermatitis (AD). Recommendations outlined criteria for a 3-month initial acceptable treatment target and a 6-month optimal target, evaluated using global assessment of patient-reported disease severity, as well as Eczema Area and Severity Index, itch assessed on an 11-point numerical rating scale, Dermatology Life Quality Index, or Patient-Oriented Eczema Measure. Achievement of these targets with once-daily upadacitinib (15 mg and 30 mg) monotherapy was evaluated using integrated adult data from the Measure Up 1 and 2 phase 3 studies. Among the 852 patients treated with upadacitinib 15 mg or 30 mg, the 3-month initial acceptable target was achieved by >80%, >78%, and ≥87% of patients, and the 6-month optimal target was achieved by ≥53%, >61%, and >73% of patients at weeks 2, 16, and 52, respectively. Achievement of all 6 individual criteria for each of the target goals also increased over time. These findings suggest that upadacitinib 15 mg and 30 mg may help improve standards of care in patients with moderate-to-severe AD by achieving 6-month target goals at 16 weeks and as early as 2 weeks for most patients.

Background: Patients with atopic dermatitis (AD) exhibit heterogeneous clinical phenotypes, reflecting different combinations of itch and lesional severity. AD with severe itch but clear-moderate lesions, also known as itch-dominant AD, is a common clinical phenotype., Objectives: To evaluate abrocitinib efficacy in patients with moderate-to-severe AD who have itch-dominant AD., Methods: This post hoc analysis includes pooled data from clinical trials of patients with moderate-to-severe AD receiving abrocitinib (100 or 200 mg) as monotherapy (phase 2b; phase 3 JADE MONO-1 and JADE MONO-2) or in combination with topical therapy (phase 3 JADE COMPARE). Data from the ongoing long-term JADE EXTEND trial (data cutoff April 2020) were also evaluated. Itch-dominant AD was defined as baseline Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7-10 and Investigator's Global Assessment of 0-3 or Eczema Area and Severity Index of 0‒21. Assessments included a ≥4-point improvement in PP-NRS (PP-NRS4), PP-NRS score of 0 (no itch) or 1 (little itch) in patients with PP-NRS score ≥2 at baseline, ≥4-point improvement from baseline in Patient-Oriented Eczema Measure (POEM-4), Patient Global Assessment (PtGA) of clear or almost clear, and Dermatology Life Quality Index (DLQI) score of 0 or 1 (no impact or little impact of AD on quality of life [QoL])., Results: In the pooled monotherapy trials, 37% of patients had itch-dominant AD at baseline. As early as Week 2, more patients with itch-dominant AD achieved PP-NRS4 with abrocitinib 100 mg (35%) and abrocitinib 200 mg (57%) versus placebo (7%); 6% and 22% versus 0%, respectively, achieved PP-NRS 0/1. More patients achieved a PtGA of clear/almost clear at Week 12 with abrocitinib 100 mg (28%) and abrocitinib 200 mg (45%) than placebo (9%). Additionally, abrocitinib led to clinically meaningful improvements in POEM and DLQI. Most patients with itch-dominant AD experienced itch improvement over time with abrocitinib monotherapy or with concomitant topical therapy; 86%-87% and 62%-67% of patients had no itch-moderate itch and clear-moderate lesions by weeks 24 and 48, respectively., Conclusions: Abrocitinib is highly efficacious in patients with itch-dominant AD, demonstrating rapid, deep, and sustained improvements in itch and clinically meaningful improvements in patients' QoL., Trial Registration Numbers: NCT02780167; NCT03349060; NCT03575871; NCT03720470; NCT03422822., Competing Interests: J.I.S has served as an investigator for Celgene, Eli Lilly and Company, F. Hoffmann‐LaRoche, Menlo Therapeutics, Realm Therapeutics, Regeneron Pharmaceuticals, and Sanofi‐Genzyme, as a consultant for Pfizer Inc., AbbVie, Anacor, AnaptysBio, Arena Pharmaceuticals, Dermavant, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Menlo Therapeutics, Novartis, Realm Therapeutics, Regeneron Pharmaceuticals, and Sanofi‐Genzyme, and as a speaker for Regeneron Pharmaceuticals and Sanofi‐Genzyme. J.P.T is an employee of LEO pharma, and served as an advisor for Pfizer Inc., AbbVie, Almirall, Arena Pharmaceuticals, Aslan Pharmaceuticals, Coloplast, Eli Lilly and Company, LEO Pharma, OM Pharma, Union Therapeutics, Regeneron Pharmaceuticals, and Sanofi‐Genzyme, a speaker for Pfizer Inc., AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Regeneron Pharmaceuticals, and Sanofi‐Genzyme, and received research grants from Pfizer Inc., Regeneron Pharmaceuticals, and Sanofi‐Genzyme. I.L is an employee of IQVIA, who were paid contractors to Pfizer Inc. in the development of this manuscript and in providing statistical support. D.E.M, and E.G are employees and shareholders of Pfizer Inc. R.C has served as an advisory board member, consultant, and/or investigator for Pfizer Inc., AbbVie, Apogee, Arcutis, Arena, Argenx, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, Eli Lilly and Company, EPI Health, Incyte, LEO Pharma, L’Oréal, National Eczema Association, Regeneron Pharmaceuticals, Sanofi‐Genzyme, and UCB, and as a speaker for Pfizer Inc., AbbVie, Arcutis, Beiersdorf, Dermavant, Eli Lilly and Company, EPI Health, Incyte, LEO Pharma, Regeneron Pharmaceuticals, Sanofi‐Genzyme, and UCB., (© 2024 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Competing Interests: Dr N. B. Silverberg has been an adviser or received honoraria from Amryt, Incyte, Lilly, Regeneron/Sanofi, and Verrica Pharmaceuticals. Dr J. I. Silverberg has received honoraria as a consultant and/or advisory board member for AbbVie, AOBiome, Arcutis, Alamar, Amgen, Arena, Arcutis, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer Ingelheim, Cara, Castle Biosciences, Celgene, Connect Biopharma, Dermavant, Dermira, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo Pharma, Menlo, Novartis, Optum, Pfizer, RAPT, Regeneron, Sanofi-Genzyme, Shaperon, and Union, speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, and institution received grants from Galderma and Pfizer. The other authors have no conflicts of interest to declare.

Background: Allergic contact Dermatitis® (ACD) in older adults (OA) represents a significant health burden, but few studies examine the prevalence and characteristics of contact allergy and ACD in this population. Objective: To compare positive and clinically relevant patch test results in OA versus younger adults (YA) and children. Methods: Retrospective analysis of patch test results obtained in OA (≥65 years), YA (19-64 years), and children (≤18 years) by the North American Contact Dermatitis® Group, 2009 to 2020. Results: Of 28,177 patients patch tested, 5366 (19.0%) were OA. OA were more likely to have a final primary diagnosis of ACD as compared with YA (50.8% vs 49.2%, P  = 0.035) and children (44.6%, P  < 0.0001). The primary site of Dermatitis® also differed by age group, with OA having a higher proportion of Dermatitis® affecting the trunk, scalp, anogenital region, and "under clothing," and a lower proportion of Dermatitis® affecting the face, lips, and feet. Limitations: Retrospective design, lack of follow-up, and referral population. Conclusion: OA were as likely and were statistically even more likely to have a final primary diagnosis of ACD compared with YA and children. Anatomic site of Dermatitis® also differed by age group. This underscores the need for patch testing in OA when ACD is suspected.

Background: In patients with moderate-to-severe atopic Dermatitis® (AD), greater skin clearance and itch reduction are associated with more pronounced improvements in quality of life (QoL). Objective : To characterize the aggregate response benefit with upadacitinib versus dupilumab or placebo in patients with moderate-to-severe AD. Methods : Degree of skin clearance and itch response in 3 phase 3 studies (Heads Up [NCT03738397] and Measure Up 1/2 [integrated; NCT03569293/NCT03607422]) were assessed by the Eczema Area and Severity Index (EASI) and Worst Pruritus Numerical Rating Scale (WP-NRS), respectively, using mutually exclusive categories. The aggregate response benefit with upadacitinib over dupilumab or placebo was determined by summing incremental differences for each EASI or WP-NRS category across the full distribution of patient responses. Results : Comparisons across EASI improvement threshold distributions, EASI severity levels, and WP-NRS categories demonstrated an aggregate response benefit favoring upadacitinib over dupilumab as early as week 4 and continuing at weeks 16 and 24. Similar trends were observed for upadacitinib 15 and 30 mg versus placebo. Conclusions : The aggregate response benefit in skin clearance and itch reduction favored upadacitinib 30 mg over dupilumab and upadacitinib 15 or 30 mg over placebo. These benefits may translate to overall greater improvements in patient QoL.

Introduction: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks., Methods: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment)., Results: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1-2 weeks), increased through weeks 4-6, and were maintained through week 16., Conclusions: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD., Trial Registration: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422., (© 2024. The Author(s).)

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis., Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis., Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16., Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes., Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52., Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018)., (© 2024. The Author(s).)