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Introduction: Patients with atopic dermatitis (AD) often have other comorbid type 2 inflammatory conditions. The aim of this study was to evaluate the impact of type 2 comorbidities on the response to and safety of dupilumab in young children with AD., Methods: LIBERTY AD PRESCHOOL part B was a randomized, placebo-controlled trial in children aged 6 months to 5 years with moderate-to-severe AD. In this post hoc analysis, patients were stratified by the presence or absence of caregiver-reported selected type 2 comorbidities at baseline: asthma, allergic rhinitis (AR), and food allergies (FAs)., Results: At week 16, significantly more patients receiving dupilumab versus placebo, with or without asthma and AR, achieved an Investigator's Global Assessment (IGA) score of 0/1 and a ≥ 75% improvement in Eczema Area and Severity Index (all p < 0.05). Significantly more patients receiving dupilumab versus placebo with FAs and numerically more patients without FAs achieved an IGA score of 0/1 (p = 0.0007 and p = 0.06). Numerically more patients receiving dupilumab versus placebo with asthma and significantly more patients without asthma achieved a ≥ 4-point reduction in the weekly average of daily score on the Worst Scratch/Itch Numeric Rating Scale (WSI-NRS) (p = 0.6 and p < 0.0001). Additionally, significantly more patients receiving dupilumab versus placebo with or without AR (p = 0.008 and p < 0.0001) and with or without FAs (p = 0.0002 and p = 0.004) achieved a ≥ 4-point reduction in the weekly average of daily score on the WSI-NRS. Overall safety was consistent with the known dupilumab safety profile., Conclusions: Dupilumab treatment improves AD signs and symptoms in children aged 6 months to 5 years with and without type 2 comorbidities such as asthma, AR, and FAs., Trial Registration: ClinicalTrials.gov registration number NCT03346434., Infographic: Do type 2 comorbidities impact the response to dupilumab in children with atopic dermatitis? (MP4 103,451 KB)., (© 2024. The Author(s).)

Background: Atopic dermatitis (AD) is associated with itch, skin pain, sleep disturbances, and diminished quality of life (QoL). Ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream demonstrated efficacy and safety in adults and adolescents with mild-to-moderate AD in two phase III studies (TRuE-AD1/TRuE-AD2). In TRuE-AD1/TRuE-AD2, significant improvements in itch were observed as early as 12 h following application of ruxolitinib cream., Objective: The aim of this paper was to assess additional patient-reported outcomes (PROs) in the vehicle-controlled (VC) and long-term safety (LTS) periods of TRuE-AD1/TRuE-AD2., Methods: In the TRuE-AD studies, patients aged ≥12 years with AD were randomized 2:2:1 to apply twice-daily 1.5% ruxolitinib cream, 0.75% ruxolitinib cream, or vehicle cream continuously for 8 weeks (VC period). During the LTS period, patients applied the same ruxolitinib cream strength, but on an as-needed basis; patients who initially applied vehicle were re-randomized to apply 0.75% or 1.5% ruxolitinib cream. Pooled data from both study periods were analyzed. PRO assessments included symptoms (itch [Patient-Oriented Eczema Measure, POEM], skin pain [numerical rating scale], and sleep [POEM and Patient-Reported Outcomes Measurement Information System]) and assessments of disease-specific QoL (Dermatology Life Quality Index [DLQI] and the children's version [CDLQI])., Results: A total of 1208 and 1031 patients from the VC and LTS periods, respectively, were included in the analysis. Significant improvements in skin pain were observed within 12 h among patients who applied ruxolitinib cream versus vehicle; improvements continued throughout the VC period. Improvements in patient-reported symptoms (including sleep) were observed within 2 weeks (first assessment) of ruxolitinib cream application. At Week 2, significant improvements in symptom burden and overall QoL were observed with ruxolitinib cream (0.75%/1.5%) versus vehicle in POEM (-8.9/-9.8 vs -2.2; both p < 0.0001), DLQI (mean changes from baseline, -5.8/-6.1 vs -1.2; both p < 0.0001), and CDLQI (-4.3/-5.3 vs -1.3; both p < 0.0001). Further symptom burden and QoL improvements were reported during the VC period and were maintained through the end of the LTS period (Week 52)., Conclusions: Consistent with the previously reported itch response data, ruxolitinib cream improved skin pain within 12 h of application. Ruxolitinib cream improved patient-reported AD symptom burden and overall QoL by Week 2. Improvements continued or were maintained for 52 weeks. (Graphical abstract and plain language summary available)., Trial Registration: ClinicalTrials.gov identifiers, NCT03745638 and NCT03745651 (both studies were registered on November 19, 2018)., Competing Interests: Declarations Funding This study was funded by Incyte Corporation (Wilmington, DE, USA). Competing Interests ELS has served as an investigator for AbbVie, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, Merck, Pfizer, and Regeneron and as a consultant with honoraria for AbbVie, Eli Lilly, Forte, Galderma, Incyte Corporation, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, and Valeant. MA has served as a consultant, researcher, and/or has received research grants from AbbVie, Almirall, Amgen, Bayer, Beiersdorf, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Centocor, Dermira, Eli Lilly, Galderma, Genzyme, GlaxoSmithKline, Hexal, Incyte Corporation, Janssen, LEO Pharma, Medac, Menlo Therapeutics, MSD, Novartis, Pfizer, Regeneron, Sandoz, Sanofi, Stallergenes, Takeda, Trevi, and UCB. DT has served as an investigator and/or consultant/advisor for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galderma, Incyte Corporation, Janssen-Cilag, Kyowa Kirin, LEO Pharma, New Bridge, Novartis, Pfizer, Regeneron, Samsung, Sanofi, Target-RWE, and UCB and has received grants from AbbVie, LEO Pharma, and Novartis. LM has served as an investigator, consultant, and/or advisor for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galderma, Incyte Corporation, Janssen-Cilag, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, and Sanofi. AWA has served as a research investigator and/or scientific advisor to AbbVie, Bristol Myers Squibb, Dermavant, Dermira, Incyte Corporation, Janssen, LEO Pharma, Lilly, Modmed, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. AB has served as a speaker (received honoraria) for Eli Lilly and Company and UCB; served as a scientific advisor (received honoraria) for AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Apogee, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Celldex, CTI BioPharma, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte Corporation, InnoventBio, Janssen, Landos, LEO Pharma, Lipidio, Microbion, Merck, Monte Rosa Therapeutics, Nektar, Novartis, Overtone Therapeutics, Paragon, Pfizer, Q32 Bio, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB Pharma, Union, Ventyx, Vibliome, and Xencor; acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, DermBiont, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte Corporation, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, Takeda, UCB Pharma, and Ventyx; and owns stock in Lipidio and Oruka. KAP has received honoraria and/or grants from AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, DiCE Pharmaceuticals, DiCE Therapeutics, Eli Lilly and Company, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte Corporation, Janssen, Kymab, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB Pharma, and Zai Lab. JCS has served as an advisor for AbbVie, LEO Pharma, Novartis, Pierre Fabre, Trevi, and UCB; has received speaker honoraria from AbbVie, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, and Sanofi Genzyme; and has received clinical trial funding from AbbVie, Almirall, Amgen, Galapagos, Holm, Incyte Corporation, InflaRX, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Trevi, and UCB. MB has served as an investigator for Incyte Corporation, Regeneron, and Sanofi and has served as an advisor for AbbVie, Amgen, Dermavant, Eli Lilly, Incyte Corporation, Janssen, LEO Pharma, Pfizer, Regeneron, and Sanofi Genzyme. SGK has served as an advisory board member or consultant for AbbVie, Celldex Therapeutics, Galderma, Incyte Corporation, Johnson & Johnson, Kiniksa Pharmaceuticals, Novartis, Pfizer, Regeneron, and Sanofi and has served as an investigator for Galderma, Pfizer, and Sanofi. HK, DS, and HR are employees and shareholders of Incyte Corporation. LK has served as an investigator, consultant, or speaker for AbbVie, Amgen, AnaptysBio, Arcutis, Dermavant, Eli Lilly, Glenmark, Incyte Corporation, Kamedis, LEO Pharma, L’Oreal, Menlo Therapeutics, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and Taro. Ethics Approval These studies were conducted in accordance with Good Clinical Practice guidelines, provisions of the Declaration of Helsinki, and applicable regulations. Both study protocols were approved by all relevant institutional review boards or ethics committees. Consent to Participate Written informed consent or assent was provided by all patients before enrollment. Consent to Publish Not applicable. Availability of Data and Materials Incyte Corporation (Wilmington, DE, USA) is committed to data sharing that advances science and medicine while protecting patient privacy. Qualified external scientific researchers may request anonymized datasets owned by Incyte for the purpose of conducting legitimate scientific research. Researchers may request anonymized datasets from any interventional study (except phase I studies) for which the product and indication have been approved on or after 1 January 2020 in at least one major market (e.g., US, EU, JPN). Data will be available for request after the primary publication or 2 years after the study has ended. Information on Incyte’s clinical trial data sharing policy and instructions for submitting clinical trial data requests are available at: https://www.incyte.com/Portals/0/Assets/Compliance%20and%20Transparency/clinical-trial-data-sharing.pdf?ver=2020-05-21-132838-960. Code Availability Not applicable. Authors’ Contributions ELS, MA, DT, LM, AWA, AB, KAP, JCS, SGK, and LK contributed to data collection and interpretation. MB, HK, and DS contributed to data interpretation. HR contributed to data analysis and reporting. All authors contributed to draft development and critical appraisal of the manuscript and approved the final version for submission., (© 2024. The Author(s).)

Atopic dermatitis (AD) is a common chronic pruritic inflammatory skin disease that affects all ages and is recognized as a global health problem. Pathophysiology is complex with skin barrier abnormalities, immune dysregulation, and microbial dysbiosis all implicated. Markers of immune and inflammatory activation in the circulation provide a rationale for systemic therapy. Type 2 immune polarization is central, though other cytokine pathways including Th22 and Th17/IL-23 have been described, suggesting additional therapeutic targets in a subset of patients. Dupilumab and tralokinumab are monoclonal antibodies currently approved for moderate-to-severe AD with lebrikizumab and nemolizumab in late stages of development., Competing Interests: Disclosure M. Nevid has no conflicts to disclose. M. Boguniewicz has been involved in clinical research for Regeneron and Sanofi-Genzyme and served as a consultant for Amgen, Eli Lilly, LEO Pharma, Regeneron, and Sanofi-Genzyme., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Atopic dermatitis is a common chronic inflammatory skin disorder, with a complex pathogenesis. It is characterized by eczematous skin lesions, pruritus, and recurrent skin infections and has a negative impact on patients' and caregivers' quality of life. The American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Atopic Dermatitis Guideline Panel recently released updated AD guidelines. This guideline focuses on addressing clinical questions using trustworthy guideline development standards, including mitigating the potential influence of financial and nonfinancial conflicts of interest, and Grading of Recommendations Assessment, Development, and Evaluation methodology. A multidisciplinary panel used systematic reviews and meta-analyses to inform specific recommendations addressing optimal use of topical treatments, dilute bleach bath, dietary avoidance/elimination, allergen immunotherapy, and systemic treatments. The comprehensive recommendations, emphasizing the third principle of evidence-based medicine-that evidence alone is never enough, and that patient values and preferences must be carefully considered when determining optimal treatments for patients and populations-provide a framework to support clinicians in selecting an optimal treatment plan for each patient. This review provides an overview of the guideline and discusses how those recommendations relate to current practice., (Copyright © 2024. Published by Elsevier Inc.)

Atopic dermatitis (AD) is a chronic, type-2 mediated, inflammatory skin disease characterized by intense pruritus, disruption of skin barrier function, and immune dysregulation. Management strategies for AD are routinely determined based on disease severity. First-line treatment begins with basic skin care and topical anti-inflammatory medication, which is typically sufficient for the management of mild-to-moderate disease. For those patients with moderate-to-severe disease, systemic therapy is often required. This can involve off-label treatment with conventional immunosuppressant medications. However, this approach is limited by a lack of robust clinical trial data and safety concerns that necessitate close monitoring. The emergence of novel targeted biologics and small molecules to treat AD presents an opportunity to optimize AD management and patient outcomes by offering greater efficacy than traditional immunosuppressants and a favorable safety profile. As the treatment landscape shifts, clinicians can benefit from a standardized process of patient assessment and treatment, along with resources to help maintain contemporary knowledge of available therapeutic options. This US-based, expert-led consensus used a modified Delphi process to develop core recommendations for the use of systemic medications for the management of pediatric patients <18 years of age with moderate-to-severe AD., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Atopic dermatitis (AD) is an inflammatory skin condition characterized by widely variable cutaneous Staphylococcus aureus abundance that contributes to disease severity and rapidly responds to type 2 immune blockade (ie, dupilumab). The molecular mechanisms regulating S aureus levels between AD subjects remain poorly understood., Objective: We investigated host genes that may be predictive of S aureus abundance and correspond with AD severity., Methods: We studied data derived from the National Institutes of Health/National Institute of Allergy and Infectious Diseases-funded (NCT03389893 [ADRN-09]) randomized, double-blind, placebo-controlled multicenter study of dupilumab in adults (n = 71 subjects) with moderate-to-severe AD. Bulk RNA sequencing of skin biopsy samples (n = 57 lesional, 55 nonlesional) was compared to epidermal S aureus abundance, lipidomic, and AD clinical measures., Results: S aureus abundance and ceramide synthase 1 (CERS1) expression positively correlated at baseline across both nonlesional (r = 0.29, P = .030) and lesional (r = 0.41, P = .0015) skin. Lesional CERS1 expression also positively correlated with AD severity (ie, SCORAD r = 0.44, P = .0006) and skin barrier dysfunction (transepidermal water loss area under the curve r = 0.31, P = .025) at baseline. CERS1 expression (forms C 18:0 sphingolipids) was negatively associated with elongation of very long-chain fatty acids (ELOVL6; C 16:0 →C 18:0 ) expression and corresponded with a shorter chain length sphingolipid composition. Dupilumab rapidly reduced CERS1 expression (day 7) and ablated the relationship with S aureus abundance and ELOVL6 expression by day 21., Conclusion: CERS1 is a unique molecular biomarker of S aureus abundance and AD severity that may contribute to dysfunctional skin barrier and shorter-chain sphingolipid composition through fatty acid sequestration as a maladaptive compensatory response to reduced ELOVL6., Competing Interests: Disclosure statement Supported by grants from the National Institutes of Health (NIH), including T32GM007356 (to H.M.K.), F30AG076326 (H.M.K.), U19AI117673 (Atopic Dermatitis Research Network [ADRN] investigators), UM1AI151958 (ADRN investigators), UM2AI117870 (Rho Inc), and UM1TR004399 (University of Colorado investigators). This article’s contents are the authors’ sole responsibility and do not necessarily represent official NIH views. Disclosure of potential conflict of interest: L. A. Beck has been consultant for Allakos, Arcutis Biotherapeutics, Arena Pharmaceuticals, Dermavent, DermTech, Evelo Biosciences, Galderma, Incyte, Janssen, LEO Pharma, Merck, Nektar Therapeutics, Numab Therapeutics, Pfizer, Rapt Therapeutics, Regeneron, Ribon Therapeutics, Sanofi/Genzyme, Sanofi-Aventis, Stealth BioTherapeutics, Trevi Therapeutics, Union Therapeutics, and Xencor; and investigator for AbbVie, AstraZeneca, DermTech, Kiniksa, Pfizer, Regeneron, Ribon Therapeutics, and Sanofi. M. Boguniewicz has been investigator and advisory board member for Regeneron and Sanofi. Z. C. Chiesa Fuxench has received research grants from Lilly, Brexogen, LEO Pharma, Regeneron, Sanofi, Tioga, and Vanda for work related to atopic dermatitis, and from Menlo Therapeutics and Galderma for work related to prurigo nodularis; has served as consultant for the Asthma and Allergy Foundation of America, National Eczema Association, AbbVie, Incyte, and Pfizer; and received honoraria for continuing medical education work in atopic dermatitis sponsored by education grants from Regeneron/Sanofi and Pfizer and from Beirsdorf for work related to skin cancer and sun protection. A. De Benedetto has been a consultant for AbbVie, Incyte, and Sanofi-Advent; and has received grant or clinical trial support paid to institution from Incyte and Pfizer. D. Y. M. Leung reports grants to his institution from National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Genentech, and Sanofi; and personal consulting fees from Sanofi, Jasper Therapeutics, and Leo Pharma. P. Y. Ong has been on advisory boards for Dermavant, Amgen, Johnson & Johnson, and AbbVie; and has received research funding from Incyte, Leo, Regeneron, and Sanofi. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians., Objective: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab., Methods: A systematic review of the literature was performed, and an expert Delphi Panel was assembled., Results: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective., Conclusion: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity., Competing Interests: Disclosures J.A.L. served as consultant for ARS, Aquestive, Bryn, ALK, and Novartis and Co-Chair Joint Task Force for Practice Parameters; received research money to institution from DBV and adjudication for Abvie and Siolta. T.E.D. the project described was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH), under Award Number 2UL1TR001425 - 05A1; the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. E.M.A. is and employee of Public Health Agency of Canada, but the views in any paper are her own and not those of Public Health Agency of Canada. Board member of the Canadian Society of Allergy and Clinical Immunology and Head of Allergy Section, Canadian Pediatric Society. A.A. received institutional funding (Novartis) and consultation/speaker fees (ALK, EPG Health, MJH, Adelphi, Genentech, FARE, and Medscape) and served as advisory board member (Ready, Set, Food; Novartis; and Genentech). K.G.B. received grants from NIH (R01AI150295), AHRQ (R01HS029319), and Thermo Fisher Scientific and royalties from UpToDate and is consulting for Denali Therapeutics. M.B. serves as investigator and advisory board member for Regeneron and Sanofi. N.M.C. serves as clinical investigator; received research support from AstraZeneca, Genentech, and Kenota Health; serves as advisor, consultant, and/or speaker for Amgen, ARS Pharma, AstraZeneca, Blueprint Medicines, Bryn Pharma LLC, Freed AI, Genentech, GSK, Hikma, Incyte, Novartis, Regeneron, and Sanofi. D.B.K.G. is a consultant for Novartis, Aquestive, CellDex, and Kokua; received clinical trials support from Genentech, Novartis, Pfizer, GSK, Merck, Regeneron, Allergy Therapeutics, Eli Lilly, and AstraZeneca and royalties from UpToDate. N.L.H. is a speaker for Adma Bio and Takeda; speaker and advisor for Pharming, Horizon/Amgen, Horizon; advisory board member and speaker for Pharmaceuticals/Amgen. M.G.L. received research money to institution from Regeneron. S.S.M. is speaker for Genentech, Regeneron/Sanofi, GSK, and AstraZeneca and received grant from Takeda. J.J.O. consultant/advisor: GSK, Aquestive, Amgen, and ARS; adjudication/DSMB: AZ, Novartis, GSK, Sanofi, and AbbVie; reviewer/editor and executive editor: Annals of Allergy, Asthma & Immunology; reviewer: UpToDate; executive editor: Medscape; research/grants: NIH. A.R. speakers bureau member for Sanofi/Regeneron, GSK, and AstraZeneca. N.L.R. received funding from the Jeffrey Modell Foundation (58293-I), the NIH (R21AI164100), and Takeda Pharmaceuticals; is consultant for Takeda, Pharming Healthcare, and CSL Behring; received royalties from Wolters Kluwer and UpToDate. L.S. is clinical investigator for Regeneron and DBV Technologies and advisor for Sanofi and Leo pharmaceuticals. M.S.S. is member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma, and Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); has participated in research that has received funding from DBV. J.M.S. received grant support from and is consultant for Regeneron/Sanofi. C.A.S. recipient of a AAAAI Foundation Faculty Development Award. The views expressed in this work are the responsibility of the authors and do not necessarily represent the official views of the AAAAI. D.R.S. is consultant to ARS. J.W. received research support from NIAID, Aimmune, DBV Technologies, and Siolta and consultancy fees from ALK Abello, DBV Technologies, and Novartis. M.J.G. is consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Sanofi/Regeneron, Nutricia, Novartis, Acquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, Bryn, Genentech, and Prota; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma, and Immunology; is member of the Joint Taskforce on Allergy Practice Parameters; received honorarium for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, Kaplan, Food Allergy Research and Education, and multiple state/local allergy societies. The remaining authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Patients with atopic dermatitis (AD) often have elevated type 2 inflammatory serum biomarkers., Objective: The aim was to report changes in thymus and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17), total IgE, lactate dehydrogenase (LDH), and eosinophils in pediatric patients treated with dupilumab or placebo., Methods: Biomarker data were analyzed from 3 randomized, double-blind, placebo-controlled, phase 3 studies of patients with moderate-to-severe AD. Patients ages 6 months to 5 years were randomly assigned to weight-dependent dupilumab 200/300 mg every 4 weeks (q4w) or placebo; ages 6 to 11 years, to dupilumab 100/200 mg every 2 weeks (q2w), dupilumab 300 mg q4w, or placebo; ages 12 to 17 years, to dupilumab 200/300 mg q2w, dupilumab 300 mg q4w, or placebo. In the youngest 2 groups, topical corticosteroids were also applied. Median percent changes from baseline to week 16 were reported using last observation carried forward analysis, censoring after rescue treatment., Results: Pediatric patients who received dupilumab versus placebo achieved significantly greater median percent reductions at week 16 in TARC/CCL17 (-83.3% to -72.4% vs -14.9% to -1.8%), total IgE (-71.2% to -58.4% vs -21.0% to +28.1%), and LDH (-26.2% to -9.8% vs -1.5% to +1.5%). All comparisons were significantly different (P < .0001) between each dupilumab dosing group and respective placebo groups. In contrast, absolute changes in eosinophils were small in all groups., Conclusions: Dupilumab treatment for pediatric patients with moderate-to-severe AD significantly reduced levels of TARC/CCL17, total IgE, and LDH to levels comparable with those of healthy controls, reflecting a reduction in systemic type 2 and general inflammation., Competing Interests: Disclosure statement This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Disclosure of potential conflict of interest: L. A. Beck is a consultant for AbbVie, Allakos, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharma, Astria Therapeutics, Celldex, Dermavent, DermTech, Escient Pharma, Eli Lilly and Company, Evelo Biosciences, Galderma, Incyte, Janssen, LEO Pharma, Merck, Nektar Therapeutics, Numab Therapeutics, Pfizer, Proteologix, RAPT Therapeutics, Regeneron Pharmaceuticals Inc, Ribon Therapeutics, Sanofi/Genzyme, Sanofi-Aventis, Sitryx Therapeutics, Stealth BioTherapeutics, Trevi Therapeutics, Union Therapeutics, Xencor, and Yuhan and an investigator for AbbVie, AstraZeneca, DermTech, Kiniksa Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals Inc, Ribon Therapeutics, and Sanofi. A. Muraro is a member of advisory boards and speaker for Aimmune Therapeutics, DVB Technologies, Novartis, Regeneron Pharmaceuticals Inc, Sanofi, and Viatris. M. Boguniewicz is a recipient of research grants and member of advisory boards for Incyte, Regeneron Pharmaceuticals Inc, and Sanofi and a member of advisory boards for AbbVie, Amgen, Dermavant, Eli Lilly and Company, Janssen, LEO Pharma, and Pfizer. Z. Chen and J. Zahn are employees and shareholders of Regeneron Pharmaceuticals Inc. A. Rodríguez Marco is an employee of Sanofi and may hold stock and/or stock options in the company., (Copyright © 2024. Published by Elsevier Inc.)

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.)

Background: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects., Objective: We sought to systematically synthesize the benefits and harms of AD prescription topical treatments., Methods: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s)., Results: The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus., Conclusions: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective., (Copyright © 2023. Published by Elsevier Inc.)

Background: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes., Objective: We sought to systematically synthesize the benefits and harms of AD systemic treatments., Methods: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna)., Results: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain., Conclusions: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is a heterogeneous, chronic, relapsing, inflammatory skin disease associated with considerable physical, psychological, and economic burden. The pathology of AD includes complex interactions involving abnormalities in immune and skin barrier genes, skin barrier disruption, immune dysregulation, microbiome disturbance, and other environmental factors. Many of the cytokines involved in AD pathology, including IL-4, IL-13, IL-22, IL-31, thymic stromal lymphopoietin, and IFN-γ, signal through the Janus kinase (JAK)-signal transducer and activation of transcription (STAT) pathway. The JAK family includes JAK1, JAK2, JAK3, and tyrosine kinase 2; the STAT family includes STAT1, STAT2, STAT3, STAT4, STAT5A/B, and STAT6. Activation of the JAK-STAT pathway has been implicated in the pathology of several immune-mediated inflammatory diseases, including AD. However, the exact mechanisms of JAK-STAT involvement in AD have not been fully characterized. This review aims to discuss current knowledge about the role of the JAK-STAT signaling pathway and, specifically, the role of JAK1 in the pathology and symptomology of AD., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities, and Staphylococcus aureus skin colonization and infections. S aureus is thought to play a role in AD severity., Objectives: This study characterized the changes in the host-microbial interface in subjects with AD following type 2 blockade with dupilumab., Methods: Participants (n = 71) with moderate-severe AD were enrolled in a randomized (dupilumab vs placebo; 2:1), double-blind study at Atopic Dermatitis Research Network centers. Bioassays were performed at multiple time points: S aureus and virulence factor quantification, 16s ribosomal RNA microbiome, serum biomarkers, skin transcriptomic analyses, and peripheral blood T-cell phenotyping., Results: At baseline, 100% of participants were S aureus colonized on the skin surface. Dupilumab treatment resulted in significant reductions in S aureus after only 3 days (compared to placebo), which was 11 days before clinical improvement. Participants with the greatest S aureus reductions had the best clinical outcomes, and these reductions correlated with reductions in serum CCL17 and disease severity. Reductions (10-fold) in S aureus cytotoxins (day 7), perturbations in T H 17-cell subsets (day 14), and increased expression of genes relevant for IL-17, neutrophil, and complement pathways (day 7) were also observed., Conclusions: Blockade of IL-4 and IL-13 signaling, very rapidly (day 3) reduces S aureus abundance in subjects with AD, and this reduction correlates with reductions in the type 2 biomarker, CCL17, and measures of AD severity (excluding itch). Immunoprofiling and/or transcriptomics suggest a role for T H 17 cells, neutrophils, and complement activation as potential mechanisms to explain these findings., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is a chronic, inflammatory, intensely pruritic skin disorder associated with significant patient burden. Interleukin (IL)-13 is a cytokine that acts as a driver of immune dysregulation, skin-barrier dysfunction, and microbiome dysbiosis that characterizes AD, and is consistently overexpressed in AD skin. Tralokinumab is a fully human immunoglobulin (Ig) G4 monoclonal antibody that binds specifically to IL-13 with high affinity, thereby inhibiting subsequent downstream IL-13 signaling. Three pivotal phase 3 clinical trials demonstrated that tralokinumab 300 mg every other week, as monotherapy or in combination with topical corticosteroids as needed, provides significant improvements in signs and symptoms of moderate-to-severe AD, as measured by Investigator's Global Assessment 0/1 (clear/almost clear) and Eczema Area and Severity Index-75 at Week 16. Improvements were observed soon after tralokinumab initiation and were maintained over 52 weeks of therapy. Tralokinumab significantly improved patient-reported outcomes such as itch and sleep, and demonstrated a safety profile comparable with placebo; conjunctivitis during tralokinumab therapy was generally mild. Similar results were observed in a phase 3 adolescent trial. The role of IL-13 in the pathophysiology of AD justifies a targeted approach and a wealth of clinical data supports tralokinumab as a new therapeutic option for people with moderate-to-severe AD., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype., Objective: This study aimed to identify historical and clinical features and biomarkers associated with AD severity., Methods: A US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity., Results: Participants with AD (N = 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001)., Conclusions: In a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Atopic dermatitis (AD) skin lesions are associated with oozing, bleeding, and erythema. This suggests that AD is associated with vascular changes. Dupilumab is an antibody to the alpha subunit of IL-4 receptor that demonstrates strong efficacy in the treatment of AD. IL-4 is known to reduce the permeability barrier function of vascular endothelium., Objective: To examine the effects of dupilumab on vascular barrier function in AD skin., Methods: Using proteomic analysis, we evaluated the plasma protein composition in skin tapes of lesional and nonlesional skin of adults and adolescents with moderate to severe AD over the course of a 16-week treatment with dupilumab and compared those with matched healthy subjects., Results: At baseline, 115 plasma proteins were detected in AD skin and globally increased (1.5-fold or greater) compared with healthy skin. Functionally, these proteins included immunoglobulins, proteins involved in the coagulation process, enzymes, protease inhibitors, transport proteins, acute-phase proteins, complement proteins, and other pleiotropic proteins. Noteworthy, fibrinogens, fibronectin, and heme-binding proteins haptoglobin and hemopexin were among the top proteins originating from plasma and were increased in AD lesional versus healthy skin at baseline (P < .0001). Dupilumab treatment resulted in significantly reduced levels of plasma proteins in AD skin (P < .0001), with most dropping to levels seen in healthy skin or no longer detectable at week 16., Conclusions: Inhibition of IL-4/IL-13 action by dupilumab significantly reduces the efflux of plasma proteins into AD skin. Several of these proteins, such as fibrinogens and fibronectin, are known to enhance Staphylococcus aureus colonization and are associated with AD skin severity., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Importance: Patient values and preferences can inform atopic dermatitis (AD) care. Systematic summaries of evidence addressing patient values and preferences have not previously been available., Objective: To inform American Academy of Allergy, Asthma & Immunology (AAAAI)/American College of Allergy, Asthma and Immunology (ACAAI) Joint Task Force on Practice Parameters AD guideline development, patient and caregiver values and preferences in the management of AD were systematically synthesized., Evidence Review: Paired reviewers independently screened MEDLINE, Embase, PsycINFO, and CINAHL databases from inception until March 20, 2022, for studies of patients with AD or their caregivers, eliciting values and preferences about treatment, rated risk of bias, and extracted data. Thematic and inductive content analysis to qualitatively synthesize the findings was used. Patients, caregivers, and clinical experts provided triangulation. The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research) informed rating of the quality of evidence., Findings: A total of 7780 studies were identified, of which 62 proved eligible (n = 19 442; median age across studies [range], 15 years [3-44]; 59% female participants). High certainty evidence showed that patients and caregivers preferred to start with nonmedical treatments and to step up therapy with increasing AD severity. Moderate certainty evidence showed that adverse effects from treatment were a substantial concern. Low certainty evidence showed that patients and caregivers preferred odorless treatments that are not visible and have a minimal effect on daily life. Patients valued treatments capable of relieving itching and burning skin and preferred to apply topical corticosteroids sparingly. Patients valued a strong patient-clinician relationship. Some studies presented varied perspectives and 18 were at high risk for industry sponsorship bias., Conclusions and Relevance: In the first systematic review to address patient values and preferences in management of AD to our knowledge, 6 key themes that may inform optimal clinical care, practice guidelines, and future research have been identified.

Background: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear., Objective: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD., Methods: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence., Results: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings., Conclusions: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Adults with atopic dermatitis (AD) commonly report adult-onset disease. AD is associated with different genetics, lesion morphology and distribution, and symptoms by age of onset. Yet little is known about possible differences in treatment efficacy between adults with adult-onset or childhood-onset AD., Methods: We evaluated the efficacy of dupilumab by age of AD onset in adults with moderate-to-severe AD, using pooled data from the LIBERTY AD SOLO 1 and 2 studies (NCT02277743, NCT02277769). Results were stratified based on self-reported age of AD onset, divided into four age subgroups: 0-4, 5-9, 10-19, and over 20 years., Results: This analysis included 460 patients treated with placebo and 457 treated with dupilumab 300 mg every 2 weeks (q2w), with a mean patient age of 38 years. Most patients (53.2%) reported AD onset at 0-4 years, with 14% at 5-9 years, 13.4% at 10-19 years, and 18.5% at 20 years or older. Dupilumab significantly improved AD signs and symptoms over 16 weeks compared with placebo, regardless of age of onset. Dupilumab treatment resulted in a significantly greater proportion of patients achieving Eczema Area and Severity Index (EASI)-50, EASI-75, and EASI-90 (50%, 75%, and 90% improvement from baseline EASI, respectively), and clear or almost clear skin (Investigator's Global Assessment score 0 or 1) across all age-of-onset subgroups compared with placebo. In addition, EASI improvements were significant across all anatomical regions in all subgroups. Weekly average peak pruritus Numerical Rating Scale and Dermatology Life Quality Index also improved consistently and significantly with dupilumab versus placebo, regardless of age of onset., Conclusion: Despite possible differences in presentation and progression of AD linked to age of onset, dupilumab showed similar significant and sustained improvements in AD signs, symptoms, and quality of life in adults compared with placebo, over 16 weeks of treatment., Trial Registration: LIBERTY AD SOLO 1: NCT02277743; LIBERTY AD SOLO 2: NCT02277769. Infographic available for this article., (© 2022. The Author(s).)

Background: Emerging treatments for moderate-to-severe atopic dermatitis (AD) may provide greater and faster improvement in AD signs and symptoms than current therapies., Objective: To examine JADE COMPARE (NCT03720470) data using stringent efficacy end points., Methods: Adults with moderate-to-severe AD were randomly assigned 2:2:2:1 to receive oral abrocitinib 200 or 100 mg once daily, subcutaneous dupilumab 300 mg every 2 weeks (600-mg loading dose), or placebo, with medicated topical therapy for 16 weeks. Stringent response thresholds were applied for Eczema Area and Severity Index (EASI), Investigator's Global Assessment, Dermatology Life Quality Index, Peak Pruritus Numerical Rating Scale, and Night Time Itch Scale severity., Results: At week 16, 48.9%, 38.0%, and 38.8% of the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, achieved greater than or equal to 90% improvement from baseline in EASI versus 11.3% placebo; 14.9%, 12.6%, and 6.5% achieved Investigator's Global Assessment 0 (clear) versus 4.8% placebo; 29.7%, 21.6%, and 24.0% achieved Dermatology Life Quality Index 0/1 (no/minimal impact on quality of life) versus 10.6% placebo; and 57.1%, 44.5%, and 46.1% achieved Night Time Itch Scale severity 0/1 (no/minimal night-time itch) versus 31.9% placebo. Kaplan-Meier median time to greater than or equal to 90% improvement from baseline in EASI was 59, 113, and 114 days in the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, and was not evaluable for placebo; median time to Peak Pruritus Numerical Rating Scale 0/1 (no/very minimal itch) was 86 and 116 days for abrocitinib 200-mg and dupilumab groups, respectively, and was not evaluable for abrocitinib 100-mg and placebo groups., Conclusions: A greater proportion of patients treated with abrocitinib than placebo had almost complete control of AD signs and symptoms., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

To address the need for long-term efficacy and patient-reported outcomes (PROs) data for patients with atopic dermatitis (AD) treated with baricitinib 2 mg, a study was conducted to evaluate the efficacy of baricitinib 2 mg in adult patients with moderate-to-severe AD. Data presented here provided efficacy and outcomes data for patients treated for 52 weeks. Patients who participated in the originating study, BREEZE-AD5 (NCT03435081), and met additional eligibility criteria could enroll in the multicenter, open-label, Phase 3, long-term extension study BREEZE-AD6 (NCT03559270). Patients received baricitinib 2 mg for the duration of BREEZE-AD6. In BREEZE-AD6, the proportion of patients who achieved a 75% improvement in the Eczema Area and Severity Index (EASI75) and validated Investigator Global Assessment for AD (vIGA-AD™) of 0 (clear) or 1 (almost clear) were assessed through 52 weeks, in addition to several PROs. At week 52, the proportion of patients treated with baricitinib 2 mg daily achieving EASI75 was 48.6% (70/144), and 31.3% (45/144) of patients achieved a vIGA-AD score of 0 or 1 (clear or almost clear). Improvements in PROs such as SCORing Atopic Dermatitis (SCORAD, itch and sleep) scores, Dermatology Life Quality Index (DLQI) total score, and DLQI ≤5 response were observed, and these responses were sustained through 52 weeks. Long-term efficacy of baricitinib in patients with AD was demonstrated by both clinician and patient-reported outcome measures., (© 2022 Wiley Periodicals LLC.)

Background: The relationship between atopic dermatitis (AD) severity, sleep disturbance (SD), and health-related outcomes is not fully elucidated., Objective: The aim of the study was to determine the prevalence of SD in adult AD and its relationship with AD severity and health outcomes among the US population., Methods: A cross-sectional, US population-based survey study of 2893 adults was performed., Results: Among adults meeting the UK Diagnostic Criteria for AD, 255 (40.7%) reported 1 or more, 67 (11.1%) reported 3 to 4, and 57 (9.5%) reported 5 to 7 nights of SD in the past week; 475 (79.7%) reported at least some trouble sleeping in the past 3 days. Moderate and severe Patient-Oriented Scoring AD, Patient-Oriented Eczema Measure, and Numeric Rating Scale-itch and Numeric Rating Scale-skin pain scores were associated with more severe SD compared with those without AD. More frequent and severe SDs were associated with higher Dermatology Life Quality Index, lower 12-item Short-Form Health Survey, and higher Hospital Anxiety and Depression Scale (HADS) scores. Significant mediation by SD severity was observed between Patient-Oriented Eczema Measure and Numeric Rating Scale-itch with Dermatology Life Quality Index, 12-item Short-Form Health Survey physical and mental component scores, HADS-anxiety and HADS-depression scores, diagnosed anxiety, and heart disease., Conclusions: Atopic dermatitis and AD severity are associated with SDs. Sleep disturbances considerably impact quality of life and other health outcomes in adults with AD., (Copyright © 2021 American Contact Dermatitis Society. All Rights Reserved.)

Background: Atopic dermatitis (AD) is characterized by abnormal skin lipids that are largely driven by hyperactivated type 2 immune responses. The antibody to the α-subunit of interleukin (IL)-4 receptor, dupilumab, was recently approved to treat AD and demonstrated strong efficacy. However, the role of dupilumab therapy in the regulation of skin barrier structure and function has not been fully explored., Methods: We have evaluated the content of lipids and transepidermal water loss (TEWL) in lesional and non-lesional skin of adults and adolescents with moderate-to-severe AD over the course of 16-week treatment with dupilumab and compared those values with that of matched healthy volunteers., Results: Dupilumab treatment provided a significant decrease in TEWL in AD lesions, lowering it almost to the levels seen in the skin of healthy subjects. Blocking IL-4/IL-13 signaling with dupilumab normalized lipid composition (decreased levels of ceramides with non-hydroxy fatty acids and C18-sphingosine and increased the level of esterified omega-hydroxy fatty acid-containing ceramides) and increased ceramide chain length in lesional as well as non-lesional stratum corneum of AD patients. Partial changes for these parameters were already observed after 2 weeks, with a full response achieved after 8 weeks of dupilumab treatment., Conclusions: Inhibition of IL-4/IL-13 signaling by dupilumab allows restoration of skin lipid composition and barrier function in patients with moderate-to-severe AD., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The influence of diet on atopic dermatitis (AD) is complex, and the use of dietary elimination as a treatment has conflicting views., Objective: To systematically review the benefits and harms of dietary elimination for the treatment of AD., Methods: We searched MEDLINE, Embase, AMED, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to January 18, 2022, without language restrictions, for randomized controlled trials (RCTs) and observational studies comparing dietary elimination and no dietary elimination for the treatment of AD. We conducted random-effects meta-analyses of eczema outcomes. We used the grading of recommendations, assessment, development, and evaluation approach to assess certainty of evidence (CRD42021237953)., Results: Ten RCT (n = 599; baseline median of study mean age, 1.5 years; median of study mean SCOring Atopic Dermatitis index, 20.7, range, 3.5-37.6) were included in the meta-analysis. Compared with no dietary elimination, low-certainty evidence showed that dietary elimination may slightly improve eczema severity (50% with vs 41% without dietary elimination improved the SCOring Atopic Dermatitis index by a minimally important difference of 8.7 points, risk difference of 9% [95% CI, 0-17]), pruritus (daytime itch score [range, 0-3] mean difference, -0.21 [95% CI, -0.57 to 0.15]), and sleeplessness (sleeplessness score [range, 0-3] mean difference, -0.47 [95% CI, -0.80 to -0.13]). There were no credible subgroup differences based on elimination strategy (empiric vs guided by testing) or food-specific sensitization. Insufficient data addressed harms of elimination diets among included RCTs, although indirect evidence suggests that elimination diets may increase the risk for developing IgE-mediated food allergy., Conclusions: Dietary elimination may lead to a slight, potentially unimportant improvement in eczema severity, pruritus, and sleeplessness in patients with mild to moderate AD. This must be balanced against potential risks for indiscriminate elimination diets including developing IgE-mediated food allergy and withholding more effective treatment options for AD., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Abrocitinib, a once-daily, oral Janus kinase 1 selective inhibitor, was shown to be an effective treatment for moderate-to-severe atopic dermatitis in phase 2 b/3 monotherapy trials., Methods: These analyses included data for Investigator's Global Assessment responder (clear [0] or almost clear [1] with ≥2-grade improvement) and nonresponder patients with moderate-to-severe atopic dermatitis who received abrocitinib (200 mg or 100 mg) or placebo in three abrocitinib monotherapy trials (phase 2 b, NCT02780167; two phase 3, NCT03349060/JADE MONO-1 and NCT03575871/JADE MONO-2). Outcomes measuring skin clearance, itch, and quality of life were evaluated., Results: Both nonresponders ( n  = 548) and responders ( n  = 260) treated with abrocitinib had rapid and clinically meaningful improvement in skin clearance, itch, and quality of life compared with placebo., Conclusion: Patients with moderate-to-severe atopic dermatitis treated with abrocitinib who did not achieve an Investigator's Global Assessment 0/1 response at week 12 still experienced rapid, clinically meaningful improvements across several other validated measures of efficacy and quality of life., Clinicaltrials.gov: NCT02780167, NCT03349060, NCT03575871.

Background: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain., Objective: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD., Methods: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses., Results: There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty., Conclusion: In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials., Trial Registration: PROSPERO Identifier: CRD42021238486., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, is indicated in the European Union and Japan for treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. In the ongoing, placebo-controlled, phase 3 trial BREEZE-AD5, once-daily oral baricitinib 2-mg monotherapy improved disease in moderate-to-severe AD patients who had an inadequate response or intolerance to topical corticosteroids. This post-hoc analysis aimed to identify responders to baricitinib 2 mg, using a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement, in BREEZE-AD5., Methods: Classification and regression tree method was used to evaluate baseline predictors for the proportion of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI75) at week 16 among baricitinib 2-mg-treated patients. Two-by-two contingency tables evaluated the association between early response, defined as ≥ 50% improvement in BSA or ≥ 3-point improvement in Itch Numeric Rating Scale from baseline at weeks 4 or 8, and response at week 16 for the proportion of patients achieving EASI75, validated Investigator Global Assessment for AD (vIGA-AD) score of 0 or 1, or ≥ 4-point improvement in Itch (Itch ≥ 4), respectively. Missing data were imputed as non-responder., Results: At week 16, EASI75 and vIGA-AD (0,1) were achieved by 37.5% and 31.7% of baricitinib 2-mg-treated patients with baseline BSA 10-50% compared with 9.5% and 4.8% with BSA > 50%. Early response in skin inflammation or itch at week 4 was associated with corresponding EASI75, vIGA-AD (0,1), and Itch ≥ 4 of 55.4%, 48.2%, and 39.3% at week 16, while early response at week 8 was associated with 66.7%, 56.1%, and 42.1% of patients achieving these endpoints., Conclusion: Baseline BSA of 10-50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may identify patients most likely to benefit from long-term baricitinib 2-mg therapy., Clinical Trial Registration: NCT03435081., (© 2021. The Author(s).)

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo- controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis.

Background: Laboratory testing is typically required for patients with atopic dermatitis (AD) treated with systemic immunosuppressants. A previous analysis of laboratory outcomes in randomized, double-blinded, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD found no clinically important changes in hematologic, serum chemistry, and urinalysis parameters, supporting the use of dupilumab without routine laboratory monitoring., Objective: The aim was to assess laboratory results in adolescents with moderate-to-severe AD treated with dupilumab in a phase 3, randomized, double-blind, placebo-controlled trial., Methods: Adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD were randomized 1:1:1 to subcutaneous dupilumab 200/300 mg every 2 weeks (q2w) (200 mg for patients < 60 kg at baseline; 300 mg for patients ≥ 60 kg at baseline); dupilumab 300 mg every 4 weeks (q4w); or placebo for 16 weeks. Laboratory evaluations included hematology, serum chemistry, and urinalysis parameters., Results: Of 251 patients enrolled in the study, 250 received treatment and were included in the analysis. 4.7%, 2.4%, and 4.8% of patients receiving placebo, dupilumab 200/300 mg q2w, and dupilumab 300 mg q4w, respectively, had laboratory abnormalities reported as treatment-emergent adverse events, none of which prompted discontinuation of study treatment or study withdrawal. Mean eosinophil counts were elevated at baseline in all treatment groups. Patients in both dupilumab regimens, but not the placebo group, showed mild transient increases in mean eosinophil counts above baseline that returned to near-baseline values by week 16. Mean levels of lactate dehydrogenase trended towards the upper limit of normal at baseline and decreased with treatment; greater decreases were seen in dupilumab-treated patients than placebo-treated patients. There were no meaningful changes in other laboratory parameters, and none of the laboratory abnormalities were clinically significant., Conclusion: No clinically meaningful changes in laboratory parameters were seen in adolescents, similar to that observed in adults. The findings of this study indicate no routine laboratory monitoring is required in this population prior to or during dupilumab treatment., Trial Registration: ClinicalTrials.gov: NCT03054428. Video abstract: Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized Placebo-Controlled Phase 3 Clinical Trial (MP4 175137 KB).

Background: Dupilumab has demonstrated efficacy with acceptable safety in clinical trials in patients with moderate to severe atopic dermatitis (AD)., Objective: To assess dupilumab's impact on asthma and sinonasal conditions in adult patients with moderate to severe AD in four randomized, double-blinded, placebo-controlled trials., Methods: In LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02755649), CHRONOS (NCT02260986), and CAFÉ (NCT02755649), patients received placebo, dupilumab 300 mg every 2 weeks (q2w), or dupilumab 300 mg weekly (qw). In CHRONOS and CAFÉ, patients received concomitant topical corticosteroids. This post hoc analysis assessed Asthma Control Questionnaire-5 (ACQ-5) scores in patients with asthma, Sino-Nasal Outcome Test-22 (SNOT-22) scores in patients with sinonasal conditions, and AD signs and symptoms in all patients., Results: Of the 2444 patients, 463 had asthma with baseline ACQ-5 ≥ 0.5 (19%); 1171 had sinonasal conditions (48%); and 311 had both (13%). At week 16, ACQ-5 scores (least squares mean change from baseline [standard error]) improved by 0.27 (0.07), 0.59 (0.08), and 0.56 (0.07) in placebo-, q2w-, and qw-treated patients with asthma, respectively, whereas SNOT-22 scores improved by 5.1 (0.8), 9.9 (0.9), and 10.8 (0.8) in patients with sinonasal conditions (P < .01 for all dupilumab vs placebo). Improvements in ACQ-5 and SNOT-22 were also seen in patients with both conditions. Dupilumab also significantly improved AD signs and symptoms among all subgroups., Conclusions: In this first analysis of patients with comorbid moderate to severe AD, asthma, and/or chronic sinonasal conditions, dupilumab improved all three diseases in a clinically meaningful and statistically significant manner (vs placebo), based on validated outcome measures., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is complicated by an increased risk for skin and systemic infections. Preventive therapy for AD is based on skin barrier improvement and anti-inflammatory treatments, whereas overt skin and systemic infections require antibiotics or antiviral treatments. This review updates the pathophysiology, diagnosis, management, controversy of antibiotic use, and potential treatments of infectious complications of AD., Data Sources: Published literature obtained through PubMed database searches and clinical pictures., Study Selections: Studies relevant to the mechanisms, diagnosis, management, and potential therapy of infectious complications of AD., Results: Skin barrier defects, type 2 inflammation, Staphylococcusaureus colonization, and cutaneous dysbiosis are the major predisposing factors for the increased infections in AD. Although overt infections require antibiotics, the use of antibiotics in AD exacerbation remains controversial., Conclusion: Infectious complications are a comorbidity of AD. Although not common, systemic bacterial infections and eczema herpeticum can be life-threatening. Preventive therapy of infections in AD emphasizes skin barrier improvement and anti-inflammatory therapy. The use of antibiotics in AD exacerbation requires further studies., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that has become a global health problem. The pathophysiology of AD includes both skin barrier and immune abnormalities, with type 2 immune deviation central to several clinical phenotypes and underlying endotypes. Recognition of the persistent nature and systemic aspects of AD provides a rationale for treatment with a biologic. Dupilumab has been approved for patients 6 years of age and older with moderate to severe AD. Monoclonal antibodies are in phase 3 trials and may become part of a precision medicine approach to AD., Competing Interests: Conflict of interest M. Boguniewicz has served as a consultant for Regeneron and Sanofi-Genzyme., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Children with severe atopic dermatitis (AD) have limited treatment options., Objective: We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years with severe AD inadequately controlled with topical therapies., Methods: In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight <30 kg; 200 mg q2w, baseline weight ≥30 kg), or placebo; with concomitant medium-potency TCS., Results: Both the q4w and q2w dupilumab + TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo + TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator's Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children <30 kg and 200 mg q2w in children ≥30 kg. Conjunctivitis and injection-site reactions were more common with dupilumab + TCS than with placebo + TCS., Limitations: Short-term 16-week treatment period; severe AD only., Conclusion: Dupilumab + TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QOL., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator's Global Assessment 0/1 at week 16., Objective: The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life., Methods: R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator's Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children's Dermatology Life Quality Index from baseline., Results: Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5-69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9-53.3]; both p < 0.0001). Results were similar in adolescents with Investigator's Global Assessment > 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5-66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7-48.1]; both p < 0.0001)., Conclusions: Dupilumab provided clinically meaningful improvements in signs, symptoms, and quality of life in adolescents with moderate-to-severe atopic dermatitis among patients with Investigator's Global Assessment > 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures., Trial Registration: ClinicalTrials.gov; NCT03054428. Adolescents with atopic dermatitis: does dupilumab improve their signs, symptoms, and quality of life? (MP4  212916 kb).

Importance: Adolescents with atopic dermatitis (AD) have high disease burden negatively affecting quality of life, with limited treatment options. The efficacy and safety of dupilumab, a monoclonal antibody, approved for treatment in adolescent patients with inadequately controlled AD, remain unknown in this patient population., Objective: To assess the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled AD., Design, Setting, and Participants: A randomized, double-blind, parallel-group, phase 3 clinical trial was conducted at 45 US and Canadian centers between March 21, 2017, and June 5, 2018. A total of 251 adolescents with moderate to severe AD inadequately controlled by topical medications or for whom topical therapy was inadvisable were included., Interventions: Patients were randomized (1:1:1; interactive-response system; stratified by severity and body weight) to 16-week treatment with dupilumab, 200 mg (n = 43; baseline weight <60 kg), or dupilumab, 300 mg (n = 39; baseline weight ≥60 kg), every 2 weeks; dupilumab, 300 mg, every 4 weeks (n = 84); or placebo (n = 85)., Main Outcomes and Measures: Proportion of patients with 75% or more improvement from baseline in Eczema Area and Severity Index (EASI-75) (scores range from 0 to 72, with higher scores indicating greater severity) and Investigator's Global Assessment (IGA) 0 or 1 on a 5-point scale (scores range from 0 to 4, with higher scores indicating greater severity) at week 16., Results: A total of 251 patients were randomized (mean [SD] age, 14.5 [1.7] years; 148 [59.0%] male). Of 250 patients with data available on concurrent allergic conditions, most had comorbid type 2 diseases (asthma, 134 [53.6%]; food allergies, 60.8%; allergic rhinitis, 65.6%). A total of 240 patients (95.6%) completed the study. Dupilumab achieved both coprimary end points at week 16. The proportion of patients with EASI-75 improvement from baseline increased (every 2 weeks, 41.5%; every 4 weeks, 38.1%; placebo, 8.2%) with differences vs placebo of 33.2% (95% CI, 21.1%-45.4%) for every 2 weeks and 29.9% (95% CI, 17.9%-41.8%) for every 4 weeks (P < .001). Efficacy of the every-2-week regimen was generally superior to the every-4-week regimen. Patients in the dupilumab arms had higher percentage values of conjunctivitis (every 2 weeks, 9.8%; every 4 weeks, 10.8%; placebo, 4.7%) and injection-site reactions (every 2 weeks, 8.5%; every 4 weeks, 6.0%; placebo, 3.5%), and lower nonherpetic skin infections (every 2 weeks, 9.8%; every 4 weeks, 9.6%; placebo, 18.8%)., Conclusions and Relevance: In this study, dupilumab significantly improved AD signs, symptoms, and quality of life in adolescents with moderate to severe AD, with an acceptable safety profile. Placebo-corrected efficacy and safety of dupilumab were similar in adolescents and adults., Trial Registration: ClinicalTrials.gov identifier: NCT03054428.

Background: The Atopic Dermatitis Control Tool (ADCT©) is a brief patient self-administered instrument designed and validated to assess atopic dermatitis (AD) control; six AD symptoms and impacts are evaluated over the past week, including overall severity of symptoms, days with intense episodes of itching, intensity of bother, problem with sleep, impact on daily activities, and impact on mood or emotions. This study assessed the reliability, validity, and responsiveness of the ADCT in a longitudinal context, and provided thresholds to identify meaningful within-person change., Methods: Data were from a prospective, longitudinal patient survey study of real-world effectiveness of dupilumab in patients with AD. Eligible patients completed a baseline survey before starting dupilumab and were followed at Months 1, 2, 3, and 6 post-initiation as they became eligible., Results: Psychometric analyses confirmed internal consistency; Cronbach's α coefficients were consistently above the threshold of 0.70 across each follow-up; item-to-total correlations were above the threshold of r ≥ 0.50. High correlations between the ADCT and the Dermatology Life Quality Index (DLQI) and skin pain supported construct validity, while known-group validity was shown on Patient Global Assessment of Disease (PGAD) overall well-being subgroups with worse AD-related overall well-being having higher mean ADCT total scores at all time points. The ability of the ADCT to detect change was confirmed; the threshold for meaningful within-person change was estimated to be 5 points. Finally, test-retest reliability was confirmed in subgroups of patients with stable PGAD responses., Conclusions: Our findings confirm that the ADCT is a valid and reliable tool for assessing AD control.

Background: Atopic dermatitis (AD) is associated with skin pain. However, little is known about the prevalence and associations of pain in AD., Objective: To characterize the frequency, intensity, characteristics, and associations of pain from AD., Methods: A cross-sectional, US population internet survey-based study of 602 adults with AD from the AD in America Study was performed (modified UK Working Party Criteria)., Results: Overall, 365 (61%) reported pain from AD, with 199 (33%) experiencing pain at least once per week and 30 (5%) with pain daily. Among those with AD pain, 22% reported worst pain intensity ≥7. The frequency and intensity of AD pain were associated with Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD), PO-SCORAD itch and sleep, and Patient-Oriented Eczema Measure (P ≤ .004 for all). Among those experiencing AD pain, 179 (48%) reported pain occurring only after frequent scratching, 156 (42%) reported intermittent pain, and 27 (11%) reported constant pain throughout the day. AD pain was most commonly associated with open areas caused by scratching (27%) and fissures in the skin (27%), followed by inflamed red skin (25%), with only a minority reporting pain mostly caused by burning from creams or ointments (10%). Mild AD was associated with more pain from scratching, whereas severe AD was associated with more constant pain and pain from inflamed skin., Conclusions: Pain is a distinct symptom in AD, with heterogeneous frequency, characteristics, intensity, and quality of life impact. Pain was related to scratching, fissures, and/or inflamed red skin, and least from burning from topical medications. Skin pain should be assessed in patients with AD and monitoring treatment response., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Quality-of-life assessments are not standardized in atopic dermatitis (AD). We sought to determine the validity of the Short Form (SF)-12, a generic quality-of-life assessment, in AD and compare its measurement properties with the Dermatology Life Quality Index (DLQI). A cross-sectional, population-based study of 3,495 adults was performed, including 602 adults who met the modified United Kingdom Working Party Criteria for AD. The SF-12 mental component score and the SF-Six Dimension (SF-6D) had a strong correlation with each other and moderate inverse correlations with the Patient-Oriented Eczema Measure, the Patient-Oriented Scoring Atopic Dermatitis, the Patient-Oriented Scoring Atopic Dermatitis-itch, the Patient-Oriented Scoring Atopic Dermatitis-sleep, and the Numerical Rating Scale of pain (Pearson correlations, P < 0.0001 for all). The SF-12 mental component score and the SF-6D showed good discriminant validity as judged by the analysis of variance and receiver operating curves. The SF-12 physical component score had weak correlations with AD severity assessments and poor discriminant validity. The DLQI had better convergent and discriminant validity than the SF-12. The SF-12 and the DLQI showed good internal consistency (Cronbach alpha, 0.89 and 0.94, respectively). Differential item functioning was found for items in the SF-12 and the DLQI. Floor effects were observed for the DLQI but not for the SF-12 mental component score, the SF-12 physical component score, and the SF-6D. Severity thresholds were selected. In conclusion, the SF-12 mental component score and the SF-6D showed good validity in AD but inferior construct validity compared with the DLQI., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the predictors of health care utilization among US adults with atopic dermatitis (AD)., Objective: To determine the proportion and predictors of utilization in outpatient, urgent care, emergency department (ED), and hospital settings in US adults with AD., Methods: A cross-sectional, population-based study of 3495 adults was performed. AD was determined using modified United Kingdom Working Party criteria. AD severity was assessed using the Patient-Oriented Eczema Measure (POEM), the Patient-Oriented Scoring AD (PO-SCORAD), and the Numeric Rating Scale (NRS)-itch. Weighted frequency and prevalence (95% CIs) of utilization were determined., Results: Overall, 10.42% (95% CI, 8.55%-12.28%; weighted frequency, 25,844,871) reported a diagnosis of AD or eczema, 7.39% (95% CI, 5.81%-8.97%; weighted frequency, 18,324,869) met United Kingdom Working Party criteria, and 3.56% (95% CI, 2.40%-4.72%; weighted frequency, 8,830,095) met both. A total of 31.8% (2,711,690) had a severe score for POEM, PO-SCORAD, and/or NRS-itch, with 4.0% (337,586) having severe scores for all 3. Outpatient utilization for AD was low for mild disease (29.3%-34.7%) and increased by severity (moderate: 36.2%-49.8%; severe: 50.6%-86.6%). Timeliness of appointments, expenses, and insurance coverage were also predictors of outpatient utilization. Severe POEM, PO-SCORAD, and/or NRS-itch were associated with being uninsured, not having full prescription coverage, AD prescriptions being denied by insurers, and costs of AD medications being problematic. One in 10 adults with AD had 1 or more urgent care, ED, or hospital visit in the past year. Urgent care or ED visits were significantly more common among blacks and Hispanics, those with lower household income, those with lower education level, and those with AD prescriptions being denied by the insurance company., Conclusions: Adults with AD had low rates of outpatient and high rates of urgent care, ED, and hospital visits. The major predictor of outpatient utilization for AD care was AD severity. Racial/ethnic, socioeconomic, and/or health care disparities reduce outpatient utilization and increase urgent care, ED, and hospital utilization., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The impact of atopic dermatitis (AD) on health-related quality of life and health utility in the US adult population is not well established., Objective: To determine the health utilities and quality-adjusted life-years (QALYs) lost in adults with AD versus without AD in the US population., Methods: A cross-sectional, population-based study of 3495 adults was performed. AD was determined using modified UK diagnostic criteria for AD. AD severity was assessed using self-reported global AD severity, the Patient-Oriented Eczema Measure, the Patient-Oriented Scoring AD, and the Patient-Oriented Scoring AD itch and sleep. Six-dimensional health state short form (SF-6D) health utility scores and total QALY loss were assessed., Results: The mean SF-6D score was lower in adults with AD compared with healthy adults (0.69 [95% CI, 0.68-0.70] versus 0.79 [95% CI, 0.77-0.79]). In particular, those with moderate-to-severe AD (mean, 0.53-0.66) had similar or lower SF-6D scores compared with those with all other self-reported disorders examined, except autoimmune disorders. Adults with AD and atopic comorbidities had significantly lower SF-6D scores compared with those without atopic comorbidities. Among the 7 disorders examined, AD was associated with higher total QALY loss than autoimmune disorders, diabetes, food allergy, and heart disease in both males and females. The largest QALY loss was for moderate AD in females and mild AD in males., Conclusions: Moderate-to-severe AD is associated with significant decrements of health utility in the US population. These data illustrate the heavy societal burden of moderate and severe AD and provide important insight for prioritization of resource allocation and cost-effectiveness research., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Population-based estimates on the prevalence of atopic dermatitis in adults vary widely. The objectives of this study were to determine the prevalence of atopic dermatitis in the population of the United States, the distribution of disease severity, and its impact on health-related quality of life. Among 1,278 participating adults, the prevalence (95% confidence interval) of atopic dermatitis was 7.3% (5.9-8.8). Overall, 60.1% (56.1-64.1) of participants were classified as having mild, 28.9% (25.3-32.7) as having moderate, and 11% as having severe (8.6-13.7) disease. Patients with atopic dermatitis and those with more severe disease had higher scores in the dermatology life quality index (mean [standard deviation] for AD patients = 4.71 [6.44] vs. control individuals = 0.97 [2.12]) (P < 0.001) and the hospital anxiety (mean [standard deviation] for AD patients = 7.03 [4.80] vs. control individuals = 4.73 [4.8]) and depression (mean, [standard deviation] for AD patients = 5.83 [4.54] vs. control individuals = 3.62 [3.61]) scales, indicating a worse impact on quality of life and an increased likelihood of anxiety or depression. Based on our prevalence estimates, 16.5 million adults would have a diagnosis of atopic dermatitis, with 6.6 million meeting criteria for moderate to severe disease. Our study confirms the high prevalence and disease burden of atopic dermatitis in this population., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects around 13% of children and 7% of adults in the US. It can have a significant impact on the quality of life (QoL) of affected individuals due to pruritus and the visibility of lesions on the skin. AD is increasingly recognized as a systemic disease, since dysregulation of the adaptive and innate immune systems plays a key role in the underlying disease pathogenesis, which has important implications for how the condition is treated. Patients with moderate-to-severe disease who have failed to achieve disease control may benefit from systemic immunomodulatory treatments. Recently published expert perspectives outlined recommendations for the diagnosis and treatment of moderate-to-severe AD in adults, reflecting evidence-based, practical recommendations to support allergists and dermatologists in selecting appropriate treatment in the era of biologic therapies. To help clinicians understand how these practical recommendations can be implemented into clinical practice, we describe two real life case studies of adult patients with AD. In these case studies, we demonstrate how AD severity, treatment response, and treatment failure can be assessed, and the role of emerging systemic treatments in the management of moderate-to-severe AD. J Drugs Dermatol. 2019;18(2):122-129.

Patients with severe atopic dermatitis (AD) are reported to represent between 10% and 18% of all patients with AD. However, in this subgroup of patients, quality of life is significantly affected and patients may have a number of atopic and nonatopic comorbidities. Treatment of this severe population has often been reactive with inappropriate use of systemic corticosteroids and unapproved immunosuppressants. Recent insights point to the systemic nature of AD, which has important therapeutic implications. Management of severe AD requires a comprehensive approach that incorporates proper diagnosis, assessment of disease severity, and impact on patient's and caregiver's quality of life, along with education regarding the chronic relapsing nature of the disease as well as treatment options. Biologics such as dupilumab offer a novel, targeted therapeutic approach for this systemic disease., (Copyright © 2019. Published by Elsevier Inc.)

Atopic dermatitis (AD) is a highly prevalent, chronic inflammatory skin disease that affects children and adults. The pathophysiology of AD is complex and involves skin barrier and immune dysfunction. Many immune cytokine pathways are amplified in AD, including T helper (Th) 2, Th22, Th17 and Th1. Current treatment guidelines recommend topical medications as initial therapy; however, until recently, only two drug classes were available: topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). Several limitations are associated with these agents. TCSs can cause a wide range of adverse effects, including skin atrophy, telangiectasia, rosacea and acne. TCIs can cause burning and stinging, and the prescribing information lists a boxed warning for a theoretical risk of malignancy. Novel medications with new mechanisms of action are necessary to provide better long-term control of AD. Phosphodiesterase 4 (PDE4) regulates cyclic adenosine monophosphate in cells and has been shown to be involved in the pathophysiology of AD, making it an attractive therapeutic target. Several PDE4 inhibitors are in clinical development for use in the treatment of AD, including crisaborole, which recently became the first topical PDE4 inhibitor approved for treatment of mild to moderate AD. This review will further describe the pathophysiology of AD, explain the possible role of PDE4 in AD and review PDE4 inhibitors currently approved or being investigated for use in AD., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)