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

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

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

Background: Rademikibart (CBP-201) is a next-generation IL-4 receptor alpha-targeting antibody., Objective: We sought to evaluate rademikibart in adults with moderate to severe atopic dermatitis., Methods: A total of 226 patients were randomized, double-blind, to subcutaneous rademikibart (300 mg every 2 weeks [Q2W], 150 mg Q2W, 300 mg every 4 weeks [Q4W]; plus 600-mg loading dose) or placebo. Randomization began in July 2020. The trial was completed in October 2021., Results: The WW001 phase 2 trial achieved its primary end point: significant percent reduction from baseline in least-squares mean Eczema Area Severity Index (EASI) to week 16 with rademikibart 300 mg Q2W (-63.0%; P = .0007), 150 mg Q2W (-57.6%; P = .0067), 300 mg Q4W (-63.5%; P = .0004) versus placebo (-39.7%). EASI scores decreased significantly with 300 mg Q2W and Q4W at the earliest assessment (week 2), with no evidence of plateauing by week 16. Significant improvements were also observed in secondary end points, including pruritus. Across the primary and secondary end points, efficacy tended to be comparable with 300 mg Q2W and Q4W dosing. Rademikibart and placebo had similar, low incidence of treatment-emergent adverse events (TEAEs) (48% vs 54%), serious TEAEs (1.8% vs 3.6%), TEAEs leading to treatment discontinuation (1.2% vs 1.8%), conjunctivitis of unspecified cause (2.9% vs 0%), herpes (0.6% vs 1.8%), and injection-site reactions (1.8% vs 1.8%). Although no discontinuations were attributed to coronavirus disease 2019, pandemic-related restrictions likely had an impact on trial conduct., Conclusions: Rademikibart was efficacious and well tolerated at Q2W and Q4W intervals. Q4W dosing is a more convenient frequency than approved for current therapies., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. 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 skin disease that can significantly decrease quality of life. AD is commonly associated with comorbidities including ocular surface disease (OSD). Conjunctivitis is the most common OSD associated with AD and can increase in incidence with use of monoclonal antibody biologics that target the type 2 inflammatory pathway. The objective of this review is to raise awareness of comorbid OSD in AD patients that dermatologists may encounter, with a focus on conjunctivitis, and equip dermatologists to address mild ocular concerns. We provide background on the subtypes and pathogenesis of comorbid OSD in AD patients and describe OSD associated with type 2 inflammation-inhibiting AD biologics. We also discuss screening and diagnosis, recommended treatment options for dermatologists, and when to refer to an eye care specialist. This multispecialty approach aims to support the overall health of AD patients and provide optimal patient care., Competing Interests: Conflicts of interest Dr Shi is on the board of directors for the Hidradenitis Suppurativa Foundation (HSF); an advisor for the National Eczema Association; is a stock shareholder of Learn Health; and has served as an advisory board member, investigator, speaker, and/or received research funding from AbbVie, Altus Lab/cQuell, Aristea Therapeutics, Boehringer Ingelheim, Burt's Bees, Dermira, Ely Lilly, Galderma, GPSkin, Incyte, Kiniksa, LEO Pharma, Menlo Therapeutics, MYOR, Novartis, Pfizer, Polyfins Techology, Regeneron, Sanofi Genzyme, Skin Actives Scientific, SUN Pharma, Target-PharmaSolutions, and UCB. Dr Chamberlain is a medical advisor and/or investigator for Aslan Pharmaceuticals, Beyeonics, Cambium, Kowa, LEO Pharma, Noveome, Oyster Point, Regeneron, and Trefoil Therapeutics. Dr Siegfried receives contracted research fees, consulting fees, honoraria, and/or is an investigator for AbbVie, AI Therapeutics, ASLAN Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, Incyte, Janssen, LEO Pharma, Novan, Novartis, Pierre Fabre, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Verrica; and is a member of the Research Advisory Committee of the National Eczema Association. Dr Cooper has served as an advisory board member for LEO Pharma and as a speaker for Pfizer. Dr Beckman reports research grants/funding from Aerie, Alcon, Allergan, Avellino, Bausch & Lomb, BioTissue, Bruder, Dompe, Eyepoint, Eyevance, Glaukos, Glint, Johnson & Johnson, Kala, LEO Pharma, Novartis, Ocular Science, Ocular Therapeutix, Sun, TearLab, Visus, and Zeiss. Dr Lio reports research grants/funding from AbbVie, AOBiome, and Regeneron/Sanofi Genzyme; is on the speaker's bureau for Eli Lilly, Galderma, Incyte, LEO Pharma, L'Oreal, Pfizer, and Regeneron/Sanofi Genzyme; and reports consulting/advisory boards for AbbVie, Almirall, Altus Labs (stock options), Amyris, AOBiome, Arbonne, ASLAN Pharmaceuticals, Bodewell, Burt's Bees, Dermavant, Eli Lilly, Exeltis, Galderma, IntraDerm, Johnson & Johnson, LEO Pharma, L'Oreal, Menlo Therapeutics, Micreos (stock options), Pfizer, Pierre-Fabre, Realm Therapeutics, Regeneron/Sanofi Genzyme, Theraplex, and Unilever. In addition, Dr Lio has a patent pending for a Theraplex product with royalties paid, and is a Board member and Scientific Advisory Committee Member of the National Eczema Association. Dr Paller is an investigator (contract to institution) for AbbVie, AnaptysBio, Eli Lilly, Incyte, Janssen, KrystalBio, Regeneron, and UCB; consultant with honorarium for Abbvie, Abeona, Alcimed, Almirall, Amagma, Anaptysbio, Arena, Azitra, BiomX, Boehringer Ingeheim, Castle Biosciences, Catawba, Dermira, Eli Lilly, Exicure, Forte, Kamari, LEO Pharma, Lifemax, NAOS, Novartis, Pfizer, Phoenix, Pierre Fabre, Regeneron, Sanofi/Genzyme, Seanergy, Trifecta, and UCB; and is on the Data Safety Monitoring Board for AbbVie, Bausch, Galderma, and Novan. Dr Simpson reports grants and/or personal fees from AbbVie, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, FortéBio, Galderma, Incyte, Kyowa Kirin, LEO Pharma, MedImmune, Menlo Therapeutics, Merck, Novartis, Ortho Dermatologics, Pfizer, Pierre Fabre Dermo Cosmetique, Regeneron, Sanofi, Tioga, and Valeant., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is characterized by T H 2-dominated skin inflammation and systemic response to cutaneously encountered antigens. The T H 2 cytokines IL-4 and IL-13 play a critical role in the pathogenesis of AD. The Q576->R576 polymorphism in the IL-4 receptor alpha (IL-4Rα) chain common to IL-4 and IL-13 receptors alters IL-4 signaling and is associated with asthma severity., Objective: We sought to investigate whether the IL-4Rα R576 polymorphism is associated with AD severity and exaggerates allergic skin inflammation in mice., Methods: Nighttime itching interfering with sleep, Rajka-Langeland, and Eczema Area and Severity Index scores were used to assess AD severity. Allergic skin inflammation following epicutaneous sensitization of mice 1 or 2 IL-4Rα R576 alleles (QR and RR) and IL-4Rα Q576 (QQ) controls was assessed by flow cytometric analysis of cells and quantitative RT-PCR analysis of cytokines in skin., Results: The frequency of nighttime itching in 190 asthmatic inner-city children with AD, as well as Rajka-Langeland and Eczema Area and Severity Index scores in 1116 White patients with AD enrolled in the Atopic Dermatitis Research Network, was higher in subjects with the IL-4Rα R576 polymorphism compared with those without, with statistical significance for the Rajka-Langeland score. Following epicutaneous sensitization of mice with ovalbumin or house dust mite, skin infiltration by CD4 + cells and eosinophils, cutaneous expression of Il4 and Il13, transepidermal water loss, antigen-specific IgE antibody levels, and IL-13 secretion by antigen-stimulated splenocytes were significantly higher in RR and QR mice compared with QQ controls. Bone marrow radiation chimeras demonstrated that both hematopoietic cells and stromal cells contribute to the mutants' exaggerated allergic skin inflammation., Conclusions: The IL-4Rα R576 polymorphism predisposes to more severe AD and increases allergic skin inflammation in mice., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Ruxolitinib cream demonstrated safety and efficacy over 8 weeks in 2 double-blind phase 3 atopic dermatitis studies (NCT03745638/NCT03745651)., Objective: To evaluate long-term safety (LTS) and disease control with ruxolitinib cream., Methods: Patients initially randomized to twice-daily 0.75%/1.5% ruxolitinib cream maintained their regimen during the 44-week LTS period (as-needed treatment). Patients on vehicle were rerandomized (1:1) at week 8 to either ruxolitinib cream strength. Safety and disease control (Investigator's Global Assessment score 0/1 and affected body surface area) were assessed., Results: Over 52 weeks, adverse events were reported in 67.4%/62.6%/53.5%/57.6% of patients in 0.75%/1.5% ruxolitinib cream/vehicle to 0.75% ruxolitinib cream/vehicle to 1.5% ruxolitinib cream groups (n = 426/446/101/99). Most common adverse events were upper respiratory tract infection (10.3%/11.4%/5.9%/7.1%) and nasopharyngitis (8.9%/9.9%/7.9%/14.1%). Most adverse events were considered unrelated to treatment. Application site reactions were infrequent (3.8%/1.8%/1.0%/1.0%). Disease control was achieved throughout the LTS; 74.1% to 77.8% of patients had Investigator's Global Assessment 0/1 at week 52, and mean affected body surface area was low (1.4%-1.8%)., Limitations: LTS had no control treatment., Conclusion: During 44 weeks of as-needed treatment, ruxolitinib cream demonstrated effective disease control and tolerability; low ruxolitinib plasma concentrations alongside safety findings reflecting known risk factors suggest physiologically meaningful systemic Janus kinase inhibition is highly unlikely., Competing Interests: Conflicts of interest KP has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite, Celgene, Coherus, Dermira, Dow Pharmaceuticals, EliLilly, Galderma, Gilead, GlaxoSmithKline, Incyte Corporation, InflaRx, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, Merck (MSD), Merck Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharmaceuticals, Takeda, and UCB. JCS has served as an advisor for AbbVie, LEO Pharma, Menlo Therapeutics, Novartis, Pierre Fabre, and Trevi; has received speaker honoraria from AbbVie, EliLilly, Janssen-Cilag, LEO Pharma, Novartis, Sanofi-Genzyme, and Sun Pharma; 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. LK has served as an investigator, consultant, or speaker for AbbVie, Amgen, Anaptys, Arcutis, Dermavant, Eli Lilly, Glenmark, Incyte Corporation, Kamedis, LEO Pharma, L'Oreal, Menlo Therapeutics, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and Taro. DT has served as an investigator for AbbVie, Amgen, Arcutis, Astellas, Astion, Avillion, Boehringer Ingelheim, Celgene, Dermira, DS BioPharma, Dow Pharmaceuticals, Eli Lilly, F. Hoffmann-La Roche Ltd, Galderma, GlaxoSmithKline, Incyte Corporation, Isotechnika, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, and UCB Biopharma. LFE has served as an investigator, consultant, speaker, or data safety monitoring board member for AbbVie, Almirall, Arcutis, Arena, Aslan, Dermavant, Eli Lilly, Forte, Galderma, Ichnos/Glenmark, Incyte Corporation, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Otsuka, Pfizer, Regeneron, and Sanofi Genzyme.SBF has received honoraria, clinical research grants, or fees as a consultant, speaker, advisory board member, and/or investigator for AbbVie, Aclaris Therapeutics, Asana BioSciences, AstraZeneca, Athenex, Celgene Corporation, Cutanea Life Sciences, EliLilly, Incyte Corporation, Innovaderm Research, Novartis, Pfizer, Promius Pharma, Regeneron, UCB, Valeant Pharmaceuticals North America, and XBiotech. MEK was an employee and shareholder of Incyte Corporation at the time of the study. HK, KS, and HR are employees and shareholders of Incyte Corporation. ELS is an investigator for AbbVie, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, Merck, Pfizer, and Regeneron and is a consultant with honorarium for AbbVie, Eli Lilly, Forte, Galderma, Incyte Corporation, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and Valeant., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest AB has served as a speaker/received honoraria from AbbVie and UCB, served as a scientific adviser/received honoraria from AbbVie, Abcentra, Aligos, Almirall, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly and Company, Evommune, Forte, Galderma, HighlightII Pharma, Incyte Corporation, Janssen, Landos, LEO Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, UCB Pharma, Vibliome, and Xencor, and has acted as a clinical study investigator/received institutional clinical study funds from AbbVie, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Galderma, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma. JCS has served as an advisor for AbbVie, LEO Pharma, Novartis, Pierre Fabre, Menlo Therapeutics, and Trevi; has received speaker honoraria from AbbVie, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, Sanofi Genzyme, and Sun Pharma; and has received clinical trial funding from AbbVie, Almirall, Amgen, Galapagos, Holm, Incyte, InflaRX, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Trevi, and UCB. KP has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite, Celgene, Coherus, Dermira, Dow Pharmaceuticals, Eli Lilly, Galderma, Gilead, GlaxoSmithKline, Incyte, InflaRx, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, Merck (MSD), Merck Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharmaceuticals, Takeda, and UCB. ELS is an investigator for AbbVie, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, Merck, Pfizer, and Regeneron and is a consultant with honorarium for AbbVie, Eli Lilly, Forte, Galderma, Incyte, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and Valeant. JIS received honoraria for advisory board, speaker, and consultant services from AbbVie, Asana, Bluefin, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Realm, Regeneron, and Sanofi and research grants for investigator services from Galderma and GlaxoSmithKline. BSK has served as a consultant to AbbVie, Almirall, Amagma, Cara Therapeutics, Daewoong, Incyte, OM Pharma, and Pfizer; has served on advisory boards for AstraZeneca, Boehringer Ingelheim, Cara Therapeutics, Celgene Corporation, Regeneron Pharmaceuticals, Sanofi Genzyme, and Trevi Therapeutics; is a shareholder in Locus Biosciences; and has a pending patent for JAK inhibitors in chronic itch. SGK is an advisory board member/consultant for AbbVie, Celldex Therapeutics, Galderma, Incyte, Johnson & Johnson, Kiniksa Pharmaceuticals, Novartis, Pfizer, Regeneron, and Sanofi and has served as an investigator for Galderma, Pfizer, and Sanofi. MEK and MEV were employees and shareholders of Incyte at the time of these studies. SW is an employee and shareholder of Incyte. LK has served as an investigator, consultant, or speaker for AbbVie, Amgen, Anaptys, Arcutis, Dermavant, Eli Lilly, Glenmark, Incyte, Kamedis, LEO Pharma, L'Oreal, Menlo Therapeutics, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and Taro.

Background: Additional long-term treatments are needed for moderate-to-severe atopic dermatitis (AD). An ongoing, open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses tralokinumab plus optional topical corticosteroids in participants from previous tralokinumab parent trials (PTs) with moderate-to-severe AD., Objective: To evaluate the safety and efficacy of up to 2 years tralokinumab treatment in a post hoc interim analysis., Methods: Safety analyses included adults from completed PTs enrolled in ECZTEND, regardless of tralokinumab exposure duration. Efficacy analyses included adult participants treated with tralokinumab in ECZTEND for ≥1 year and subgroup analyses of those on tralokinumab for 2 years (1 year from PT, 1 year in ECZTEND). Primary end point was the number of adverse events with additional efficacy end points., Results: Participants on tralokinumab had an exposure-adjusted rate of 237.8 adverse events/100 patient-years' exposure (N = 1174) in the safety analysis set. Exposure-adjusted incidence rates of common adverse events were comparable to PTs, although at lower rates. With 2 years of tralokinumab, improvements in extent and severity of AD were sustained, with Eczema Area and Severity Index (EASI-75) in 82.5% of participants (N = 345)., Limitations: Possible selection bias; no placebo arm; some participants experienced treatment gaps between PTs and ECZTEND., Conclusion: Over 2 years, tralokinumab was well tolerated and maintained long-term control of AD signs and symptoms., Competing Interests: Conflicts of interest Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, and Vibliome. Langley has served and received compensation in the form of grants and/or honoraria as principal investigator for and is on the scientific advisory board or has served as a speaker for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, and UCB. Lacour has received grants or honoraria as an investigator, advisory board member, or speaker from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Janssen, Lilly, LEO Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Toth has served as an investigator for AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, UCB, and Valeant. Laquer has received grants from AbbVie, Eli Lilly, Galderma, LEO Pharma, and Novartis. Beissert has served an advisory board member or received speaker honoraria from AbbVie Deutschland & Co, Actelion Pharmaceuticals, Almirall-Hermal, Amgen, BMS, Celgene, Galderma, GSK, Hexal-Sandoz, Janssen-Cilag, LEO Pharma, Lilly Deutschland, Menlo Therapeutics, MSD Sharp & Dohme, Novartis, Pfizer, Roche-Posay, Sanofi-Aventis Deutschland, and UCB Pharma. Wollenberg has received grants, personal fees, or nonfinancial support from AbbVie, Almirall, Beiersdorf, Bioderma, Chugai, Galapagos, Galderma, Hans Karrer, LEO Pharma, Lilly, L'Oreal, Maruho, MedImmune, Novartis, Pfizer, Pierre Fabre, Regeneron, Santen, and Sanofi-Aventis. Herranz has served as a consultant, speaker, or investigator for Amgen, Janssen, LEO Pharma, Lilly, Novartis, Parexel, Pfizer, and Sanofi. Pink reports personal fees and nonfinancial support from LEO Pharma, Novartis, and UCB and personal fees from AbbVie, Almirall, Amgen, BMS, Boehringer, Janssen, La Roche-Posay, Lilly, Pfizer, and Sanofi. Peris reports grants or personal fees for participation in advisory boards from AbbVie, Almirall, Galderma, Lilly, LEO Pharma, Novartis, Pierre Fabre, Sanofi, Sun Pharma, and Janssen. Fangel, Gjerum, and Corriveau are employees of LEO Pharma. Saeki has received lecture fees from Kyorin, Kyowa Kirin, LEO Pharma, Mitsubishi Tanabe, Maruho, Sanofi, Tokiwa, and Taiho and scholarship donations from Esai, Mitsubishi Tanabe, Maruho, and Torii. Warren has received research grants or consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, Eli Lilly, GSK, Janssen, LEO Pharma, Medac, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and UNION. He is supported by the Manchester NIHR Biomedical Research Centre. Simpson reports grants and/or personal fees from AbbVie, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, FortéBio, Galderma, Incyte, Kyowa Kirin, LEO Pharma, MedImmune, Menlo Therapeutics, Merck, Novartis, Ortho Dermatologics, Pfizer, Pierre Fabre Dermo Cosmetique, Regeneron, Sanofi, Tioga, and Valeant. Reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Forward Pharma, Gilead, Galderma, Janssen-Cilag, Kyowa Kirin, LEO, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, and UCB. Professor Reich is cofounder of Moonlake Immunotherapeutics., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Acne is the most frequent adverse event associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis., Objective: To characterize the adverse event of acne associated with upadacitinib., Methods: This was a post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials of upadacitinib, alone (NCT03569293 and NCT03607422) or in combination with topical corticosteroids (NCT03568318). Data included were from the 16-week placebo-controlled period., Results: Over 16 weeks, 84 of 857 (9.8%), 131 of 864 (15.2%), and 19 of 862 (2.2%) patients randomized to receive upadacitinib 15 mg, upadacitinib 30 mg, and placebo, respectively, experienced acne. All cases of acne, except 1, were mild/moderate in severity; 2 patients discontinued treatment due to moderate acne. Acne occurred at higher rates among younger, female, and non-White patients. Acne required no intervention in 40.5% and 46.6% of patients receiving upadacitinib 15 and 30 mg, respectively; most remaining cases were managed with topical antibiotics, benzoyl peroxide, and/or retinoids. Acne also had no impact on patient-reported outcomes., Limitations: This study was relatively short in duration and had a small patient population., Conclusions: Acne associated with upadacitinib for atopic dermatitis treatment is usually mild/moderate in severity and managed with topical therapies or no intervention., Competing Interests: Conflicts of interest Dr Mendes-Bastos has received honoraria for consulting and/or speaker services from AbbVie, Novartis, Janssen, LEO Pharma, Almirall, Sanofi, Viatris, L’Oreal, and Cantabria Labs. He has also worked as a principal investigator in clinical trials supported by AbbVie, Sanofi, and Novartis. Dr Guttman-Yassky is employed by Mount Sinai and is a researcher and/or consultant for AbbVie, Anacor Pharmaceuticals, AnaptysBio, Asana Biosciences, Botanix Pharmaceuticals, Celgene, DBV Technologies, Dermira, Dr Reddy’s Laboratories (Promius Pharma), DS Biopharma, Escalier Biosciences, Galderma, Glenmark, Innovaderm, Janssen, Kyowa Kirin, LEO Pharma, Lilly, MedImmune, Mitsubishi Tanabe Pharma, Novan, Novartis, Pfizer, Ralexar Therapeutics, Regeneron, Sanofi, Stiefel/GlaxoSmithKline, UCB, and Vitae Pharmaceuticals. Ms Jiang, Dr Ladizinski, Dr Liu, Dr Teixeira, and Dr Vigna are full-time employees of AbbVie and may hold AbbVie stock or stock options. Dr Prajapati has served as an investigator for AbbVie, Amgen, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Nimbus Lakshmi, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB Pharma, and Valeant. He has served as a consultant, advisor, and/or speaker for AbbVie, Actelion, Amgen, Aralez, Arcutis, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Janssen, LEO Pharma, L’Oreal, Medexus, Novartis, Pediapharm, Pfizer, Sanofi Genzyme, Sun Pharma, Tribute, UCB Pharma, and Valeant. Dr Simpson has received grants, personal fees, and/or nonfinancial support from AbbVie, Amgen, Arena Pharmaceuticals, BenevolentAI Bio, BiomX, Bluefin Biomedicine, Boehringer Ingelheim, Boston Consulting Group, Collective Acumen, Coronado, Dermira, Evidera, ExcerptaMedica, Forte Biosciences, Incyte, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Medscape, Merck, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi-Genzyme, SPARC India, Tioga Pharmaceuticals, and Vanda Pharmaceuticals. He has also served on advisory boards for AMAZE, FRED, Harmonising Outcome Measures for Eczema (HOME), Janssen, Kyowa Kirin, LEO Pharma, Lilly, National Eczema Association, NIH MOSS Special Emphasis Panel Study Section, Pfizer, and TARGET PharmaSolutions. Dr Barbarot has received personal fees from AbbVie, Almirall, Janssen, LEO Pharma, Lilly, Pfizer, Sanofi-Genzyme, and UCB; nonfinancial support from Novartis; and grants from LEO Pharma., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of atopic dermatitis on families of pediatric patients., Study Design: This cross-sectional, web-based survey of children/adolescents (6 months to <18 years old) with atopic dermatitis and their parents and caregivers was conducted in 18 countries encompassing North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Children and adolescents with atopic dermatitis and their parents and caregivers were identified by the International Study of Asthma and Allergies in Childhood criteria and ever being told by a physician that they had "eczema". Atopic dermatitis severity was assessed using the Patient-Oriented Eczema Measure and the Patient Global Assessment. Atopic dermatitis impact on families' lives was evaluated using the Dermatitis Family Impact questionnaire and stand-alone questions on hours of atopic dermatitis-related care (past week) and missed work days (past 4 weeks) owing to their child's atopic dermatitis., Results: A total of 7465 pairs of pediatric participants with atopic dermatitis and their parents or caregivers were surveyed. Across age groups, the Dermatitis Family Impact questionnaire total score for all regions ranged from 7.1 to 8.6, 13.2 to 14.9, and 17.0 to 17.2 for Patient-Oriented Eczema Measure mild, moderate, and severe atopic dermatitis, respectively. Subscale scores showed that greater atopic dermatitis severity had a greater impact on all family life domains, including sleep and tiredness. No specific patterns or trends were observed across age groups. Time spent on childcare and missed work days increased with atopic dermatitis severity., Conclusions: Across pediatric age groups and geographic regions, greater atopic dermatitis severity was associated with a greater negative impact on physical, emotional, social, and economic components of family life., (Copyright © 2022. Published by Elsevier Inc.)

Core outcome sets are critically important outcomes that should be measured in clinical trials. Their absence in atopic dermatitis is a form of research waste and impedes combining evidence to inform patient care. Here, we articulate the rationale for core outcome sets in atopic dermatitis and review the work of the international Harmonising Outcome Measures for Eczema group from its inception in Munich, 2010. We describe core domain determination (what should be measured), to instrument selection (how domains should be measured), culminating in the complete core outcome measurement set in Tokyo, 2019. Using a "road map," Harmonising Outcome Measures for Eczema includes diverse research methods including Delphi and nominal group techniques informed by systematic reviews of properties of candidate instruments. The 4 domains and recommended instruments for including in all clinical trials of atopic dermatitis are patient symptoms, measured by Patient-Oriented Eczema Measure and peak Numerical Rating Scale 11 for itch intensity over 24 hours, clinical signs measured using the Eczema Area and Severity Index, quality of life measured by the Dermatology Life Quality Index series for adults, children, and infants, and long-term control measured by either Recap of atopic eczema or Atopic Dermatitis Control Tool., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, skin pain, and sleep disturbances. Currently, dupilumab is the only systemic therapy and biologic medication approved by the United States Food and Drug Administration for moderate-to-severe AD in adults and children. There is a sparsity of literature available on determining treatment failure with dupilumab and the next steps health care providers can take to treat AD. Individual goals and quality of life and not just body surface area should be considered when defining treatment failure. Possible confounding dermatoses also should be ruled out. Early identification of dupilumab-induced adverse events is important. For most patients, dupilumab can be continued while treatment for the adverse event is initiated. Adjusting the frequency of dupilumab dosing also may be considered in some circumstances. Adjuvant therapies, such as methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, or phototherapy can be added but the safety and efficacy of these combination treatments are not known at this time., Competing Interests: Conflicts of interest Dr Narla has no conflicts of interest to report. Dr Silverberg has received honoraria as a consultant and/or advisory board member for Abbvie, Afyx, Arena, Asana, BioMX, Bluefin, Bodewell, Boehringer-Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo, Luna, Menlo, Novartis, Pfizer, RAPT, Regeneron, Sanofi; data safety monitoring committee member for Afyx, Hoth, Morphosys; speaker for Pfizer, Regeneron, Sanofi-Genzyme; and Dr Silverberg's institution received grants from Galderma. Dr Simpson reports grants and fees for participation as a consultant and principal investigator for Eli Lilly and Company, LEO Pharma, Pfizer, and Regeneron; grants for participation as a principal investigator from Galderma and Merck; and fees for consultant services from AbbVie, Boehringer-Ingelheim, Dermavant Incyte, Forte Bio, Pierre Fabre Dermo, and Sanofi-Genzyme., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility., Objective: We evaluated the maintenance of abrocitinib-induced response with continuous abrocitinib treatment, dose reduction or withdrawal, and response to treatment reintroduction following flare (JAK1 Atopic Dermatitis Efficacy and Safety [JADE] REGIMEN: National Clinical Trial 03627767)., Methods: Patients with moderate-to-severe atopic dermatitis responding to open-label abrocitinib 200 mg monotherapy for 12 weeks were randomly assigned in a 1:1:1 ratio to blinded abrocitinib (200 or 100 mg) or placebo for 40 weeks. Patients experiencing flare received rescue treatment (abrocitinib 200 mg plus topical therapy)., Results: Of 1233 patients, 798 responders to induction (64.7%) were randomly assigned. The flare probability during maintenance was 18.9%, 42.6%, and 80.9% with abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Among patients with flare in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, 36.6%, 58.8%, and 81.6% regained investigator global assessment 0/1 response, respectively, and 55.0%, 74.5%, and 91.8% regained eczema area and severity index response, respectively, with rescue treatment. During maintenance, 63.2% and 54.0% of patients receiving abrocitinib 200 and 100 mg, respectively, experienced adverse events., Limitations: The definition of protocol-defined flare was not established, limiting the generalizability of findings., Conclusion: Induction treatment with abrocitinib was effective; most responders continuing abrocitinib did not flare. Rescue treatment with abrocitinib plus topical therapy effectively recaptured response., Competing Interests: Conflicts of interest Dr Blauvelt has served as a scientific adviser and/or clinical study investigator for Pfizer, AbbVie, Aligos, Almirall, Amgen, Arcutis, Arena, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, RAPT, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma. Dr Silverberg has served as an investigator for AbbVie, Eli Lilly, Galderma, Kiniksa, LEO Pharma, and Trevi; as a consultant or advisory board member for Pfizer Inc, AbbVie, AFYX, Arena, Asana, BiomX, Bluefin, Bodewell, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo, Luna, Menlo, Novartis, RAPT, Regeneron, and Sanofi; and as a speaker for Pfizer, Regeneron, and Sanofi. Dr Lynde has served as a principal investigator, consultant, and/or speaker for Pfizer Inc, AbbVie, Bausch Health (Valeant), Celgene, Eli Lilly, Janssen, LEO Pharma, and Novartis. Dr Bieber is a lecturer and/or consultant for Pfizer Inc, AbbVie, Almirall, AnaptysBio, Arena Pharmaceuticals, Asana Biosciences, BioVersys, Boehringer Ingelheim, Daiichi Sankyo, Dermavant Roivant, Eli Lilly, Galapagos/MorphoSys, Galderma, Glenmark, GSK, Incyte, Kymab, Leo, La Roche-Posay, Menlo Therapeutics, Novartis, RAPT, Sanofi Regeneron, UCB, and Vectans Pharma and an investigator for AFYX (DermTreat). Dr Eisman has been an investigator in clinical trials for Pfizer Inc, AbbVie, Arena, Boston Pharmaceuticals, Bristol Myers Squibb, Botanix, Dermira, Eli Lilly, Leo, Novartis, Regeneron, and Suzhou Connect Biopharmaceuticals. Dr Zdybski has been an investigator for clinical trials for Pfizer, Trevi Pharmaceuticals, and Regeneron. Dr Gubelin has served as a scientific adviser and/or clinical study investigator for Pfizer, Galderma, GSK, Eucerin, Johnson & Johnson, Janssen, Sanofi, BioNOOX, and Beiersdorf/Eucerin. Dr Simpson reports grants from Pfizer Inc, Eli Lilly, Kyowa Kirin, Leo, Merck, and Regeneron and personal fees from Pfizer Inc, Bausch Health (Valeant), Dermira, Eli Lilly, Galderma, Leo, Menlo Therapeutics, Novartis, Regeneron, and Sanofi Genzyme. Dr Valenzuela has served as a scientific adviser and/or clinical study investigator for Pfizer, AbbVie, Amgen, Eli Lilly, Galderma, Janssen, Leo, Merck, Novartis, and Sanofi Genzyme. Dr Criado reports grants from Abbott, Takeda, Novartis, and Pfizer. Dr Lebwohl is an employee of Mount Sinai, which receives research funds from AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen Research & Development, Leo, Ortho Dermatologics, Pfizer, and UCB and is a consultant for Aditum Bio, Allergan, Almirall, Arcutis, Avotres Therapeutics, BirchBioMed, BMD Skincare, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Leo, Meiji Seika Pharma, Menlo, Mitsubishi Tanabe Pharma, Neuroderm, Pfizer, Promius/Dr. Reddy's Laboratories, Serono, Theravance, and Verrica. Drs Feeney, Khan, Biswas, DiBonaventura, Valdez, and Rojo are employees and shareholders of Pfizer Inc. Dr Cameron is a former employee and current shareholder of Pfizer Inc., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Ruxolitinib (RUX) cream demonstrated potent anti-inflammatory and antipruritic efficacy in a phase 2 study in adults with atopic dermatitis (AD)., Objective: To evaluate 8-week efficacy and safety in 2 phase 3 studies of RUX cream in patients with AD., Methods: Topical Ruxolitinib Evaluation in Atopic Dermatitis Study 1 (NCT03745638) and Study 2 (NCT03745651) enrolled patients aged ≥12 years with AD for ≥2 years, an Investigator's Global Assessment score of 2/3, and 3%-20% affected body surface area. Patients were randomized 2:2:1 to twice-daily 0.75% RUX cream, 1.5% RUX cream, or vehicle cream for 8 continuous weeks. The primary endpoint was Investigator's Global Assessment treatment success at week 8 (Investigator's Global Assessment score of 0/1 and ≥2-grade improvement from baseline)., Results: In the Topical Ruxolitinib Evaluation in Atopic Dermatitis Study 1 and 2, 631 and 618 patients were randomized (631/577 analyzed for efficacy). Significantly more patients achieved Investigator's Global Assessment treatment success with 0.75% RUX cream (50.0%/39.0%) and 1.5% RUX cream (53.8%/51.3%) versus vehicle (15.1%/7.6%; P < .0001) at week 8. Significant itch reductions versus vehicle were reported within 12 hours of first application of 1.5% RUX (P < .05). Application site reactions were infrequent (<1%) and lower with RUX versus vehicle; none were clinically significant., Limitations: Longer-term safety data are not yet available., Conclusions: RUX cream showed anti-inflammatory and prompt antipruritic effects with superior efficacy versus vehicle and was well tolerated., Competing Interests: Conflicts of interest Dr Papp has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or Steering Committee member for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite, Celgene, Coherus, Dermira, Dow Pharmaceuticals, Eli Lilly, Galderma, Genentech, Gilead, GlaxoSmithKline, Incyte Corporation, InflaRx, Janssen, Kyowa Hakko Kirin, LEO, Medimmune, Meiji Seika Pharma, Merck (MSD), Merck Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharmaceuticals, Takeda, and UCB. Dr Szepietowski has served as an advisor for AbbVie, LEO Pharma, Novartis, Pierre Fabre, Menlo Therapeutics, and Trevi; has received speaker honoraria from AbbVie, Janssen-Cilag, LEO Pharma, Novartis, Sanofi-Genzyme, Sun Pharma, and Eli Lilly; 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. Dr Kircik has served as an investigator, consultant, or speaker for AbbVie, Amgen, Anaptys, Arcutis, Dermavant, Eli Lilly, Glenmark, Incyte Corporation, Kamedis, LEO Pharma, L’Oréal, Menlo, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and Taro. Dr Toth has served as an investigator for AbbVie, Avillion, Amgen, Arcutis, Astellas, Astion, Boehringer Ingelheim, Celgene, Dermira, DS BioPharma, Dow Pharmaceuticals, Eli Lilly, F. Hoffmann-La Roche Ltd, Galderma, GlaxoSmithKline, Incyte Corporation, Isotechnika, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, and UCB Biopharma. Dr Eichenfield has served as an investigator, consultant, speaker, or data safety monitoring board member for AbbVie, Almirall, Arcutis, Dermira, Eli Lilly, Forte Biosciences, Galderma, Ichnos/Glenmark, Incyte Corporation, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Otsuka, Pfizer, Regeneron, and Sanofi Genzyme. Dr Leung has served as an advisor, investigator, or speaker for Incyte Corporation, LEO Pharma, Boehringer Ingelheim, Genentech, Aimmune, Novartis, Sanofi, and Regeneron. Dr Forman has received honoraria, clinical research grants, or fees as a consultant, speaker, advisory board member, and/or investigator for AbbVie, Aclaris Therapeutics, Asana BioSciences, AstraZeneca, Athenex, Celgene Corporation, Cutanea Life Sciences, Eli Lilly, Incyte Corporation, Innovaderm Research, Novartis, Pfizer, Promius Pharma, Regeneron, UCB, Valeant Pharmaceuticals North America, and XBiotech. Drs Venturanza, Sun, and Kuligowski are employees and shareholders of Incyte Corporation. Dr Simpson is an investigator for AbbVie, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, Merck, Pfizer, and Regeneron and is a consultant with honorarium for AbbVie, Eli Lilly, Forte Bio, Galderma, Incyte Corporation, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and Valeant., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Baricitinib, an oral selective Janus kinase 1/Janus kinase 2 inhibitor, is being studied for moderate-to-severe atopic dermatitis (AD) in adults., Objective: To evaluate the efficacy and safety of baricitinib monotherapy in a North American phase 3 trial (BREEZE-AD5/NCT03435081) of adults with moderate-to-severe AD who responded inadequately or were intolerant to topical therapy., Methods: Patients (N = 440) were randomized 1:1:1 to once-daily placebo or baricitinib (1 mg or 2 mg). The primary endpoint was the proportion of patients achieving ≥75% reduction in the Eczema Area and Severity Index at week 16. A key secondary endpoint was the proportion of patients achieving a validated Investigator Global Assessment for AD score of 0 (clear)/1(almost clear) with ≥2-point improvement., Results: At week 16, the proportion of patients achieving Eczema Area and Severity Index was 8%, 13%, and 30% (P < .001, 2 mg vs placebo) and those with a validated Investigator Global Assessment for AD score of 0/1 were 5%, 13%, and 24% (P < .001, 2 mg vs placebo) for placebo, baricitinib 1 mg, and baricitinib 2 mg, respectively. Safety findings were similar to those of other baricitinib AD studies., Limitations: Short-term clinical trial results may not be generalizable to real-world settings., Conclusion: Baricitinib was efficacious for patients with moderate-to-severe AD with no new safety findings over 16 weeks., Competing Interests: Conflicts of interest Dr Simpson reports grants and fees for participation as a consultant and principal investigator from Eli Lilly and Company, LEO Pharma, Pfizer, and Regeneron; grants for participation as a principal investigator from Galderma and Merck & Co; and fees for consultant services from AbbVie, Boehringer Ingelheim, Dermavant Incyte, Forte Bio, Pierre Fabre Dermo, and Sanofi Genzyme. Dr Forman is a consultant, investigator, advisory board member, and/or speaker for and receives funding and/or honoraria from AbbVie, Aclaris Therapeutics Inc, Asana BioSciences, AstraZeneca, Athenex, Celgene Corporation, Cutanea Life Sciences, Eli Lilly and Company, Incyte Corporation, Innovaderm Research Inc, Novartis, Pfizer Inc, Promius Pharma LLC, Regeneron, UCB, Valeant Pharmaceuticals North America LLC, and XBiotech. Dr Silverberg served as a consultant and/or advisory board member for AbbVie, Arena, Asana, Bluefin, Boehringer Ingelheim, Dermavant, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa, Leo, Luna, Novartis, Pfizer, RAPT, Regeneron, and Sanofi, receiving honoraria; served as a speaker for Regeneron-Sanofi; and received research grants from Galderma. Dr Zirwas is a consultant, investigator, and/or speaker for Regeneron, Sanofi, Genench, Novartis, L'Oreal, Menlo, Leo, Eli Lilly and Company, Ortho Derm, and Arcutis and is a part owner of AsepticMD. Dr Han is a consultant for Eli Lilly and Company, Regeneron, Sanofi, and Pfizer. Dr Guttman-Yassky is a consultant for AbbVie, Almirall, Amgen, Asana Biosciences, Boehringer Ingelhiem, Cara Therapeutics, Celgene, Concert, DBV, Dermira, DS Biopharma, Eli Lilly and Company, EMD Serono, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Mitsubishi Tanabe, Pfizer, RAPT Therapeutics, Regeneron, Sanofi, Sienna Biopharma, and Union Therapeutics and reports institute grants for research from AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, Boehringer Ingelhiem, Celgene, Dermavant, DS Biopharma, Eli Lilly and Company, Glenmark, Galderma, Innovaderm, Janssen, Kiniska, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Ralexar, Regeneron, Sienna Biopharma, UCB, and Union Therapeutics. Dr Bissonnette is an advisory board member, consultant, speaker and/or investigator for and receives honoraria and/or grant from AbbVie, Arcutis, Arena Pharma, Asana BioSciences, Bellus Health, Boehringer Ingelheim, CARA, Dermavant, Eli Lilly, EMD Serono, Galderma, Incyte, Kiniksa, Kyowa Kirin, LEO Pharma, Novan, Pfizer, Ralexar, RAPT, Regeneron, Sanofi Genzyme, and Sienna and is an employee and shareholder of Innovaderm Research. Dr Waibel is an investigator, consultant speaker for, and/or receives honoraria from AbbVie, Pfizer, Candela, Cytrellis, Dominion, Eli Lilly and Company, Novartis, Sebacia, and Sciton. Dr Papp is a consultant, speaker, investigator, scientific officer, steering committee member, and/or advisory board member for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly and Company, Evelo, Galapagos, Galderma, Genentech, Gilead, GSK, Janssen, Kyowa Hakko Kirin, Leo, Medimmune, Meiji Seika Pharma, Merck (MSD), Merck- Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, UCB. Drs Nunes, Holzwarth, and Janes and authors DeLozier and Angle are employees and shareholders of Eli Lilly and Company. Drs Gamalo and Goldblum were employees of Eli Lilly and Company during the study. Drs Maverakis and Marnell and author Zhong have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier Inc.)

Background: Current valid instruments that measure the signs of atopic dermatitis in clinical trials may not be suitable for clinical practice because of their complexity. The product of a clinician-derived 5-point signs global assessment and body surface area (SGA × BSA) may represent a simple approach to quickly assess the severity of signs in patients with atopic dermatitis in clinical practice., Objectives: Evaluate the basic measurement properties of the SGA × BSA., Methods: Retrospective chart review of patients with atopic dermatitis treated in an outpatient dermatology clinic at Oregon Health & Science University from 2015 to 2018 who had a recorded BSA and SGA., Results: We identified 138 patients completing 325 clinic visits. SGA × BSA demonstrated strong and statistically significant (P < .001) correlations with the Eczema Area and Severity Index (r = 0.91, n = 19), average daily pruritus (r = 0.71, n = 177), patient global assessment (r = 0.74, n = 170), and a derived global scale composed of the average of 4 signs rated between 0 and 3 (r = 0.77, n = 282). Acceptability, responsiveness, and floor or ceiling effects of the measure were deemed adequate. Severity banding was maximized at 1, 21, and 87 (κ = 0.4902)., Limitations: The patient cohort was gathered exclusively from a tertiary care clinic setting in the Pacific Northwest and lacked ethnic diversity., Conclusions: The results from this study suggest that SGA × BSA is a valid and feasible instrument for atopic dermatitis signs in clinical practice., (Copyright © 2020. Published by Elsevier Inc.)

Background: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization., Objectives: To develop an IGA scale, training module, and clinical certification examination for use in AD trials; establish content validity; and assess reliability., Methods: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-AD TM ). Reliability (interrater and intrarater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and examination., Results: Expert consensus was achieved around a 5-point IGA scale including morphologic descriptions, and content validity was established. Survey 1 showed strong interrater reliability (Kendall's coefficient of concordance W [Kendall's W], 0.809; intraclass correlation [ICC], 0.817) and excellent agreement (weighted kappa, 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall's W, 0.819; ICC, 0.852; weighted kappa, 0.889). In this study, 627 investigators completed vIGA-AD training and certification., Limitations: Ratings were assessed on photographs., Conclusion: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed., (Copyright © 2020. Published by Elsevier Inc.)

Background: Pruritus (itch) is a cardinal symptom in atopic dermatitis (AD)., Objective: To evaluate the timing and effect of dupilumab on itch., Methods: Analysis of data from 1505 patients with moderate to severe AD included in 4 randomized controlled studies, treated for up to 52 weeks. Adults received dupilumab 300 mg every 2 weeks or placebo monotherapy (SOLO 1: NCT02277743; SOLO 2: NCT02277769), with concomitant topical corticosteroids (CHRONOS: NCT02260986); adolescents (≥12 to <18 y) were treated with dupilumab monotherapy every 2 weeks (200 mg for baseline weight of <60 kg; 300 mg for baseline weight of ≥60 kg) or placebo (AD ADOL: NCT03054428)., Results: Dupilumab showed significant rapid improvements from baseline in daily Peak Pruritus Numerical Rating Scale scores versus placebo, by day 2 in adults and day 5 in adolescents. At treatment end, dupilumab vs placebo/control had greater least-squares mean percent change from baseline in the weekly average of Peak Pruritus Numerical Rating Scale scores: SOLO -47.5% vs -20.5%; AD-ADOL -47.9% vs -19.0%; CHRONOS -57.3% vs -30.9% (P < .0001 for all)., Limitations: Short duration of monotherapy trials (16 weeks)., Conclusion: Across 4 randomized trials, dupilumab treatment showed rapid and sustained improvements in the magnitude of itch, starting with first dose; responses progressively increased and were sustained through to the end of treatment, up to 1 year., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Measuring patient-centered outcomes in clinical practice is valuable for monitoring patients and advancing real-world research. A new initiative from the Harmonising Outcome Measures for Eczema (HOME) group aims to recommend what might be recorded for atopic eczema patients in routine clinical care., Objectives: Prioritize outcome domains to measure atopic eczema in clinical practice and select valid and practical outcome measurement instruments for the highest-priority domain., Methods: An online survey of HOME members identified and ranked 21 possible health domains. Suitable instruments were then selected for the top-prioritized domain at the HOME VI meeting, using established consensus processes informed by systematic reviews of instrument quality., Results: Patient-reported symptoms was the top-prioritized domain. In accordance with psychometric properties and feasibility, there was consensus that the recommended instruments to measure atopic eczema symptoms in clinical practice are the POEM, the PO-SCORAD index, or both. The numeric rating scale for itch received support pending definition and validation in atopic eczema., Conclusion: Following the first step of the HOME Clinical Practice initiative, we endorse using the POEM, the PO-SCORAD index, or both for measuring atopic eczema symptoms in clinical practice. Additional high-priority domains for clinical practice will be assessed at subsequent HOME meetings., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data about the impact of narrowband ultraviolet B phototherapy on patient-reported measures of health-related quality of life., Objective: To evaluate the impact of adalimumab and phototherapy on health-related quality of life., Methods: We examined patient-reported outcomes from a multicenter, randomized, placebo-controlled trial (ClinicalTrials.gov no. NCT01553058). The Dermatology Life Quality Index and EQ-5D-3L were evaluated every 4 weeks., Results: We enrolled 97 patients: 30.9% were female, mean age was 43.5 years (standard deviation, 14.0), and median Psoriasis Area and Severity Index score was 16.7 (interquartile range, 13.9-21.6). At week 12, patients being treated with adalimumab (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.02-8.17) and phototherapy (OR, 8.83; 95% CI, 2.47-31.57) were more likely to achieve the minimal clinically important difference in the Dermatology Life Quality Index compared with those receiving placebo. There were higher odds of achieving the minimal clinically important difference for the EQ-5D-3L Index score when comparing phototherapy versus placebo (OR, 9.78; 95% CI, 2.99-31.95) and phototherapy versus adalimumab (OR, 4.07; 95% CI, 1.42-11.70)., Limitations: Small sample size, secondary analysis, generalizability., Conclusion: Phototherapy and adalimumab both improve skin-related quality of life and overall health-related quality of life compared with placebo in patients with psoriasis; however, patients treated with phototherapy achieved more improvement in overall health-related quality of life compared with patients treated with adalimumab., (Copyright © 2019 American Academy of Dermatology, Inc. All rights reserved.)

The development of core outcome sets (COSs; ie, a minimum set of core outcomes that should be measured and reported in all trials or in clinical practice for a specific condition) in dermatology is increasing in pace. A total of 44 dermatology-related COS projects have been registered in the online Core Outcome Measures in Effectiveness Trials database (http://www.comet-initiative.org/studies/search) and include studies on 26 different skin diseases. With the increasing number of COSs in dermatology, care is needed to ensure the delivery of high-quality COSs that meet quality standards when using state-of-the-art methods. In 2015, the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) was established. CS-COUSIN is an international, multidisciplinary working group aiming to improve the development and implementation of COSs in dermatology. CS-COUSIN has developed guidance on how to develop high-quality COSs for skin diseases and supports dermatology-specific COS initiatives. Currently, 17 COS development groups are affiliated with CS-COUSIN and following standardized COS development processes. To ensure successful uptake of COSs in dermatology, researchers, clinicians, systematic reviewers, guideline developers, and other stakeholders should use existing COSs in their work., (Copyright © 2019 American Academy of Dermatology, Inc. All rights reserved.)

Background: Tezepelumab (AMG 157/MEDI9929), a first-in-class monoclonal antibody, targets thymic stromal lymphopoietin, a cytokine that is implicated in the pathogenesis of atopic dermatitis (AD)., Objective: We sought to evaluate the efficacy and safety of tezepelumab in adults with moderate to severe AD., Methods: In this phase 2a study (NCT02525094), 113 patients were randomized 1:1 to subcutaneous tezepelumab 280 mg or placebo every 2 weeks, plus class 3 topical corticosteroids (TCS). The primary endpoint was the week 12 response rate for a ≥50% reduction in the Eczema Area and Severity Index (EASI50). Secondary endpoints including EASI75, Investigator's Global Assessment, SCORAD 50, SCORAD 75, pruritus numeric rating and 5-D itch scales, and exploratory endpoints (including EASI90) were assessed at weeks 12, and 16 (post hoc)., Results: A numerically greater percentage of tezepelumab plus TCS-treated patients achieved EASI50 (64.7%) versus placebo plus TCS (48.2%; P = .091). Numerical improvements over placebo were demonstrated for week 12 secondary and exploratory endpoints, with further improvements at week 16. Treatment-emergent adverse events were similar between treatment groups., Limitations: Greater than expected response rates in placebo-treated patients were possibly attributable to TCS., Conclusion: Although not statistically significant, numerical improvements over placebo for all week 12 endpoints were demonstrated, with greater week 16 responses., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling., Objectives: The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD)., Methods: In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once-daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks. Use of TCSs was permitted during the study. The primary outcome was the proportion of patients achieving at least a 50% reduction in the Eczema Area and Severity Index (EASI-50) compared with placebo., Results: Significantly more patients who received baricitinib, 4 mg, achieved EASI-50 than did patients receiving placebo (61% vs 37% [P = .027]) at 16 weeks. The difference between the proportion of patients receiving baricitinib, 2 or 4 mg, who achieved EASI-50 and the proportion of patients receiving placebo and achieving EASI-50 was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 of the patients receiving placebo (49%), 17 of those receiving 2 mg of baricitinib (46%), and 27 of those receiving 4 mg of baricitinib (71%)., Limitations: A TCS standardization period before randomization reduced disease severity, limiting the ability to compare results with those of baricitinib monotherapy. Longer studies are required to confirm baricitinib's efficacy and safety in patients with AD., Conclusions: Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate-to-severe AD., (Copyright © 2018. Published by Elsevier Inc.)

Background: The impact of dupilumab, an anti-interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown., Objectives: To assess T-cell-dependent and T-cell-independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety., Methods: In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16., Results: In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3% and 83.7%, respectively) and meningococcal polysaccharide (86.7% and 87.0%, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2% dupilumab and 34.8% placebo). Dupilumab improved key AD efficacy endpoints (P < .001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo., Limitation: Patients' prior vaccination status was not available before enrollment., Conclusion: Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis (AD)., Objective: We investigated the efficacy and safety of lebrikizumab, an IL-13 monoclonal antibody, as an add-on to topical corticosteroid (TCS) treatment., Methods: A randomized, placebo-controlled, double-blind, phase 2 study. Adults with moderate-to-severe AD were required to use TCS twice daily and then randomized (1:1:1:1) to lebrikizumab 125 mg single dose, lebrikizumab 250 mg single dose, lebrikizumab 125 mg every 4 weeks for 12 weeks, or placebo every 4 weeks for 12 weeks, after a 2-week TCS run-in. The primary endpoint was percentage of patients achieving Eczema Area and Severity Index (EASI)-50 at week 12., Results: In total, 209 patients received the study drug. At week 12, significantly more patients achieved EASI-50 with lebrikizumab 125 mg every 4 weeks (82.4%; P = .026) than placebo every 4 weeks (62.3%); patients receiving a single dose of lebrikizumab showed no statistically significant improvements in EASI-50 compared with placebo. Adverse events were similar between groups (66.7% all lebrikizumab vs 66.0% placebo) and mostly mild or moderate., Limitations: Protocol-mandated twice daily TCS treatment limits our understanding of the efficacy of lebrikizumab as a monotherapy. The short study duration did not enable long-term efficacy or safety evaluations., Conclusion: When combined with TCS, lebrikizumab 125 mg taken every 4 weeks led to a significant improvement and was well tolerated in patients with moderate-to-severe AD., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking., Objective: To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient., Methods: A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion., Results: We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy., Limitations: Our work is a consensus statement, not a systematic review., Conclusion: The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies., (Copyright © 2017 American Academy of Dermatology, Inc. All rights reserved.)

Background: The American Academy of Dermatology recommends dermatologists understand the costs of dermatologic care., Objective: This study sought to measure dermatology providers' understanding of the cost of dermatologic care and how those costs are communicated to patients. We also aimed to understand the perspectives of patients and dermatological trainees on how cost information enters into the care they receive or provide., Methods: Surveys were systematically developed and distributed to 3 study populations: dermatology providers, residents, and patients., Results: Response rates were over 95% in all 3 populations. Dermatology providers and residents consistently underestimated the costs of commonly recommended dermatologic medications but accurately predicted the cost of common dermatologic procedures. Dermatology patients preferred to know the cost of procedures and medications, even when covered by insurance. In this population, the costs of dermatologic medications frequently interfered with patients' ability to properly adhere to prescribed regimens., Limitations: The surveyed population was limited to the northwestern United States and findings may not be generalizable. Cost estimations were based on average reimbursement rates, which vary by insurer., Conclusion: Improving dermatology providers' awareness and communication of the costs of dermatologic care might enhance medical decision-making, improve adherence and outcomes, and potentially reduce overall health care expenditures., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardized methods for capturing long-term control of AD., Objective: We sought to identify how long-term control has been captured in published randomized controlled trials (RCTs). Results will initiate consensus discussions on how best to measure long-term control in the core outcome set for AD., Methods: We conducted a systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of 3 months or longer, at least 1 outcome measure recorded at 3 or more time points, full article available, and published in English., Results: In all, 101 of 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%), and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly used for trials including flare data (21/52). Medication use was recorded based on quantity, potency, and frequency of application., Limitations: We included RCT data only., Conclusion: This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies found conflicting results about whether childhood atopic dermatitis (AD) persists into adulthood., Objective: We sought to determine persistence rates and clinical factors associated with prolonged AD., Methods: A systematic review was performed in MEDLINE, EMBASE, Scopus, GREAT, LILACS, Web of Science, Academic Search Complete, and Cochrane Library. Meta-analysis was performed using Kaplan-Meier plots and random-effects proportional hazards regression., Results: In total, 45 studies including 110,651 subjects spanning 434,992 patient-years from 15 countries were included. In pooled analysis, 80% of childhood AD did not persist by 8 years and less than 5% persisted by 20 years after diagnosis (mean ± SE: 6.1 ± 0.02 years). Children with AD that persisted already for more than 10 years (8.3 ± 0.08 years) had longer persistence than those with 3 (3.2 ± 0.02 years) or 5 (6.8 ± 0.06 years) years of persistence. Children who developed AD by age 2 years had less persistent disease (P < .0001). Persistence was greater in studies using patient-/caregiver-assessed versus physician-assessed outcomes, female versus male patients (P ≤ .0006), but not in those with sensitivity to allergens (P = .90). Three studies found prolonged persistence with more severe AD., Limitations: Some studies did not capture recurrences later in life., Conclusions: Most childhood AD remitted by adulthood. However, children with already persistent disease, later onset, and/or more severe disease have increased persistence., Competing Interests: Conflicts of Interest: None declared., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks., Objective: We sought to assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766; AD-302: NCT02118792)., Methods: Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus., Results: More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P < .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P < .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity., Limitations: Short study duration was a limitation., Conclusions: Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Moderate to severe atopic dermatitis (AD) is associated with substantial patient burden despite current therapies., Objective: We sought to evaluate dupilumab treatment on patient-reported outcomes in adults with moderate to severe AD., Methods: Adults (N = 380) with moderate to severe AD inadequately controlled by topical medications were randomized to 16 weeks of double-blind, subcutaneous treatment with dupilumab 100 mg every 4 weeks, 200 mg every 2 weeks, 300 mg every 2 weeks, 300 mg once weekly, or placebo. Patient-reported outcomes included pruritus numeric rating scale; patient-reported sleep item on Scoring AD scale; Patient-Oriented Eczema Measure; Hospital Anxiety and Depression Scale; Dermatology Life Quality Index; and 5-dimension 3-level EuroQol., Results: Dupilumab reduced peak itch at 16 weeks relative to placebo by 1.1 to 3.2 points on numeric rating scale (P < .0001 all doses, except 100 mg every 4 weeks P < .05); improved sleep and health-related quality of life on Dermatology Life Quality Index and 5-dimension 3-level EuroQol (P < .05 all doses, except 100 mg every 4 weeks); and reduced anxiety and depression symptoms (P < .05 all doses). Dupilumab's effects appeared early and achieved clinically relevant improvements without significant safety concerns., Limitations: There are potential cultural differences affecting patient-reported outcome responses. Outcomes were secondary or exploratory end points., Conclusion: Dupilumab produced early and sustained patient-reported and clinically relevant improvements in sleep, mental health, and health-related quality of life; the two 300-mg dose regimens resulted in greatest benefits., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The adult burden of atopic dermatitis (AD) is poorly characterized., Objective: We sought to characterize AD burden in adults with moderate to severe disease from the patient's perspective., Methods: Patient-reported outcomes collected at screening in a phase 2b clinical trial of dupilumab included pruritus numeric rating scale, 5-Dimension Pruritus Scale, subjective components of SCORing AD, Patient-Oriented Eczema Measure, Hospital Anxiety and Depression Scale, Dermatology Life Quality Index, and 5-Dimension EuroQol., Results: Most of the 380 patients had been living with AD for nearly all their lives, whereas approximately 40% were given a diagnosis as adults; 40.3% had asthma and 60.5% had other allergic conditions. Despite 48.2% of patients using systemic therapies in the past year, patients reported problems with itch frequency (85% of patients), duration (41.5% reported itching ≥18 h/d), and severity (6.5 of 10 on numeric rating scale); 55% reported AD-related sleep disturbances 5 d/wk or more. Hospital Anxiety and Depression Scale scores suggesting clinically relevant anxiety or depression were reported by 21.8% of patients. Quality of life was impaired on Dermatology Life Quality Index and 5-dimension EuroQol., Limitations: This study had limited generalizability; conclusions may not reflect those with mild AD or not participating in a clinical trial., Conclusions: Adults with moderate to severe AD report multidimensional burden including disease activity, patient-reported symptoms, comorbidities, and quality-of-life impact., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Investigators often use global assessments to provide a snapshot of overall disease severity in dermatologic clinical trials. Although easy to perform, the frequency of use and standardization of global assessments in studies of atopic dermatitis (AD) is unclear., Objectives: We sought to assess the frequency, definitions, and methods of analysis of Investigator Global Assessment in randomized controlled trials of AD., Methods: We conducted a systematic review using all published randomized controlled trials of AD treatments in the Global Resource of Eczema Trials database (2000-2014). We determined the frequency of global scales application and defining features., Results: Among 317 trials identified, 101 trials (32%) used an investigator-performed global assessment as an outcome measure. There was large variability in global assessments between studies in nomenclature, scale size, definitions, outcome description, and analysis. Both static and dynamic scales were identified that ranged from 4- to 7-point scales. North American studies used global assessments more commonly than studies from other countries., Limitations: The search was restricted to the Global Resource of Eczema Trials database., Conclusion: Global assessments are used frequently in studies of AD, but their complete lack of standardized definitions and implementation preclude any meaningful comparisons between studies, which in turn impedes data synthesis to inform clinical decision-making. Standardization is urgently required., (Copyright © 2015. Published by Elsevier Inc.)

Background: The National Eczema Association has received increasing numbers of patient inquiries regarding "steroid addiction syndrome," coinciding with the growing presence of social media dedicated to this topic. Although many of the side effects of topical corticosteroids (TCS) are addressed in guidelines, TCS addiction is not., Objective: We sought to assess the current evidence regarding addiction/withdrawal., Methods: We performed a systematic review of the current literature., Results: Our initial search yielded 294 results with 34 studies meeting inclusion criteria. TCS withdrawal was reported mostly on the face and genital area (99.3%) of women (81.0%) primarily in the setting of long-term inappropriate use of potent TCS. Burning and stinging were the most frequently reported symptoms (65.5%) with erythema being the most common sign (92.3%). TCS withdrawal syndrome can be divided into papulopustular and erythematoedematous subtypes, with the latter presenting with more burning and edema., Limitations: Low quality of evidence, variability in the extent of data, and the lack of studies with rigorous steroid addiction methodology are limitations., Conclusions: TCS withdrawal is likely a distinct clinical adverse effect of TCS misuse. Patients and providers should be aware of its clinical presentation and risk factors., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis is a common, chronic inflammatory dermatosis that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this final section, treatments for flare prevention and adjunctive and complementary therapies and approaches are reviewed. Suggestions on use are given based on available evidence., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The lack of core outcome sets for atopic eczema (AE) is a major obstacle for advancing evidence-based treatment. The global Harmonising Outcome Measures for Eczema (HOME) initiative has already defined clinical signs, symptoms, quality of life, and long-term control of flares as core outcome domains for AE trials. This article deals with the standardization of measurement instruments to assess clinical signs of AE. To resolve the current lack of standardization of the assessment of clinical signs of AE, we followed a structured process of systematic reviews and international consensus sessions to identify 1 core outcome measurement instrument for assessment of clinical signs in all future AE trials. Systematic reviews indicated that from 16 different instruments identified to assess clinical signs of AE, only the Eczema Area and Severity Index (EASI) and the objective Scoring Atopic Dermatitis (SCORAD) index were identified as extensively validated. The EASI has adequate validity, responsiveness, internal consistency, and intraobserver reliability. The objective SCORAD index has adequate validity, responsiveness, and interobserver reliability but unclear intraobserver reliability to measure clinical signs of AE. In an international consensus study, patients, physicians, nurses, methodologists, and pharmaceutical industry representatives agreed that the EASI is the preferred core instrument to measure clinical signs in all future AE trials. All stakeholders involved in designing, reporting, and using clinical trials on AE are asked to comply with this consensus to enable better evidence-based decision making, clearer scientific communication, and improved patient care., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (atopic eczema) is a chronic inflammatory skin disease that has reached epidemic proportions in children worldwide and is increasing in prevalence. Because of the significant socioeconomic effect of atopic dermatitis and its effect on the quality of life of children and families, there have been decades of research focused on disease prevention, with limited success. Recent advances in cutaneous biology suggest skin barrier defects might be key initiators of atopic dermatitis and possibly allergic sensitization., Objective: Our objective was to test whether skin barrier enhancement from birth represents a feasible strategy for reducing the incidence of atopic dermatitis in high-risk neonates., Methods: We performed a randomized controlled trial in the United States and United Kingdom of 124 neonates at high risk for atopic dermatitis. Parents in the intervention arm were instructed to apply full-body emollient therapy at least once per day starting within 3 weeks of birth. Parents in the control arm were asked to use no emollients. The primary feasibility outcome was the percentage of families willing to be randomized. The primary clinical outcome was the cumulative incidence of atopic dermatitis at 6 months, as assessed by a trained investigator., Results: Forty-two percent of eligible families agreed to be randomized into the trial. All participating families in the intervention arm found the intervention acceptable. A statistically significant protective effect was found with the use of daily emollient on the cumulative incidence of atopic dermatitis with a relative risk reduction of 50% (relative risk, 0.50; 95% CI, 0.28-0.9; P = .017). There were no emollient-related adverse events and no differences in adverse events between groups., Conclusion: The results of this trial demonstrate that emollient therapy from birth represents a feasible, safe, and effective approach for atopic dermatitis prevention. If confirmed in larger trials, emollient therapy from birth would be a simple and low-cost intervention that could reduce the global burden of allergic diseases., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is a common inflammatory skin disease with a global prevalence ranging from 3% to 20%. Patients with AD have an increased risk for complications after viral infection (eg, herpes simplex virus), and vaccination of patients with AD with live vaccinia virus is contraindicated because of a heightened risk of eczema vaccinatum, a rare but potentially lethal complication associated with smallpox vaccination., Objective: We sought to develop a better understanding of immunity to cutaneous viral infection in patients with AD., Methods: In a double-blind randomized study we investigated the safety and immunogenicity of live attenuated yellow fever virus (YFV) vaccination of nonatopic subjects and patients with AD after standard subcutaneous inoculation or transcutaneous vaccination administered with a bifurcated needle. Viremia, neutralizing antibody, and antiviral T-cell responses were analyzed for up to 30 days after vaccination., Results: YFV vaccination administered through either route was well tolerated. Subcutaneous vaccination resulted in higher seroconversion rates than transcutaneous vaccination but elicited similar antiviral antibody levels and T-cell responses in both the nonatopic and AD groups. After transcutaneous vaccination, both groups mounted similar neutralizing antibody responses, but patients with AD demonstrated lower antiviral T-cell responses by 30 days after vaccination. Among transcutaneously vaccinated subjects, a significant inverse correlation between baseline IgE levels and the magnitude of antiviral antibody and CD4(+) T-cell responses was observed., Conclusions: YFV vaccination of patients with AD through the transcutaneous route revealed that high baseline IgE levels provide a potential biomarker for predicting reduced virus-specific immune memory after transcutaneous infection with a live virus., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)