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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.)

Importance: Outcome measurement is an essential component of value-based health care and can aid patient care, quality improvement, and clinical effectiveness evidence generation. The Harmonising Outcome Measures for Eczema Clinical Practice initiative aims to identify a list of validated, feasible, outcome measurement instruments recommended to measure atopic dermatitis (AD) in the clinical practice setting. The clinical practice set is a list of instruments that clinicians can pick and choose from to suit their needs in the context of clinical care., Objective: To recommend instruments to measure clinical signs of AD in clinical practice., Evidence Review: Following the predefined roadmap, a mixed methods design was implemented and incorporated systematic reviews and qualitative consensus methods. Previous systematic reviews identified few clinical signs instruments with sufficient validation for recommendation. An updated systematic review evaluating the validity of clinical signs instruments informed an international meeting to reach consensus on recommended instruments to measure AD clinical signs in clinical practice. Consensus was defined as less than 30% disagreement. An in-person consensus exercise was held in Montreal, Canada, on October 16, 2022. The 34 attendees included patient and patient advocate research partners, health care professionals, researchers, methodologists, and industry representatives., Findings: The updated systematic review found that the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis, and objective Scoring Atopic Dermatitis were the only instruments that demonstrated sufficient performance in all assessed measurement properties. The modified EASI and Signs Global Assessment × Body Surface Area instruments were also recommended. The EASI, Validated Investigator Global Assessment, and Investigator's Global Assessment multiplied by or measured concurrently with a body surface area measure achieved consensus in criteria and were adopted., Conclusions and Relevance: This consensus statement by the Harmonising Outcome Measures for Eczema initiative suggests that when assessing and documenting clinical signs of AD, there are several valid and feasible instruments that can best fit a clinician's specific practice needs. These instruments should improve and standardize the documentation of signs severity, help determine the effect of treatment, facilitate the generation of clinical effectiveness evidence, and enhance the implementation of value-based health care.

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

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

Background: Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management., Objectives: The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE., Methods: In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg)., Results: Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0-5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores., Conclusions: Consistent with results seen in adults, adolescents, and older children (aged 6-11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population., Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B)., (© 2024. The Author(s).)

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

Background: Moderate-to-severe atopic dermatitis (AD) is inadequately controlled with current treatments for many patients. Abrocitinib is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of AD., Objective: The aim of the study was to evaluate patient-reported outcomes in a phase 2b study of abrocitinib in adults with moderate-to-severe AD inadequately controlled by topical therapy (NCT02780167)., Methods: Patients (N = 267) were randomly assigned 1:1:1:1:1 to 12-week, once-daily abrocitinib (200, 100, 30, 10 mg) or placebo. Patient-reported outcomes included pruritus numeric rating scale (average), Patient Global Assessment, Patient-Oriented Eczema Measure, Pruritus and Symptoms Assessment for AD, Dermatology Life Quality Index, and Hospital Anxiety and Depression Scale (HADS)., Results: Abrocitinib 200 or 100 mg resulted in significantly greater improvements from baseline versus placebo in peak pruritus numeric rating scale (by days 2 and 3, respectively), Patient-Oriented Eczema Measure, Pruritus and Symptoms Assessment for AD, Dermatology Life Quality Index, and HADS (200 mg only, by week 1 or 2), and proportions of the patients with Patient Global Assessment clear/almost clear with 2-point or greater improvement (by weeks 1 and 4, respectively) that continued through week 12 (except HADS)., Conclusions: Abrocitinib treatment resulted in rapid (2 days to 2 weeks) and persistent improvements in AD symptoms and impacts in moderate-to-severe disease., (Copyright © 2021 American Contact Dermatitis Society. All Rights Reserved.)

Background: Itch, the most bothersome symptom in atopic dermatitis, is largely mediated by pruritogenic cytokines via Janus kinase 1 signaling in cutaneous sensory neurons., Objectives: The aims of the study were to assess the magnitude and rapidity of itch relief with the Janus kinase 1 selective inhibitor abrocitinib and to evaluate the extent to which the effect of abrocitinib on itch relief is independent of overall disease improvement., Methods: Pooled data from 1 phase 2b (NCT02780167) and 2 phase 3 (NCT03349060, NCT03575871) double-blind, randomized, placebo-controlled monotherapy trials in moderate to severe atopic dermatitis (N = 942) were analyzed., Results: Abrocitinib produced significant and clinically meaningful itch relief versus placebo from week 2 through week 12 (end of treatment) that was associated with marked sleep and quality-of-life improvements. Mean percentage reductions in itch scores 24 hours after the first dose were greater for both abrocitinib doses (200 and 100 mg) versus placebo. Itch improvement occurred regardless of baseline itch severity, sex, race, body mass index, or Investigator Global Assessment response, suggesting that abrocitinib-associated itch relief is at least partially independent of overall disease improvement., Conclusions: Abrocitinib showed a rapid and profound antipruritic effect, partially independent of improvement in overall disease., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Contact Dermatitis Society.)

Background: Pain is a frequent symptom of atopic dermatitis (AD)., Objectives: The aims of the study were to evaluate the effects of dupilumab on pain/discomfort in AD and to determine whether pain correlates with other outcomes., Methods: This was a post hoc analysis of 5 randomized, placebo-controlled clinical trials in which adults with chronic AD received placebo or dupilumab 300 mg every 2 weeks or once weekly with and without topical corticosteroids. Proportions of patients with no pain/discomfort on this dimension of the 5-dimension EuroQoL (EQ-5D) at week 16 (all trials) and week 52 (CHRONOS) were compared between placebo and dupilumab. Correlations were evaluated between pain/discomfort and signs and symptoms of AD., Results: Among 2632 evaluated patients, 72.9% to 83.1% reported at least moderate pain/discomfort at baseline. Higher proportions treated with dupilumab reported no pain/discomfort at week 16 relative to placebo; risk differences ranged from 22.3% (95% confidence interval = 11.5%-33.1%) to 42.2% (95% confidence interval = 26.6%-57.8%, all P ≤ 0.0001), with similar effects observed at week 52. Correlations at baseline of pain/discomfort with signs and symptoms of AD were low to moderate., Conclusions: Pain/discomfort, present in a substantial proportion of patients with moderate-to-severe AD, was significantly reduced by dupilumab treatment. Given the low-to-moderate correlations with other AD symptoms at baseline, pain likely represents a distinct AD symptom.Trial Registration: ClinicalTrials.gov identifiers NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Contact Dermatitis Society.)

Background: Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, and tyrosine kinase 2. We aimed to assess the efficacy and safety of upadacitinib compared with placebo for the treatment of moderate-to-severe atopic dermatitis., Methods: Measure Up 1 and Measure Up 2 were replicate multicentre, randomised, double-blind, placebo-controlled, phase 3 trials; Measure Up 1 was done at 151 clinical centres in 24 countries across Europe, North and South America, Oceania, and the Asia-Pacific region; and Measure Up 2 was done at 154 clinical centres in 23 countries across Europe, North America, Oceania, and the Asia-Pacific region. Eligible patients were adolescents (aged 12-17 years) and adults (aged 18-75 years) with moderate-to-severe atopic dermatitis (≥10% of body surface area affected by atopic dermatitis, Eczema Area and Severity Index [EASI] score of ≥16, validated Investigator's Global Assessment for Atopic Dermatitis [vIGA-AD] score of ≥3, and Worst Pruritus Numerical Rating Scale score of ≥4). Patients were randomly assigned (1:1:1) using an interactive response technology system to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks, stratified by baseline disease severity, geographical region, and age. Coprimary endpoints were the proportion of patients who had achieved at least a 75% improvement in EASI score from baseline (EASI-75) and the proportion of patients who had achieved a vIGA-AD response (defined as a vIGA-AD score of 0 [clear] or 1 [almost clear] with ≥2 grades of reduction from baseline) at week 16. Efficacy was analysed in the intention-to-treat population and safety was analysed in all randomly assigned patients who received at least one dose of study drug. These trials are registered with ClinicalTrials.gov, NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2), and are both active but not recruiting., Findings: Between Aug 13, 2018, and Dec 23, 2019, 847 patients were randomly assigned to upadacitinib 15 mg (n=281), upadacitinib 30 mg (n=285), or placebo (n=281) in the Measure Up 1 study. Between July 27, 2018, and Jan 17, 2020, 836 patients were randomly assigned to upadacitinib 15 mg (n=276), upadacitinib 30 mg (n=282), or placebo (n=278) in the Measure Up 2 study. At week 16, the coprimary endpoints were met in both studies (all p<0·0001). The proportion of patients who had achieved EASI-75 at week 16 was significantly higher in the upadacitinib 15 mg (196 [70%] of 281 patients) and upadacitinib 30 mg (227 [80%] of 285 patients) groups than the placebo group (46 [16%] of 281 patients) in Measure Up 1 (adjusted difference in EASI-75 response rate vs placebo, 53·3% [95% CI 46·4-60·2] for the upadacitinib 15 mg group; 63·4% [57·1-69·8] for the upadacitinib 30 mg group) and Measure Up 2 (166 [60%] of 276 patients in the upadacitinib 15 mg group and 206 [73%] of 282 patients in the upadacitinib 30 mg group vs 37 [13%] of 278 patients in the placebo group; adjusted difference in EASI-75 response rate vs placebo, 46·9% [39·9-53·9] for the upadacitinib 15 mg group; 59·6% [53·1-66·2] for the upadacitinib 30 mg group). The proportion of patients who achieved a vIGA-AD response at week 16 was significantly higher in the upadacitinib 15 mg (135 [48%] patients) and upadacitinib 30 mg (177 [62%] patients) groups than the placebo group (24 [8%] patients) in Measure Up 1 (adjusted difference in vIGA-AD response rate vs placebo, 39·8% [33·2-46·4] for the upadacitinib 15 mg group; 53·6% [47·2-60·0] for the upadacitinib 30 mg group) and Measure Up 2 (107 [39%] patients in the upadacitinib 15 mg group and 147 [52%] patients in the upadacitinib 30 mg group vs 13 [5%] patients in the placebo group; adjusted difference in vIGA-AD response rate vs placebo, 34·0% [27·8-40·2] for the upadacitinib 15 mg group; 47·4% [41·0-53·7] for the upadacitinib 30 mg group). Both upadacitinib doses were well tolerated. The incidence of serious adverse events and adverse events leading to study drug discontinuation were similar among groups. The most frequently reported treatment-emergent adverse events were acne (19 [7%] of 281 patients in the upadacitinib 15 mg group, 49 [17%] of 285 patients in the upadacitinib 30 mg group, and six [2%] of 281 patients in the placebo group in Measure Up 1; 35 [13%] of 276 patients in the upadacitinib 15 mg group, 41 [15%] of 282 patients in the upadacitinib 30 mg group, and six [2%] of 278 patients in the placebo group in Measure Up 2), upper respiratory tract infection (25 [9%] patients, 38 [13%] patients, and 20 [7%] patients; 19 [7%] patients, 17 [16%] patients, and 12 [4%] patients), nasopharyngitis (22 [8%] patients, 33 [12%] patients, and 16 [6%] patients; 16 [6%] patients, 18 [6%] patients, and 13 [5%] patients), headache (14 [5%] patients, 19 [7%] patients, and 12 [4%] patients; 18 [7%] patients, 20 [7%] patients, and 11 [4%] patients), elevation in creatine phosphokinase levels (16 [6%] patients, 16 [6%] patients, and seven [3%] patients; nine [3%] patients, 12 [4%] patients, and five [2%] patients), and atopic dermatitis (nine [3%] patients, four [1%] patients, and 26 [9%] patients; eight [3%] patients, four [1%] patients, and 26 [9%] patients)., Interpretation: Monotherapy with upadacitinib might be an effective treatment option and had a positive benefit-risk profile in adolescents and adults with moderate-to-severe atopic dermatitis., Funding: AbbVie., Competing Interests: Declaration of interests EG-Y is employed by Mount Sinai and is a researcher or consultant for AbbVie, Anacor, AnaptysBio, Asana Biosciences, Botanix, Celgene, DBV, Dermira, Dr Reddy's Laboratory (Promius), DS Biopharma, Escalier Biosciences, Galderma, Glenmark, Innovaderm, Janssen, Kyowa Kirin, LEO Pharma, Lilly, AstraZeneca, Mitsubishi Tanabe Pharma, Novan, Novartis, Pfizer, Ralexar, Regeneron, Sanofi, GlaxoSmithKline, UCB, and Vitae Pharmaceuticals. HDT, ALP, BC, YG, XH, ML, YY, JL, ART, and ADC are full-time employees of AbbVie, and might hold AbbVie stock or stock options. ELS reports grants, personal fees, and non-financial support from Lilly; grants and personal fees from Anacor, Bausch Health (Valeant), GlaxoSmithKline, LEO Pharma, Lilly, Pfizer, Regeneron, and Sanofi Genzyme; personal fees from AbbVie, Celgene, Dermira, Galderma, Genentech, LEO Pharma, and Menlo Therapeutics; and grants from MedImmune, Novartis, Roivant, Tioga Pharmaceuticals, and Vanda. KAP is an adviser, speaker, consultant, and steering committee member or researcher for AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, Astellas, AstraZeneca, Bausch Health (Valeant), Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite, Celgene, Coherus, Dermira, Dow, Forward Pharma, Galderma, Genentech, Gilead, GlaxoSmithKline, InflaRx, Janssen, Kyowa Kirin, LEO Pharma, Lilly, MedImmune, Meiji Seika Pharma, Merck, Mitsubishi Tanabe Pharma, Moberg Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, and UCB. AB has served as a scientific adviser or clinical study investigator for AbbVie, Almirall, Arena Pharmaceuticals, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Forté Pharma, Galderma, Incyte, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, RAPT Therapeutics, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB; and is a paid speaker for AbbVie. DT is an advisor, speaker, or consultant for AbbVie, Almirall, Amgen, Asana Biosciences, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, DS Biopharma, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Sandoz, Sanofi Genzyme, and UCB; and is also involved in research for AbbVie, Celgene, LEO Pharma, and Novartis. C-YC is an investigator for AbbVie, Dermira, Lilly, Novartis, Oneness Biotech, Pfizer, Regeneron, Roche, and Sanofi; a consultant for AbbVie, Lilly, Novartis, Pfizer, Roche, and Sanofi; a speaker for AbbVie, Lilly, Mylan, Novartis, Pfizer, Roche, and Sanofi; and an advisory board member for Mylan, Pfizer, Roche, and Sanofi. HCH is a researcher, consultant, or advisor for AbbVie, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol-Meyers Squibb, Celgene, Dermira, Dermavant, DS Biopharma, Galderma, GlaxoSmithKline, Janssen, LEO Pharma, Lilly, MedImmune, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, and UCB. NK has received honoraria as a speaker or consultant for AbbVie, Janssen, LEO Pharma, Lilly, Maruho, Mitsubishi Tanabe Pharma, Sanofi, and Taiho Pharmaceutical, and has received grants as an investigator from AbbVie, Kyowa Kirin, LEO Pharma, Lilly, Maruho, Mitsubishi Tanabe Pharma, and Sanofi. ASP has served as an investigator for AbbVie, Anaptysbio, Incyte, Janssen, LEO Pharma, Lilly, Lenus, Novartis, Regeneron, and UCB, and received honorarium for consultancy from AbbVie, Abeona, Almirall, Asana Biosciences, Boehringer Ingelheim, Bridgebio, Dermavant, Dermira, Exicure, Forte Pharma, Galderma, Incyte, InMed, Janssen, LEO Pharma, Lilly, LifeMax, Novartis, Pfizer, RAPT Therapeutics, Regeneron, Sanofi Genzyme, Sol-Gel, and UCB. ADI has received honorarium for consultancy from AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai, Dermavant, Genentech, LEO Pharma, Lilly, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, and UCB., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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

Atopic dermatitis (AD) is a pruritic or painful dermatologic disease characterized by xerosis and eczema lesions. The symptoms/signs of AD can significantly impact patients' health-related quality of life (HRQoL). This study aimed to qualitatively explore the adult and adolescent experience of AD. A targeted literature review and qualitative concept elicitation interviews with clinicians (n = 5), adult AD patients (n = 28), and adolescent AD patients (n = 20) were conducted to elicit AD signs/symptoms and HRQoL impacts experienced. Verbatim transcripts were analyzed using thematic analysis. Twenty-nine symptoms/signs of AD were reported, including pruritus, pain, erythema, and xerosis. Atopic dermatitis symptoms/signs were reported to substantially impact HRQoL. Scratching was reported to influence the experience of symptoms and HRQoL impacts. Four proximal impacts (including discomfort and sleep disturbance) were reported. Ten domains of distal impact were reported, including impacts on psychological and social functioning and activities of daily living. A conceptual model was developed to summarize these findings. This study highlights the range of symptoms and HRQoL impacts experienced by adults and adolescents with AD. To our knowledge, this study was first to explore the lived experience of AD in both adult and adolescent patients, providing valuable insight into the relatively unexplored adolescent experience of AD.

Background: Atopic dermatitis (AD) is associated with skin lesions, multiple symptoms, and effect of quality of life, all of which factor into disease severity. Self-reported global AD severity may be a valid severity assessment for epidemiologic research., Objective: To validate self-reported global AD severity in a representative cohort of adults with AD., Methods: Preliminary probing-cognitive interviews were performed (n = 8). Next, a cross-sectional US population-based survey study of adults with AD was performed. AD was diagnosed using an adap/tation of the UK Working Party criteria (n = 602). AD severity was assessed using self-reported global AD severity (mild, moderate, severe), Patient-Oriented Scoring AD (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), Numeric Rating Scale (NRS)-itch, NRS-sleep, NRS-pain, and Hospital Anxiety and Depression Scale (HADS)., Results: Self-reported global AD severity had good content validity. Self-reported global AD severity had strong correlations with PO-SCORAD (Spearman correlation ρ = 0.61) and objective PO-SCORAD (ρ = 0.61); moderate correlations with POEM (ρ = 0.54), NRS-itch (ρ = 0.44), NRS-pain (ρ = 0.46), and HADS (ρ = 0.41); and weak correlation with NRS-sleep (ρ = .32) (P < .001 for all). Consistent and significant correlations were observed in stratified analyses by age, sex, race/ethnicity, and level of education. There were stepwise increases of PO-SCORAD, NRS-itch, NRS-sleep, NRS-pain, POEM, and HADS with increasing self-reported global AD severity (Kruskal-Wallis test, P < .01). There was weak-moderate concordance between self-reported AD severity and established severity strata for PO-SCORAD (ρ = 0.44), NRS-itch (ρ = 0.30), and POEM (ρ = 0.43). Rather, self-reported global AD severity was best predicted by a combination of PO-SCORAD, POEM, NRS-itch, NRS-pain, and HADS. No differential item reporting was found by age, sex, or race/ethnicity., Conclusion: Self-reported AD severity simultaneously assesses multiple AD constructs and appears to be sufficiently valid for assessing AD severity in clinical and epidemiologic studies., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patient-Oriented Eczema Measure (POEM) is the preferred patient-reported outcome (PRO) for assessing symptoms of atopic dermatitis (AD). Dermatology Life Quality Index (DLQI) is commonly used to assess the burden of skin disease. Previous severity strata were developed for POEM and DLQI in clinical cohorts, which may be biased toward more severe disease. Severity strata were not previously examined in population-based cohorts. Patient-Oriented Scoring AD (PO-SCORAD) is another commonly used PRO for assessing AD symptoms; however, severity strata are not established., Objective: We sought to confirm previously developed strata for POEM and DLQI, and to develop strata for the PO-SCORAD in a population-based cohort of adults with AD., Methods: A cross-sectional, population-based study of 8,217 adults was performed using a structured questionnaire. A diagnosis of AD was determined using modified UK Diagnostic Criteria for AD (n = 602). AD severity was assessed using self-reported global AD severity (anchoring question), POEM, PO-SCORAD, and DLQI. Strata were selected using an anchoring approach based on patient-reported disease severity., Results: We confirmed the existing strata for DLQI (mild = 0-5, moderate = 6-10, severe = 11-30) (kappa = 0.446). However, the preferred strata for POEM was mild = 0-7, moderate = 8-19, and severe = 20-28 (kappa = 0.409) and PO-SCORAD was mild = 1-27, moderate = 28-56, severe = 57-104 (kappa = 0.444)., Conclusion: Existing strata for DLQI performed well in a population-based cohort of adult AD. The optimal severity strata for the POEM in our AD population varies slightly from those previously published for AD. This may suggest that different strata may be optimal in different study settings and cohorts. Finally, we proposed new strata for PO-SCORAD in adult AD., (Copyright © 2018 The Authors. 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: Little is known about the predictors of eczema severity in the US population., Objectives: We sought to determine the distribution and associations of childhood eczema severity in the United States., Methods: We analyzed the data from the 2007 National Survey of Children's Health, a prospective questionnaire-based study of a nationally representative sample of 91,642 children (range, 0-17 years)., Results: The prevalence of childhood eczema was 12.97% (95% confidence interval [95% CI], 12.42-13.53); 67.0% (95% CI, 64.8-69.2) had mild disease, 26.0% (95% CI, 23.9-28.1) had moderate disease, and 7.0% (95% CI, 5.8-8.3) had severe disease. There was significant statewide variation of the distribution of eczema severity (Rao-Scott χ, P = 0.004), with highest rates of severe disease in Mid-Atlantic and Midwestern states. In univariate models, eczema severity was increased with older age, African American and Hispanic race/ethnicity, lower household income, oldest child in the family, home with a single mother, lower paternal/maternal education level, maternal general health, maternal/paternal emotional health, dilapidated housing, and garbage on the streets. In multivariate survey logistic regression models using stepwise and backward selection, moderate-to-severe eczema was associated with older age, lower household income, and fair or poor maternal health but inversely associated with birthplace outside the United States., Conclusions: These data indicate that environmental and/or lifestyle factors play an important role in eczema severity.

BackgroundThe validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) is a standardized severity assessment for use in clinical trials and registries for atopic dermatitis (AD).ObjectivesTo investigate the reliability, validity, responsiveness and within-patient meaningful change of the vIGA-AD.MethodsData were analysed from adult patients with moderate-to-severe AD in the BREEZE-AD1 (N = 624 patients; NCT03334396), BREEZE-AD2 (N = 615; NCT03334422) and BREEZE-AD5 (N = 440; NCT03435081) phase III baricitinib clinical studies.ResultsAcross studies, test-retest reliability for stable patients showed moderate-to-good agreement [range of Kappa values for Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD), 0·516-0·639; for Eczema Area and Severity Index (EASI), 0·658-0·778]. Moderate-to-large correlations between vIGA-AD and EASI or body surface area (range at baseline, 0·497-0·736; Week 16, 0·716-0·893) supported convergent validity. Known-groups validity was demonstrated vs. EASI and PGI-S-AD (vIGA-AD for severe vs. moderate EASI categories at baseline, P

BackgroundPatients with moderate-to-severe atopic dermatitis (AD) have increased infection risk, including skin infections and systemic infections. Immunomodulators (e.g., anti-tumor necrosis factors, anti-interleukin [anti-IL]-23, anti-IL-17, Janus kinase inhibitors) increase risk of infections. Dupilumab (a monoclonal antibody blocking the shared receptor component for IL-4 and IL-13) is approved for inadequately controlled moderate-to-severe AD and for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma.ObjectiveThe aim was to determine the impact of dupilumab on infection rates in patients with moderate-to-severe AD.MethodsThis analysis pooled data from seven randomized, placebo-controlled dupilumab trials in adults with moderate-to-severe AD. Exposure-adjusted analyses assessed infection rates.ResultsOf 2932 patients, 1091 received placebo, 1095 dupilumab 300 mg weekly, and 746 dupilumab 300 mg every 2 weeks. Treatment groups had similar infection rates overall per 100 patient-years (placebo, 155; dupilumab weekly, 150; dupilumab every 2 weeks, 156; dupilumab combined, 152), and similar non-skin infection rates. Serious/severe infections were reduced with dupilumab (risk ratio 0.43; p

Atopic dermatitis (AD) 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 the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed.

Background and Objective: Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) is a difficult endpoint to achieve after short-term treatment of chronic moderate-to-severe atopic dermatitis, and does not fully reflect clinically meaningful changes in other parameters. We assessed the impact of tralokinumab versus placebo on other clinically meaningful parameters in patients not achieving IGA 0/1 at week 16 using pooled data from two monotherapy phase III trials, ECZTRA 1 and 2. Methods: This post hoc analysis included patients (n = 1328) from ECZTRA 1 and 2 who did not achieve the co-primary endpoint, IGA 0/1 at week 16 without rescue medication. Endpoints evaluating atopic dermatitis extent and severity included proportions of patients achieving IGA 0/1, 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI-50/75/90); endpoints evaluating patient-reported outcomes included a ≥ 3-point improvement in worst daily pruritus Numerical Rating Scale (NRS), a ≥ 3-point improvement in eczema-related sleep interference (sleep) NRS, a ≥ 4-point improvement in Dermatology Life Quality Index (DLQI), and DLQI ≤ 5. Specifically, clinically meaningful responses were defined as EASI-50, a ≥ 3-point improvement in itch NRS, or a ≥ 4-point improvement in DLQI at week 16. Results: Among ECZTRA 1 and 2 patients who did not achieve IGA 0/1 at week 16 without rescue medication, a significantly greater proportion of patients receiving tralokinumab versus placebo achieved EASI-50 (33.0% vs 13.0%), a ≥ 3-point improvement in itch NRS (22.6% vs 9.4%), or a ≥ 4-point improvement in DLQI (41.2% vs 24.5%) at week 16. In addition, compared with placebo, a numerically greater proportion of tralokinumab-treated patients achieved all three measures of clinically meaningful response (30% vs 18%) or a clinically meaningful change in at least one outcome (48.8% vs 28.5%). Significantly greater proportions of patients receiving tralokinumab versus placebo achieved additional clinician-reported and patient-reported outcomes, such as EASI-75 (13.5% vs 4.1%), EASI-90 (3.5% vs 1.1%), DLQI ≤ 5 (22.5% vs 12.5%), and a ≥ 3-point improvement in sleep NRS (24.5% vs 11.5%). Conclusions: Tralokinumab provided clinically meaningful responses in patients with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Using multiple validated outcome measures of both efficacy and quality of life, alongside IGA scores, can better characterize tralokinumab treatment responses in patients with moderate-to-severe atopic dermatitis. [Video abstract available] Clinical Trial Registration: NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019. 6QcTdZHHiWG8xHjHtHEVo6 Video abstract: Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1 (MP4 362818 KB) [ABSTRACT FROM AUTHOR]

Background: Two phase III trials, ECZTRA 1 and 2, confirmed the efficacy and safety of tralokinumab versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To further explore the long-term efficacy of tralokinumab for AD, a pooled analysis of these trials was conducted. Methods: ECZTRA 1 and 2 patients (n = 1596 total) were randomized to tralokinumab 300 mg or placebo every 2 weeks (q2w) over 16 weeks. Patients achieving Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 16, were re-randomized to tralokinumab q2w, every 4 weeks (q4w), or placebo (tralokinumab withdrawal) for another 36 weeks. Patients not achieving the response criteria at Week 16 received open-label tralokinumab q2w plus optional topical corticosteroids (TCS). A pooled, prespecified analysis assessed the proportions of Week 16 responders that maintained IGA 0/1 and/or EASI-75 at Week 52. Pooled data from all patients initiated with tralokinumab, regardless of the response at Week 16 or dosing regimen received thereafter, were analyzed post hoc. Results: In patients who achieved the primary endpoints at Week 16, IGA 0/1 responses were maintained at Week 52 without rescue treatment (including TCS) by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, or placebo (tralokinumab withdrawal), respectively, while EASI-75 responses were maintained by 57.3%, 50.4%, and 26.4%, respectively (prespecified analysis). In a post hoc analysis of all patients initiated with tralokinumab, response rates improved over time with continued tralokinumab treatment beyond Week 16 to Week 52 for EASI-50 (63.1–82.7%), EASI-75 (37.6–61.8%), EASI-90 (20.4–37.3%), and IGA 0/1 (23.0–36.2%). Conclusions: Tralokinumab treatment provides progressive and sustained improvement over 1 year in the extent and severity of AD in patients with moderate-to-severe AD. Clinical Trial Registration: NCT03131648 (ECZTRA 1); study start date: 30 May 2017; primary completion date: 7 August 2018; study completion date: 10 October 2019. NCT03160885 (ECZTRA 2); study start date: 12 June 2017; primary completion date: 4 September 2019; study completion date: 14 August 2019. Infographic: Plain Language Summary: Atopic dermatitis (AD) is a chronic inflammatory disease characterized by excessively dry and itchy skin, resulting in a considerable burden of disease. Patients with AD often require long-term treatment. Tralokinumab is an injectable antibody treatment that targets a protein called interleukin-13, which substantially contributes to the signs and symptoms of AD. In the ECZTRA 1 and 2 phase III clinical trials, funded by LEO Pharma A/S, adults with moderate-to-severe AD treated with tralokinumab every other week for 16 weeks showed significant improvement in disease extent and severity compared with patients receiving placebo. To further explore the long-term efficacy of tralokinumab for AD, we performed a new analysis combining the almost 1600 patients of ECZTRA 1 and 2. A large proportion of patients treated with tralokinumab who achieved clear or almost clear skin at Week 16 were able to maintain clear or almost clear skin at Week 52 with less frequent dosing (every 4 weeks). Additionally, combining all patients treated with tralokinumab, regardless of Week 16 response or dose frequency thereafter, showed that most patients achieved a significant reduction in disease extent and severity at Week 52. These results demonstrate that many tralokinumab-treated patients continue to improve beyond Week 16, and highlight that efficacy results at Week 16 may not be representative of the outcome of longer-term tralokinumab treatment. These findings may help health care providers better advise patients regarding when to modify treatment with tralokinumab. [ABSTRACT FROM AUTHOR]

Background: Traditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200 mg and 100 mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch response (with abrocitinib 200 mg) than dupilumab at week 2. Objective: This study assessed the efficacy and safety of abrocitinib and dupilumab in a subset of patients with severe and/or difficult-to-treat AD in a post hoc analysis of the JADE COMPARE trial. Methods: Adults with moderate-to-severe AD received once-daily oral abrocitinib 200 mg or 100 mg, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo with concomitant medicated topical therapy. Severe and/or difficult-to-treat AD subgroups were classified by baseline characteristics [Investigator's Global Assessment (IGA) 4, Eczema Area and Severity Index (EASI) > 21, failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids), percentage of body surface area (%BSA) > 50, upper quartiles of EASI (EASI > 38) and %BSA (%BSA > 65), and combined subgroup of IGA 4, EASI > 21, and %BSA > 50, and failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids)]. Assessments included IGA score of 0 (clear) or 1 (almost clear) and a ≥ 2-point improvement from baseline, ≥ 75% and ≥ 90% improvement from baseline in EASI (EASI-75 and EASI-90), ≥ 4-point improvement from baseline in Peak Pruritus-Numerical Rating Scale (PP-NRS4), time to PP-NRS4, least squares mean (LSM) change from baseline in 14-day PP-NRS (days 2–15), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI) up to week 16. Results: The proportion of patients achieving IGA 0/1, EASI-75, and EASI-90 responses was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.05) across all subgroups with severe and/or difficult-to-treat AD. Across most subgroups, PP-NRS4 response was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.01); the time to achieve this response was shorter with abrocitinib 200 mg (range 4.5–6.0 days) than abrocitinib 100 mg (range 5.0–17.0 days), dupilumab (range 8.0–11.0 days), and placebo (range 3.0–11.5 days). LSM change from baseline in POEM and DLQI was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.001) across all subgroups. Clinically meaningful differences were observed between abrocitinib and dupilumab for most evaluated endpoints across several subgroups, including in patients who failed or were intolerant to prior systemic therapy. Conclusions: Abrocitinib provided rapid and substantially greater improvements in skin clearance and quality of life compared with placebo and dupilumab in subgroups of patients with severe and/or difficult-to-treat AD. These findings support the use of abrocitinib for severe and/or difficult-to-treat AD. Trial registration: ClinicalTrials.gov, NCT03720470. Plain Language Summary: Atopic dermatitis (AD), also known as atopic eczema, is a skin disease that causes itchy and red skin patches. People can be diagnosed with severe and/or difficult-to-treat AD if their signs and symptoms of AD are extremely severe and their AD cannot be adequately treated by common medicines. Abrocitinib is a treatment that has been shown in clinical trials to improve the symptoms of AD. We analyzed data from the JADE COMPARE study, which included 837 people who were treated with abrocitinib, dupilumab (another treatment for AD), or placebo. Many of these people had severe symptoms when they entered the study. Some had AD signs and symptoms that did not improve after they took common medicines for AD. We studied how well abrocitinib worked in these people with severe and/or difficult-to-treat AD. We found that these people achieved clear skin and itch relief at week 16 after treatment with abrocitinib 200 mg compared with placebo (no drug control). Additionally, they achieved significant relief from itch faster with abrocitinib 200 mg compared with abrocitinib 100 mg, dupilumab, or placebo. People reported less severe AD and better quality of life after treatment with abrocitinib compared with placebo. Together, the findings of our study provide important evidence for healthcare providers as they determine a treatment plan for people with severe and/or difficult-to-treat AD. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral Janus kinase 1 inhibitor, provided significant itch relief by week 2 in patients with moderate-to-severe atopic dermatitis (AD) in the phase III JADE COMPARE trial. Objectives: This post-hoc analysis of JADE COMPARE aimed to further characterize itch response and determined whether early itch relief could predict subsequent improvements in AD severity. Methods: JADE COMPARE was a randomized, double-blind, double-dummy, placebo-controlled trial. Adult patients (aged ≥ 18 years) with moderate-to-severe AD were randomly assigned to receive oral abrocitinib 200 mg or 100 mg once daily, subcutaneous dupilumab 300 mg every other week (after a 600-mg loading dose), or placebo, plus medicated topical therapy for 16 weeks. Assessments were ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) from days 2 to 15, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA) response, and Dermatology Life Quality Index (DLQI) scores at week 12. Association between week 2 PP-NRS4 and efficacy at week 12 was evaluated by chi-squared tests. The predictive value of early response for later efficacy was assessed by area under the receiver operating characteristic curve. Results: As early as day 4 after treatment, a significantly greater proportion of patients achieved PP-NRS4 response with abrocitinib 200 mg (18.6%) versus dupilumab (5.6%; p < 0.001) and placebo (6.0%; p < 0.003). A similar trend was observed with abrocitinib at the 100-mg dose, with significantly greater PP-NRS4 response rates versus placebo as early as day 9. With both doses of abrocitinib, week 12 IGA 0/1, EASI-75, EASI-90, and DLQI 0/1 response rates were greater in week 2 PP-NRS4 responders than nonresponders; no differences were observed between week 2 PP-NRS4 responders and nonresponders in the dupilumab and placebo groups. Early improvement in PP-NRS at week 2 was associated with skin clearance at week 12 in abrocitinib-treated patients. Conclusions: Abrocitinib resulted in rapid relief from itch in patients with moderate-to-severe AD, with significant improvement in itch as early as day 4 after treatment with abrocitinib 200 mg compared with dupilumab and placebo. Abrocitinib-induced itch relief by week 2 was associated with subsequent improvements at week 12. [Video abstract available.] Trial registration: ClinicalTrials.gov identifier: NCT03720470. 2fQ_82bhGurT9XTD9WAh-8 Early itch response with abrocitinib is associated with later efficacy outcomes in patients withmoderate-to-severe atopic dermatitis: subgroup analysis of the randomized phase III JADE COMPARE trial (MP4 335,375kb) Plain Language Summary: An investigation into whether quick relief from itch with abrocitinib, a new medicine for atopic dermatitis, leads to later improvements in skin rash Atopic dermatitis (AD), also called atopic eczema, is a skin disease that affects people throughout their lives. About 10% of adults worldwide have AD. Itch is the most bothersome symptom reported by people with AD and scratching this itch can damage the skin, resulting in painful sores. It is unknown if relief from itch can influence other symptoms of AD. We analyzed data from the JADE COMPARE study, which included 837 people who received treatment with abrocitinib, dupilumab or placebo. We studied how fast itch relief occurred after people received these treatments. We also wanted to study if rapid itch relief was associated with improvement in other signs of AD later on with continued treatment. We found that as early as 4 days after treatment, abrocitinib 200 mg provided significant relief from itch compared with dupilumab or placebo. People who had rapid itch relief within 2 weeks of treatment with abrocitinib were more likely to have clear or almost clear skin and improved quality of life after 12 weeks of continued treatment with abrocitinib. Rapid itch relief did not appear to increase the likelihood of clear skin at week 12 in people who received dupilumab. Larger studies are needed to confirm this result. This study provides important evidence for physicians as they analyze itch relief and determine treatment options for people with AD. [ABSTRACT FROM AUTHOR]

Background: Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis.Methods: This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434.Findings: Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation.Interpretation: Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults.Funding: Sanofi and Regeneron Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: For adolescent patients (aged ≥ 12 to < 18 years) with uncontrolled moderate-to-severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile. However, long-term data on the approved dose regimens of dupilumab in adolescents with AD are lacking. Objectives: This open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate-to-severe AD who had participated in dupilumab parent trials. Methods: Patients enrolled under the original study protocol received subcutaneous dupilumab according to a weight-based regimen (2 or 4 mg/kg every week). Following protocol amendment, patients were switched to subcutaneous dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, and newly enrolled patients were started on dupilumab 300 mg q4w. Patients with an inadequate clinical response (Investigator's Global Assessment [IGA] score of 0/1 was not reached) to the q4w regimen could be uptitrated to the approved dupilumab dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively). Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required. Results: Data for 294 patients (mean age 14.7 years) were analyzed, 102 (34.7%) of whom had completed the 52-week visit at the database lock. The dupilumab long-term safety profile was comparable to that seen in adults and consistent with the known safety profile. Most treatment-emergent adverse events were mild/moderate. By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in Eczema Area and Severity Index (EASI). Most (70.9%) patients required uptitration to the approved dupilumab dose regimen. The proportions of uptitrated patients with an IGA score of 0/1 or 75% improvement in EASI increased over time, reaching 35.7% and 51.9%, respectively, 48 weeks after the first uptitration visit. By week 52, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication; 56.7% relapsed and were subsequently re-initiated on treatment, with a mean time to re-initiation of 17.5 (± standard deviation 17.3) weeks. Conclusions: Consistent with results seen with short-term treatment, long-term treatment with dupilumab showed an acceptable safety profile while providing incremental clinical benefit with continued treatment over time. The high proportion of patients who needed uptitration because of inadequate response to q4w dosing supports the q2w dose regimen as optimal for this age group. Finally, the majority of patients who stopped medication after having clear/almost clear skin sustained over 12 weeks experienced disease recurrence, suggesting the need for continued dupilumab dosing to maintain efficacy. Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454, NCT02407756, NCT03054428, and NCT03050151. Infographic: EYru5bYjcUouUcQrkiC3DM Video abstract: What is the long-term safety and efficacy profile in adolescents with moderate-to-severe atopic dermatitis treated with the approved dupilumab dose regimen? (MP4 40,966 KB) Plain Language Summary: Atopic dermatitis, or eczema, is a common chronic skin disease that can cause intense and persistent itching and rashes. Atopic dermatitis remains a problem for many adolescent patients, even if they use a number of different treatments. Dupilumab is a newer treatment for atopic dermatitis. In short-term clinical studies, dupilumab improved the disease with acceptable safety. In this study, adolescents with moderate-to-severe atopic dermatitis who had completed one of the short-term studies continued dupilumab treatment for 1 year. The patients started treatment with dupilumab once every 4 weeks. But if their atopic dermatitis did not improve sufficiently, they were given dupilumab every 2 weeks. Through a year of treatment, there were no unexpected side effects. The side effects that did occur were mild or moderate in severity and in most cases did not lead to interruption of treatment. Almost half of the patients achieved skin that was clear or almost clear of atopic dermatitis during the study. But their atopic dermatitis often returned if they stopped being treated, and about half of them needed to start treatment again. Most patients needed to be treated every 2 weeks. The positive effects of dupilumab generally increased the longer patients were treated. [ABSTRACT FROM AUTHOR]

The recent advent of numerous clinical trials for the treatment of moderate-to-severe atopic dermatitis has led to new and emerging therapeutic options for this chronic inflammatory skin disease. With this rapid development has come a lack of consistency in study designs, trial conduct, and statistical analyses. Healthcare providers are challenged to interpret how variations in study parameters may influence clinical trial results. Based on literature review and our experience as clinical trialists, we compiled a list of 22 key study parameters of contemporary clinical trials in moderate-to-severe atopic dermatitis and ranked the top study parameters that may have a significant effect on efficacy results. The top parameters included study comparators, rules for rescue treatment, washout periods for topical and systemic treatments, inclusion criteria such as disease severity by Eczema Area and Severity Index and/or Investigator Global Assessment scores, and the duration of the screening period. We describe considerations for these key parameters, with a focus on between-parameter interactions and effect on efficacy results. This may serve to inform the interpretation of atopic dermatitis clinical trials and raise the profile of the need to harmonize the clinical trial design. Plain Language Summary: Atopic dermatitis (AD) is a skin disease characterized by red, itchy skin that is highly burdensome for patients. Patients with moderate-to-severe disease have large, inflamed skin areas with frequent itching. Recently, the number of clinical trials for drugs that treat moderate-to-severe AD has rapidly increased, with differences in how these trials are designed. There is a need for healthcare providers examining results from different clinical trials to understand how trial design factors might influence study outcomes. In this article, we identify key trial design factors that impact study outcomes, detail how these factors can impact clinical trial results, and explore how these factors interact with one another to affect study outcomes. The five most important design factors, as determined via author surveys, were study comparators (a placebo and/or another drug to which the drug being studied is compared); the rules for the use of rescue treatment (a form of treatment given if an enrolled participant has uncontrolled AD symptoms); washout periods (the time before the trial when previous treatments are stopped to allow them to be cleared from a patient's system); inclusion criteria (that determine which participants are included); and the length of the screening period (the time when patients are assessed to determine if they qualify for participation). By understanding how these key trial design factors impact on study outcomes, healthcare providers may be equipped to better interpret different AD clinical trials. This work also emphasizes the value of harmonizing the AD clinical trial design. [ABSTRACT FROM AUTHOR]

Background: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. Objective: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. Methods: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. Results: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. Conclusion: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. Trial Registries: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis imparts a substantial patient burden, including itch, sleep disturbance, and decreased health-related quality of life. Objective: This analysis evaluated changes in patient-reported outcomes of disease-specific signs/symptoms and health-related quality of life in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with once-daily oral abrocitinib 200-mg or 100-mg monotherapy. Methods: Pooled data from one phase IIb (NCT02780167) and two phase III (NCT03349060, JADE MONO-1; NCT03575871, JADE MONO-2) monotherapy trials in adult and adolescent patients with moderate-to-severe atopic dermatitis were analyzed. Patient-reported outcome assessments included: global severity, itch, and multi-item measures that assess other signs and symptoms of atopic dermatitis. Additional patient-reported outcome assessments measured depression, anxiety, fatigue, disease-specific and general health-related quality of life, and work and general productivity among employed patients. Results: Overall, 942 patients were included in this analysis. Improvements were observed from the first post-baseline assessment to week 12 across all patient-reported outcomes, including Patient Global Assessment (PtGA) score of 0/1 (35.5%, 19.8%, and 5.9% for 200 mg, 100 mg, and placebo, respectively), ≥ 4-point improvement in Night Time Itch Scale (NTIS; 57.0%, 42.7%, and 12.7%), change from baseline in Patient-Oriented Eczema Measure (POEM) score (− 11.4, − 8.2, and − 3.4), 1-point improvement in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD; 75.2%, 65.1%, and 33.5%), Hospital Anxiety and Depression Scales (HADS) anxiety (− 2.0, − 1.7, and − 1.0) and depression (− 1.7, − 1.3, and − 0.1). Conclusions: Abrocitinib monotherapy improved disease-specific signs/symptoms and health-related quality of life across multiple domains as reported by adult and adolescent patients with moderate-to-severe atopic dermatitis, complementing clinician-reported efficacy and safety outcomes. Clinical Trial Registration: NCT02780167 (registered 23 May, 2016), NCT03349060 (registered 21 November, 2017), NCT03575871 (registered 3 July, 2018). [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis.Methods: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060.Findings: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported.Interpretation: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis.Funding: Pfizer. [ABSTRACT FROM AUTHOR]

Objectives: The Atopic Dermatitis Control Tool (ADCT) was designed to evaluate patient-perceived AD control and facilitate patient-physician discussion on long-term disease control.Methods: The study was performed in adult patients with AD. Development of the ADCT followed US Food and Drug Administration (FDA) guidelines on patient-reported outcome measures (PROMs). Qualitative research, including targeted literature review, interviews with clinical experts, and combined concept elicitation/cognitive debriefing with patients with AD, was conducted to provide a list of comprehensive concepts capturing AD control per physician and patient perspectives. Quantitative methods assessed psychometric properties of the instrument and defined the threshold for AD control.Results: The resulting pilot six-item ADCT, reflecting key concepts related to AD control, had 7-day recall and assessed symptoms and impacts on patients' everyday lives by severity and/or frequency. The ADCT showed good content validity (well understood by adult patients with AD), and quick completion time (<2 min). Psychometric analysis indicated no floor/ceiling effects for response distributions, particularly strong (r ≥ 0.80) inter-item correlations for the six ADCT items, robust construct validity (r > 0.50), and item-level discriminating ability (p < .03); this supported the derivation of a total score based on responses to all items. ADCT total score showed evidence of strong internal consistency reliability (Cronbach's alpha >0.80). A score ≥7 points was identified as an optimum threshold to identify patients whose AD is "not in control."Conclusions: No single validated instrument has been available to holistically evaluate patient-perceived AD control. The newly developed ADCT displays good-to-excellent content validity, construct validity, internal consistency, reliability, and discriminating ability. [ABSTRACT FROM AUTHOR]

Background and purpose: There is a need for new treatment options for moderate-to-severe atopic dermatitis (AD) in adults. Dupilumab, a fully human anti-interleukin-4 receptor a monoclonal antibody, has recently been approved for this indication. Methods: A pooled analysis of a phase 2a (NCT01548404) and a phase 2b (NCT01859988) study and a subanalysis of the 2b study evaluated the efficacy and safety of subcutaneous dupilumab 300 mg once weekly (qw) and every 2 weeks (q2w) in adults with moderate-to-severe AD. Results: Dupilumab significantly improved clinical outcomes in both analyses at week 12. Itch was significantly improved in the pooled analysis as measured by peak pruritus Numerical Rating Scale, 5-dimension pruritus scale, and SCORing Atopic Dermatitis (SCORAD) Visual Analog Scale (VAS) pruritus scores (all p < .0001 vs. placebo at week 12). Sleep loss was significantly improved (SCORAD VAS sleep loss score; p < .0001 vs. placebo at week 12); similar results were shown for the q2w dose. Dupilumab had an acceptable safety profile. Conclusions: Consistent with previous studies, dupilumab qw and q2w significantly improved signs and symptoms of AD at week 12, including improvements in itch and sleep loss. Implications for practice: Subcutaneous dupilumab is an effective new treatment option for adults with moderateto- severe AD. [ABSTRACT FROM AUTHOR]

Background: Emollients are a mainstay of treatment in atopic dermatitis (AD), a disease distinguished by skin bacterial dysbiosis. However, changes in skin microbiota when emollients are used as a potential AD preventative measure in infants remain incompletely characterized. Results: We compared skin barrier parameters, AD development, and bacterial 16S ribosomal RNA gene sequences of cheek, dorsal and volar forearm samples from 6-month-old infants with a family history of atopy randomized to receive emollients (n = 11) or no emollients (controls, n = 12). The emollient group had a lower skin pH than the control group. The number of bacterial taxa in the emollient group was higher than in the control group at all sites. The Streptococcus salivarius proportion was higher in the emollient versus control groups at all sites. S. salivarius proportion appeared higher in infants without AD compared to infants with AD. A decrease in S. salivarius abundance was further identified in a separate larger population of older children demonstrating an inverse correlation between AD severity at sampling sites and S. salivarius proportions. Conclusions: The decreased skin pH and the increased proportion of S. salivarius after long-term emollient use in infants at risk for developing AD may contribute to the preventative effects of emollients in high-risk infants. [ABSTRACT FROM AUTHOR]

Background: Data from early-stage studies suggested that interleukin (IL)-4 and IL-13 are requisite drivers of atopic dermatitis, evidenced by marked improvement after treatment with dupilumab, a fully-human monoclonal antibody that blocks both pathways. We aimed to assess the efficacy and safety of several dose regimens of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments.Methods: In this randomised, placebo-controlled, double-blind study, we enrolled patients aged 18 years or older who had an Eczema Area and Severity Index (EASI) score of 12 or higher at screening (≥16 at baseline) and inadequate response to topical treatments from 91 study centres, including hospitals, clinics, and academic institutions, in Canada, Czech Republic, Germany, Hungary, Japan, Poland, and the USA. Patients were randomly assigned (1:1:1:1:1:1), stratified by severity (moderate or severe, as assessed by Investigator's Global Assessment) and region (Japan vs rest of world) to receive subcutaneous dupilumab: 300 mg once a week, 300 mg every 2 weeks, 200 mg every 2 weeks, 300 mg every 4 weeks, 100 mg every 4 weeks, or placebo once a week for 16 weeks. We used a central randomisation scheme, provided by an interactive voice response system. Drug kits were coded, providing masking to treatment assignment, and allocation was concealed. Patients on treatment every 2 weeks and every 4 weeks received volume-matched placebo every week when dupilumab was not given to ensure double blinding. The primary outcome was efficacy of dupilumab dose regimens based on EASI score least-squares mean percentage change (SE) from baseline to week 16. Analyses included all randomly assigned patients who received one or more doses of study drug. This trial is registered with ClinicalTrials.gov, number NCT01859988.Findings: Between May 15, 2013, and Jan 27, 2014, 452 patients were assessed for eligibility, and 380 patients were randomly assigned. 379 patients received one or more doses of study drug (300 mg once a week [n=63], 300 mg every 2 weeks [n=64], 200 mg every 2 weeks [n=61], 300 mg every 4 weeks [n=65], 100 mg every 4 weeks [n=65]; placebo [n=61]). EASI score improvements favoured all dupilumab regimens versus placebo (p<0·0001): 300 mg once a week (-74% [SE 5·16]), 300 mg every 2 weeks (-68% [5·12]), 200 mg every 2 weeks (-65% [5·19]), 300 mg every 4 weeks (-64% [4·94]), 100 mg every 4 weeks (-45% [4·99]); placebo (-18% [5·20]). 258 (81%) of 318 patients given dupilumab and 49 (80%) of 61 patients given placebo reported treatment-emergent adverse events; nasopharyngitis was the most frequent (28% and 26%, respectively).Interpretation: Dupilumab improved clinical responses in adults with moderate-to-severe atopic dermatitis in a dose-dependent manner, without significant safety concerns. Our findings show that IL-4 and IL-13 are key drivers of atopic dermatitis.Funding: Sanofi and Regeneron Pharmaceuticals. INSET: Panel: Research in context.. [ABSTRACT FROM AUTHOR]

Background: Severe atopic dermatitis (AD) often cannot be adequately controlled with topical agents. The continuous use of current systemic therapies for AD is limited by end-organ toxicities. A safe and effective systemic therapy for patients with recalcitrant AD is greatly needed.Objective: To evaluate the potential safety and efficacy of efalizumab, an inhibitor of T cell activation and migration, in adults with severe AD.Methods: An investigator-initiated, prospective, open-label, pilot study was conducted involving ten subjects with severe AD. Subjects received an initial conditioning subcutaneous dose of efalizumab of 0.7 mg/kg followed by 1.0 mg/kg weekly for another 11 weeks for a total of 12 doses. The primary efficacy outcome was the change in the mean Eczema Area and Severity Index (EASI) score from baseline as measured at week 12. Monitoring of adverse events continued for 8 weeks after discontinuation of therapy.Results: EASI scores improved from a mean baseline score of 37.1 +/- 13.5 to 17.6 +/- 14.5 at week 12 (52.3% improvement; P < .0001). Six out of ten subjects reached at least a 50% improvement in EASI score by week 12. Pruritus levels decreased from 6.9 cm +/- 1.8 cm to 4.9 cm +/- 2.5 cm utilizing a visual analogue score (P < .015). Overall, efalizumab was well tolerated. There were three significant adverse events during the course of this study, including thrombocytopenia, viral gastroenteritis, and a subject with worsening of disease beyond baseline levels after drug discontinuation.Limitations: It is difficult to apply these findings to larger populations of patients with AD because this study lacked a control group and involved a small number of subjects with very severe disease. Long-term efficacy and safety of efalizumab in this population is not known.Conclusions: Efalizumab therapy resulted in significant clinical improvements in six of ten subjects with severe AD. Efalizumab may serve as a good alternative to current systemic immunosuppressants used for AD; however, double-blind placebo-controlled studies are needed to test its efficacy and safety. [ABSTRACT FROM AUTHOR]

A correction to the article "Impact of Oral Abrocitinib Monotherapy on Patient-Reported Symptoms and Quality of Life in Adolescents and Adult with Moderate-to-Severe Atopic Dermatitis: A Pooled Analysis of Patient-Reported Outcomes" in an issue is presented.

Atopic dermatitis affects a substantial number of children, many of whom seek initial treatment from their pediatrician or other primary care provider. Approximately two-thirds of these patients have mild disease and can be adequately managed at the primary care level. However, recent treatment guidelines are written primarily for use by specialists and lack certain elements that would make them more useful to primary care providers. This article evaluates these recent treatment guidelines in terms of evaluation criteria, treatment recommendations, usability, accessibility, and applicability to nonspecialists and integrates them with clinical evidence to present a streamlined severity-based treatment model for the management of a majority of atopic dermatitis cases. Because each patient's situation is unique, individualization of treatment plans is critical as is efficient communication and implementation of the plan with patients and caregivers. Specifically, practical suggestions for individualizing, optimizing, implementing, and communicating treatment plans such as choosing a moisturizer formulation, avoiding common triggers, educating patients/caregivers, providing written treatment plans, and scheduling physician follow-up are provided along with a discussion of available resources for patients/caregivers and providers. [ABSTRACT FROM AUTHOR]

Background: Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis.Methods: In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids were enrolled at 161 hospitals, clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a central interactive voice/web response system, stratified by severity and global region. All three groups were given concomitant topical corticosteroids with or without topical calcineurin inhibitors where inadvisable for topical corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted on the basis of disease activity. Coprimary endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-point or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses included all randomised patients; week 52 efficacy included patients who completed treatment by US regulatory submission cutoff. This study is registered with ClinicalTrials.gov, NCT02260986.Findings: Between Oct 3, 2014, and July 31, 2015, 740 patients were enrolled: 319 were randomly assigned to dupilumab qw plus topical corticosteroids, 106 to dupilumab q2w plus topical corticosteroids, and 315 to placebo plus topical corticosteroids. 623 (270, 89, and 264, respectively) were evaluable for week 52 efficacy. At week 16, more patients who received dupilumab plus topical corticosteroids achieved the coprimary endpoints of IGA 0/1 (39% [125 patients] who received dupilumab plus topical corticosteroids qw and 39% [41 patients] who received dupilumab q2w plus topical corticosteroids vs 12% [39 patients] who received placebo plus topical corticosteroids; p<0·0001) and EASI-75 (64% [204] and 69% [73] vs 23% [73]; p<0·0001). Week 52 results were similar. Adverse events were reported in 261 (83%) patients who received dupilumab qw plus topical corticosteroids, 97 (88%) patients who received dupilumab q2w, and 266 (84%) patients who received placebo, and serious adverse events in nine (3%), four (4%), and 16 (5%) patients, respectively. No significant dupilumab-induced laboratory abnormalities were noted. Injection-site reactions and conjunctivitis were more common in patients treated with dupilumab plus topical corticosteroids-treated patients than in patients treated with placebo plus topical corticosteroids.Interpretation: Dupilumab added to standard topical corticosteroid treatment for 1 year improved atopic dermatitis signs and symptoms, with acceptable safety.Funding: Sanofi and Regeneron Pharmaceuticals Inc. [ABSTRACT FROM AUTHOR]