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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.)

Bermekimab is a human-derived recombinant monoclonal antibody that exhibits immunoregulatory activity by specifically blocking interleukin-1α activity. Four phase 2 studies evaluated efficacy and safety of bermekimab in patients with moderate-to-severe atopic dermatitis (AD). In addition, a novel human skin explant model was developed to assess bermekimab pharmacokinetics/pharmacodynamics and proteomic/transcriptomic effects. Study 1 (NCT03496974, N = 38) was an open-label, dose escalation study of subcutaneous bermekimab (200 mg or 400 mg). Study 2 (NCT04021862, N = 87) was a double-blind, placebo-controlled, randomized (1:1:1) study of subcutaneous bermekimab (400 mg every week (qw) or every 2 weeks) or placebo. GENESIS (NCT04791319, N = 198) was a double-blind, placebo- and active-comparator-controlled, randomized (1:1:2:2) study of placebo, subcutaneous bermekimab (350 mg or 700 mg qw), or dupilumab. LUNA (NCT04990440, N = 6) was a double-blind, placebo-controlled, randomized (4:1) study of intravenous bermekimab 800 mg qw or placebo. A novel human ex vivo skin pharmacodynamic assay supported phase 0 (NCT03953196) and phase 1 (NCT04544813) studies. In Study 1, 400 mg subcutaneous bermekimab showed improvement in efficacy assessments (e.g., ≥ 75% improvement of EASI over baseline, IGA 0/1, and worst itch); however, efficacy was not confirmed in Study 2 or GENESIS. Consequently, GENESIS and LUNA were terminated early. The novel human ex vivo skin pharmacodynamic assay demonstrated that bermekimab reduced downstream skin injury responses. Although bermekimab showed potential as an AD treatment in preclinical and early open-label trials, larger controlled studies (Study 2 and GENESIS) did not confirm those initial results., (© 2024. The Author(s).)

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).)

Purpose: Ruxolitinib (selective Janus kinase [JAK] 1 and JAK2 inhibitor) cream demonstrated efficacy and safety in patients with atopic dermatitis (AD) in the phase 3 TRuE-AD studies. In TRuE-AD1/TRuE-AD2 (NCT03745638/NCT03745651), adults and adolescents with mild to moderate AD were randomized to apply twice-daily ruxolitinib cream or vehicle for eight weeks. Here, we evaluated the efficacy and tolerability of ruxolitinib cream by anatomic region, focusing on head/neck (HN) lesions that are typically difficult to manage and disproportionately affect quality of life (QoL). Materials and methods: Eczema Area and Severity Index (EASI) responses in anatomic regions were evaluated in the pooled population ( N  = 1208) and among patients with baseline HN involvement ( n  = 663). Itch, Investigator's Global Assessment (IGA), QoL, and application site tolerability were also assessed. Results: By Week 2 (earliest assessment), ruxolitinib cream application resulted in significant improvements across all EASI anatomic region subscores and AD signs versus vehicle, with further improvements through Week 8. Significantly more patients with HN involvement who applied ruxolitinib cream versus vehicle achieved clinically meaningful improvements in itch, IGA, and QoL. Application site reactions with ruxolitinib cream were infrequent (<3%), including in patients with HN involvement. Conclusions: These results support the use of ruxolitinib cream for AD treatment across all anatomic regions, including HN.

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.)

Studies examining the real-world treatment satisfaction in adults with atopic dermatitis (AD) and the physicians who treat adults with AD are scarce. We sought to characterize treatment satisfaction of adults with AD and physicians' perceived patient satisfaction with AD treatment. We performed a cross-sectional study of adults > = 18 years of age (modified AD UK Working Party Criteria, age onset < = 18 [N = 767]) with AD and a parallel-physician survey among allergists/immunologists [N = 148], dermatologists [N = 149] and primary care medicine [N = 104]. Logistic regression models were used to examine factors associated with patient treatment satisfaction (PTS) or physician-perceived patient treatment satisfaction (pPTS). Factors associated with increased PTS included female, older age, and receiving a written eczema action plan (EAP). Severe AD, itch, pain, and insomnia, greater impact on partner relationships, feeling not adequately informed about AD causes, and being separated, never married, or living with a partner was associated with less PTS. From the physician's perspective, mild AD and development of EAP was associated with increase pPTS, whereas being in practice longer was associated with less pPTS. Limitations include the potential for misclassification of AD and the inability to match AD patients to individual physicians. Recognizing which factors are associated with treatment satisfaction can help inform counseling and decision-making strategies, including the use of an eczema action plan, and support patient-physician outcomes alignment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Conflicts of interest L.E. and M.N. are employees of and shareholders in Sanofi. P.M. and I.G. were employees of and shareholders in Sanofi, and A.G. was an employee of and shareholder in Regeneron Pharmaceuticals, Inc. when the study was conducted. J.C. is an employee and shareholder of Regeneron. T.M.B., L.N. and S.E.F. are employees of RTI Health Solutions, which received research funding for the current study. P.A.L. reports research funding from Sanofi, Regeneron Pharmaceuticals, Inc. and AbbVie; is on the speaker’s bureau for Sanofi, Regeneron Pharmaceuticals, Inc., Pfizer and Galderma; and reports participating on consulting/advisory boards for UCB, Dermavant, Sanofi, Regeneron Pharmaceuticals, Inc., Dermira, Pfizer, LEO Pharma, AbbVie, Kiniksa, Eli Lilly, Menlo Therapeutics, Galderma, IntraDerm, Exeltis and Realm Therapeutics. E.L.S. has received grants/research support from Amgen, Celgene, Chugai, Galderma, Genentech, MedImmune, Sanofi, Regeneron Pharmaceuticals, Inc., Tioga, Vanda Pharmaceuticals and Lilly; and is a consultant for Anacor, Celgene, Galderma, Genentech, Medicis, Sanofi, Regeneron Pharmaceuticals, Inc. and Merck. B.L. is a speaker for AbbVie, Sun, Novartis, Eli Lilly, UCB, Regeneron Pharmaceuticals, Inc. and Sanofi; an investigator for AbbVie, Celgene, Sun Pharma, Novartis, Eli Lilly, Regeneron Pharmaceuticals, Inc., Sanofi, Incyte and Corrona Registry; and a consultant for AbbVie, Sun, Novartis, Eli Lilly, UCB, Regeneron Pharmaceuticals, Inc., Sanofi, Bristol Myers Squibb, Incyte and Corrona Registry.

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

Background: Rademikibart (CBP-201) is a next-generation IL-4 receptor alpha-targeting antibody., Objective: We sought to evaluate rademikibart in adults with moderate to severe atopic dermatitis., Methods: A total of 226 patients were randomized, double-blind, to subcutaneous rademikibart (300 mg every 2 weeks [Q2W], 150 mg Q2W, 300 mg every 4 weeks [Q4W]; plus 600-mg loading dose) or placebo. Randomization began in July 2020. The trial was completed in October 2021., Results: The WW001 phase 2 trial achieved its primary end point: significant percent reduction from baseline in least-squares mean Eczema Area Severity Index (EASI) to week 16 with rademikibart 300 mg Q2W (-63.0%; P = .0007), 150 mg Q2W (-57.6%; P = .0067), 300 mg Q4W (-63.5%; P = .0004) versus placebo (-39.7%). EASI scores decreased significantly with 300 mg Q2W and Q4W at the earliest assessment (week 2), with no evidence of plateauing by week 16. Significant improvements were also observed in secondary end points, including pruritus. Across the primary and secondary end points, efficacy tended to be comparable with 300 mg Q2W and Q4W dosing. Rademikibart and placebo had similar, low incidence of treatment-emergent adverse events (TEAEs) (48% vs 54%), serious TEAEs (1.8% vs 3.6%), TEAEs leading to treatment discontinuation (1.2% vs 1.8%), conjunctivitis of unspecified cause (2.9% vs 0%), herpes (0.6% vs 1.8%), and injection-site reactions (1.8% vs 1.8%). Although no discontinuations were attributed to coronavirus disease 2019, pandemic-related restrictions likely had an impact on trial conduct., Conclusions: Rademikibart was efficacious and well tolerated at Q2W and Q4W intervals. Q4W dosing is a more convenient frequency than approved for current therapies., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The Harmonising Outcome Measures for Eczema (HOME) initiative has agreed upon the Core Outcome Set (COS) for use in atopic dermatitis (AD) clinical trials, but additional guidance is needed to maximize its uptake., Objectives: To provide answers to some of the commonly asked questions about using the HOME COS; to provide data to help with the interpretation of trial results; and to support sample size calculations for future trials., Methods and Results: We provide practical guidance on the use of the HOME COS for investigators planning clinical trials in patients with AD. It answers some of the common questions about using the HOME COS, how to access the outcome measurement instruments, what training/resources are needed to use them appropriately and clarifies when the COS is applicable. We also provide exemplar data to inform sample size calculations for eczema trials and encourage standardized data collection and reporting of the COS., Conclusions: By encouraging adoption of the COS and facilitating consistent reporting of outcome data, it is hoped that the results of eczema trials will be more comprehensive and readily combined in meta-analyses and that patient care will subsequently be improved., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Therapeutic options for people with moderate or severe atopic dermatitis refractory to topical therapy have rapidly expanded in recent years. These new targeted immunomodulatory agents-biologics and Janus kinase (JAK) inhibitors-have each demonstrated high levels of efficacy and acceptable safety in mostly placebo-controlled clinical trials for atopic dermatitis, but there is no universally applicable algorithm to help choose between them for a given patient. Hence, patients and physicians should utilize shared decision making, discussing efficacy, safety, mode of delivery, monitoring, costs, speed of onset, and other factors to reach individualized treatment decisions. In this review, we try to aid shared decision making by summarizing the efficacy, safety, and monitoring of biologics and oral JAK inhibitors for adults with atopic dermatitis. Network meta-analyses suggest that higher doses of abrocitinib and upadacitinib are more effective than biologics. They also show that, among biologics, dupilumab is likely more effective than tralokinumab and lebrikizumab. Biologics are generally considered safer than JAK inhibitors, although concerns about JAK inhibitors are mainly extrapolated from older generation JAK inhibitors used in higher-risk populations. We also outline evidence and considerations for choosing and using systemic immunomodulatory treatments for special populations including pregnant individuals, those with human immunodeficiency virus (HIV), hepatitis B and C, end stage kidney disease, and older adults., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This is a summary of the original article "An Anti-OX40 Antibody to Treat Moderate-to-Severe Atopic Dermatitis: a Multicentre, Double-blind, Placebo-Controlled Phase 2b Study". Atopic dermatitis (AD) is an inflammatory skin disease caused by a complex interplay of genetic factors, alterations to the skin microenvironment, and immune dysregulation, including T cells that have become uncontrolled. Rocatinlimab is an investigational agent that blocks OX40, a receptor on activated T cells that has an important role in inflammatory conditions such as AD. This summary of research provides an overview of a previously published article on the results of a phase 2b study of patients with moderate-to-severe AD who were treated with different doses of rocatinlimab or placebo and followed for up to 56 weeks. Rocatinlimab significantly improved the symptoms of AD and was well tolerated. The most common adverse events were fever, nasopharyngitis, and chills. This study supports rocatinlimab as a potentially safe and effective treatment for moderate-to-severe AD., (© 2024. The Author(s).)

Disparities in environmental and social determinants of health (DOH) are associated with morbidity in atopic dermatitis (AD). The socioecological model (SEM) is a framework that can be applied to better understand how such DOH impacts patients with AD. We include a case scenario of a remote Indigenous patient reflective of real-world situations of living with AD and examine relevant impact, gaps in knowledge, and further research needs. This review highlights a variety of social and environmental exposures as important DOH which must be addressed to achieve optimal management in AD. The "rainbow model" is a modified framework to help illustrate how complex environmental and social forces impact both AD presentation and therapeutic success. However, practical applications and outcome metrics for health promotion are limited. An inter- and transdisciplinary approach is paramount to address the complex challenges associated with AD care, as well as multistakeholder approach integrating culturally-competent equitable health frameworks. This review underscores the importance of expanding the focus of AD management beyond basic science and clinical trials to recognize and address health disparities and to promote optimal health and well-being in patients with AD, and contributes a working approach to mapping the complex interventions and patient-oriented research needed using a focus on remote North American Indigenous patients affected by AD., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis is a common chronic, relapsing, and remitting inflammatory skin disorder associated with cutaneous dysbiosis. Current treatment options often fail to adequately control the disease and have unfavorable safety profiles. There is a need for new options that address these treatment shortcomings., Objective: The aim of the study was to evaluate the efficacy, safety, and tolerability of FB-401, a live therapeutic product of 3 strains of Roseomonas mucosa, compared to matching placebo applied topically 3 times per week to participants ages ≥2 years of age with mild-to-moderate atopic dermatitis., Methods: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. The primary outcome was the proportion of participants with 50% improvement in Eczema Area and Severity Index score from baseline at week 16. 154 subjects aged 2 or older with a clinical diagnosis of atopic dermatitis as defined by Hanifin and Rajka criteria with mild or moderate severity were randomized 1:1 via interactive web response system to FB-401 or placebo., Results: The proportion of subjects who achieved the primary outcome was similar between both treatment groups, with no significant treatment group differences observed at any post-baseline visit. The number of treatment-emergent adverse events and the number of subjects with at least one were similar across treatment groups. One serious adverse event not related to treatment was reported. No treatment-emergent adverse events led to treatment discontinuation or study discontinuation., Conclusions: FB-401 showed an acceptable safety profile but failed to prove superior to placebo in treating children and adults with mild-to-moderate atopic dermatitis., (© 2023 S. Karger AG, Basel.)

Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background 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. 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)., (© 2023. The Author(s).)

Background: Baricitinib, a selective Janus kinase (JAK)1/JAK2 inhibitor, is approved for treatment of moderate-to-severe atopic dermatitis (AD) in adults., Objectives: We report integrated baricitinib safety data in patients with up to 3.9-years exposure., Methods: Three datasets from the integrated AD clinical trial program were analyzed: placebo-controlled, 2-mg-4-mg extended, and All-bari. Data cutoffs were up to 21-December-2021 for long-term extension studies. Proportions of patients with events and incidence rates (IR)/100 patient years (PY) at risk were calculated., Results: 2636 patients received baricitinib for 4628.4 PY. Discontinuation due to adverse events was low (IR = 3.4). IRs in All-bari were: serious adverse events, 5.2; infection, 67.2 (any infection), 6.7 (herpes simplex), 2.8 (herpes zoster), and 0.3 (opportunistic infections). Adverse events of special interest in All-bari included seven patients with positively adjudicated major adverse cardiovascular events (MACE) (IR = 0.15), three pulmonary emboli (PE) (IR = 0.06), 14 malignancies excluding nonmelanoma skin cancer (IR = 0.3), one gastrointestinal perforation (IR = 0.02), and four deaths (IR = 0.1). No deep vein thromboses (DVT) or tuberculosis were reported., Conclusion: In this analysis, baricitinib maintained a similar safety profile to earlier analyses with no new safety signals. Rates of MACE, DVT/PE, malignancies, and serious infections were within ranges of background rates in patients with AD., Clinicaltrials.gov: NCT02576938 (JAHG), NCT03334396 (JAHL; BREEZE-AD1), NCT03334422 (JAHM; BREEZE-AD2), NCT03334435 (JAHN; BREEZE-AD3), NCT03428100 (JAIN; BREEZE-AD4), NCT03435081 (JAIW; BREEZE-AD5), NCT03559270 (JAIX; BREEZE-AD6), NCT03733301 (JAIY; BREEZE-AD7).

Background: Real-world data on the effectiveness of systemic therapy in atopic dermatitis (AD) are limited., Methods: Adult patients with AD in the CorEvitas AD registry (2020-2021) who received systemic therapies for 4-12 months prior to enrollment were included based on disease severity: body surface area (BSA) 0%-9% and BSA ≥10%. Demographics, clinical characteristics, and outcomes were assessed using descriptive statistics. Pairwise effect sizes (ES) were used to compare BSA groups., Results: The study included 308 patients (BSA 0%-9%: 246 [80%]; BSA ≥10%: 62 [20%]). Despite systemic therapy, both BSA groups reported the use of additional topical therapy and the presence of lesions at difficult locations. Moderate-to-severe AD (vIGA-AD ® ) was reported by 11% (BSA 0%-9%) and 66% (BSA ≥10%; ES = 0.56) of patients. Mean disease severity scores: total BSA (2% and 22%; ES = 3.59), EASI (1.1 and 11.1; ES = 2.60), and SCORAD (12.1 and 38.0; ES = 1.99). Mean scores for PROs: DLQI (3.7 and 7.5; ES = 0.75), and peak pruritus (2.2 and 4.5; ES = 0.81). Inadequate control of AD was seen in 27% and 53% of patients (ES = 0.23)., Conclusions: Patients with AD experience a high disease burden despite systemic treatment for 4-12 months. This study provides potential evidence of suboptimal treatment and the need for additional effective treatment options for AD.

Ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and JAK2. In two phase 3 studies in adults and adolescents (aged ≥12 years) with atopic dermatitis (AD; TRuE-AD1/TRuE-AD2), significantly more patients who applied ruxolitinib cream versus vehicle cream achieved Investigator's Global Assessment treatment success (IGA-TS; IGA score of 0/1 with ≥2-point improvement from baseline) at week 8 (primary endpoint). This post hoc analysis evaluated the efficacy, safety, and disease control of ruxolitinib cream in patients with AD who did not achieve IGA-TS at week 8. Patients in TRuE-AD1/TRuE-AD2 (N = 1249) were randomized 2:2:1 to apply twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 weeks followed by a long-term safety period in which patients applied ruxolitinib cream as needed. In this pooled analysis, clinically meaningful response thresholds included ≥50% improvement in the Eczema Area and Severity Index, ≥2-point reduction in the Itch Numerical Rating Scale, ≥4-point improvement in the Dermatology Life Quality Index (DLQI) or ≥6-point improvement in Children's DLQI, and ≥1-point reduction in IGA from baseline. Among patients who did not achieve IGA-TS at week 8 (n = 584), significantly more patients who applied either strength ruxolitinib cream versus vehicle achieved each response threshold at week 8. A response in ≥1 clinically meaningful endpoint was achieved in significantly more patients who applied ruxolitinib cream (93.4%/90.9% for 0.75%/1.5% ruxolitinib cream, respectively) versus vehicle (69.0%, both P < 0.0001). Progressive improvements in disease control were observed, with many patients achieving IGA-TS by week 52 (55.2%/56.3% for 0.75%/1.5% ruxolitinib cream, respectively). Ruxolitinib cream was well tolerated during the 52-week study in this patient population. Taken together, these results demonstrate that most patients with AD who did not achieve IGA-TS at week 8 have clinically meaningful responses to ruxolitinib cream, and continued therapy beyond 8 weeks could result in additional benefit., (© 2023 Incyte Corporation and The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Purpose: Environmental factors such as bathing may play a role in atopic dermatitis (AD) development. This analysis utilized data from the Community Assessment of Skin Care, Allergies, and Eczema (CASCADE) Trial (NCT03409367), a randomized controlled trial of emollient therapy for AD prevention in the general population, to estimate bathing frequency and associated factors within the first 9 weeks of life., Methods: Data were collected from 909 parent/newborn dyads recruited from 25 pediatric and family medicine clinics from the Meta-network Learning and Research Center (Meta-LARC) practice-based research network (PBRN) consortium in Oregon, North Carolina, Colorado, and Wisconsin for the CASCADE trial. Ordinal logistic regression was used to conduct a cross-sectional analysis of the association between bathing frequency (measured in baths per week) and demographic, medical, and lifestyle information about the infant, their family, and their household. Variables were selected using a backwards-stepwise method and estimates from the reduced model are reported in the text., Results: Moisturizer use (OR = 2.03, 95% CI: 1.54-2.68), Hispanic or Latino ethnicity (OR = 1.97, 95% CI: 1.42-2.72), a parental education level lower than a 4-year college degree (OR = 2.48, 95% CI: 1.70-3.62), living in North Carolina or Wisconsin (compared to Oregon; OR = 2.12 and 1.47, 95% CI: 1.53-2.93 and 1.04-2.08, respectively), and increasing child age (in days; OR = 1.02, 95% CI: 1.01-1.02) were significantly associated with more frequent bathing, while pet ownership (OR = 0.67, 95% CI: 0.52-0.87) was significantly associated with less frequent bathing., Conclusions: We found significant ethnic, geographic, and socioeconomic variation in bathing frequency before 9 weeks of age that may be of relevance to AD prevention studies., (© 2023 Wiley Periodicals LLC.)

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

Background: While the majority of patients with atopic dermatitis (AD) achieve disease control with dupilumab treatment, there is variability in which patients achieve clear disease. The predictors of these responses are currently unclear. Integrated models were developed to evaluate the exposure-response (E-R) relationship of dupilumab in children, adolescents, and adults with AD., Methods: Data from six Phase II and III clinical studies were pooled (2,366 adults [> 18 years], 243 adolescents [≥ 12 to < 18 years] and 359 children [≥ 6 to < 12 years]) for model development. Efficacy was assessed using the Eczema Area and Severity Index (EASI) and Investigator's Global Assessment (IGA). Indirect response models were applied to link measures of efficacy and functional serum dupilumab concentrations. The covariates on individual placebo-corrected response were assessed. Clinical trial scenarios were simulated to compare E-R relationships across age groups. Safety was not explored., Results: After correcting for differences in placebo response and dupilumab exposure: 1) older age, higher body weight, lower baseline thymus and activation-regulated chemokine, and Asian race were associated with slightly lower EASI response, and no clear covariates were identified on IGA response; 2) clinical trial simulations generally showed slightly higher response at a given dupilumab concentration in children compared to adults and adolescents with severe and moderate AD., Conclusions: The collectively tested covariates explain some of the variability in dupilumab response in patients with AD. Patients in all age groups showed adequate response to dupilumab; however, children showed slightly higher drug effects compared to adults and adolescents at equivalent concentrations., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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

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

Atopic dermatitis (AD) is a chronic inflammatory skin disease that can significantly decrease quality of life. AD is commonly associated with comorbidities including ocular surface disease (OSD). Conjunctivitis is the most common OSD associated with AD and can increase in incidence with use of monoclonal antibody biologics that target the type 2 inflammatory pathway. The objective of this review is to raise awareness of comorbid OSD in AD patients that dermatologists may encounter, with a focus on conjunctivitis, and equip dermatologists to address mild ocular concerns. We provide background on the subtypes and pathogenesis of comorbid OSD in AD patients and describe OSD associated with type 2 inflammation-inhibiting AD biologics. We also discuss screening and diagnosis, recommended treatment options for dermatologists, and when to refer to an eye care specialist. This multispecialty approach aims to support the overall health of AD patients and provide optimal patient care., Competing Interests: Conflicts of interest Dr Shi is on the board of directors for the Hidradenitis Suppurativa Foundation (HSF); an advisor for the National Eczema Association; is a stock shareholder of Learn Health; and has served as an advisory board member, investigator, speaker, and/or received research funding from AbbVie, Altus Lab/cQuell, Aristea Therapeutics, Boehringer Ingelheim, Burt's Bees, Dermira, Ely Lilly, Galderma, GPSkin, Incyte, Kiniksa, LEO Pharma, Menlo Therapeutics, MYOR, Novartis, Pfizer, Polyfins Techology, Regeneron, Sanofi Genzyme, Skin Actives Scientific, SUN Pharma, Target-PharmaSolutions, and UCB. Dr Chamberlain is a medical advisor and/or investigator for Aslan Pharmaceuticals, Beyeonics, Cambium, Kowa, LEO Pharma, Noveome, Oyster Point, Regeneron, and Trefoil Therapeutics. Dr Siegfried receives contracted research fees, consulting fees, honoraria, and/or is an investigator for AbbVie, AI Therapeutics, ASLAN Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, Incyte, Janssen, LEO Pharma, Novan, Novartis, Pierre Fabre, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Verrica; and is a member of the Research Advisory Committee of the National Eczema Association. Dr Cooper has served as an advisory board member for LEO Pharma and as a speaker for Pfizer. Dr Beckman reports research grants/funding from Aerie, Alcon, Allergan, Avellino, Bausch & Lomb, BioTissue, Bruder, Dompe, Eyepoint, Eyevance, Glaukos, Glint, Johnson & Johnson, Kala, LEO Pharma, Novartis, Ocular Science, Ocular Therapeutix, Sun, TearLab, Visus, and Zeiss. Dr Lio reports research grants/funding from AbbVie, AOBiome, and Regeneron/Sanofi Genzyme; is on the speaker's bureau for Eli Lilly, Galderma, Incyte, LEO Pharma, L'Oreal, Pfizer, and Regeneron/Sanofi Genzyme; and reports consulting/advisory boards for AbbVie, Almirall, Altus Labs (stock options), Amyris, AOBiome, Arbonne, ASLAN Pharmaceuticals, Bodewell, Burt's Bees, Dermavant, Eli Lilly, Exeltis, Galderma, IntraDerm, Johnson & Johnson, LEO Pharma, L'Oreal, Menlo Therapeutics, Micreos (stock options), Pfizer, Pierre-Fabre, Realm Therapeutics, Regeneron/Sanofi Genzyme, Theraplex, and Unilever. In addition, Dr Lio has a patent pending for a Theraplex product with royalties paid, and is a Board member and Scientific Advisory Committee Member of the National Eczema Association. Dr Paller is an investigator (contract to institution) for AbbVie, AnaptysBio, Eli Lilly, Incyte, Janssen, KrystalBio, Regeneron, and UCB; consultant with honorarium for Abbvie, Abeona, Alcimed, Almirall, Amagma, Anaptysbio, Arena, Azitra, BiomX, Boehringer Ingeheim, Castle Biosciences, Catawba, Dermira, Eli Lilly, Exicure, Forte, Kamari, LEO Pharma, Lifemax, NAOS, Novartis, Pfizer, Phoenix, Pierre Fabre, Regeneron, Sanofi/Genzyme, Seanergy, Trifecta, and UCB; and is on the Data Safety Monitoring Board for AbbVie, Bausch, Galderma, and Novan. Dr Simpson reports grants and/or personal fees from AbbVie, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, FortéBio, Galderma, Incyte, Kyowa Kirin, LEO Pharma, MedImmune, Menlo Therapeutics, Merck, Novartis, Ortho Dermatologics, Pfizer, Pierre Fabre Dermo Cosmetique, Regeneron, Sanofi, Tioga, and Valeant., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest See Appendix S1 for full Conflicts of Interest list.

Background: Tolerability issues including acne, nausea, and headache have been reported with Janus kinase (JAK) inhibitors for moderate-to-severe atopic dermatitis (AD). Objectives: To report outcomes of tolerability adverse events (AEs) for baricitinib, a JAK1/JAK2 inhibitor, in patients with moderate-to-severe AD. Methods: Acne, headache, and gastrointestinal AEs are reported from placebo-controlled and long-term extensions of pooled data in the baricitinib AD clinical trial program. Proportions of patients with AEs, incidence rates (IRs)/100 patient-years at risk, and median time to onset/duration of AEs were calculated. Results: In 2531 patients treated with baricitinib, most AEs were mild to moderate in severity. Headache was the most common AE of tolerability (median of 14-26 days after first dose of baricitinib, lasting ≤3 days). IRs of acne were <5 in any group lasting up to a median of 90 days with no severe AEs. Diarrhea was the most common gastrointestinal AE, lasting a median of ≤7 days. There were few study drug interruptions (n = 6) and permanent discontinuations (n = 5) for tolerability AEs. Conclusions: For the AEs of tolerability analyzed, baricitinib appears to be well tolerated. Overall, the frequency of these AEs in patients being treated for moderate-to-severe AD was low with few leading to study drug interruption or permanent discontinuation. Clinical Trial Registration number: NCT02576938; NCT03334396; NCT03334422; NCT03428100; NCT03435081; NCT03733301; NCT03334435; NCT03559270.

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., (© 2023. The Author(s).)

Despite the need for improved eczema therapies and a rapid increase in available eczema clinical trials, participation remains low. The aim of this study was to identify factors associated with clinical trial awareness, interest, and barriers to enrolment and participation. An online survey, administered 1 May to 6 June 2020 to adults (≥ 18 years) with eczema in the USA, was analysed. Among 800 patients included, mean age was 49.4 years, most respondents were female (78.1%), White (75.4%), non-Hispanic (91.4%), and geographically living in an urban/suburban area (Rural-Urban Continuum Codes (RUCC) 1-3, 90.8%). Only 9.7% of respondents reported previous participation in clinical trials, while 57.1% had considered participation and 33.2% never considered participation. Higher satisfaction with current eczema therapy, clinical trial literacy, and confidence in finding eczema trial information were all associated with clinical trial awareness, interest, and successful participation. Younger age and having atopic dermatitis were associated with increased awareness, while female gender was a barrier to interest and successful participation.

Importance: Safe and effective long-term treatments for adolescents with moderate to severe atopic dermatitis (AD) are limited., Objective: To evaluate the efficacy and safety of interleukin-13-targeted treatment with tralokinumab monotherapy in adolescents with AD., Design, Setting, and Participants: The 52-week, randomized, double-blinded, placebo-controlled, phase 3 ECZTRA 6 trial was conducted from July 17, 2018, through March 16, 2021, at 72 centers across 10 countries in North America, Europe, Asia, and Australia. Enrolled patients were 12 to 17 years old with moderate to severe AD (Investigator's Global Assessment [IGA] score ≥3; Eczema Area and Severity Index [EASI] ≥16)., Interventions: Patients were randomized (1:1:1) to tralokinumab (150 or 300 mg) or placebo every 2 weeks for 16 weeks. Patients with an IGA score of 0 (clear) or 1 (almost clear) and/or 75% or higher improvement in EASI (EASI 75) at week 16 without rescue medication received maintenance treatment; other patients switched to open-label tralokinumab, 300 mg, every 2 weeks., Main Outcomes and Measures: Primary end points at week 16 were an IGA score of 0 or 1 and/or achieving EASI 75. Key secondary end points were a reduction of Adolescent Worst Pruritus Numeric Rating Scale of 4 or more, change in SCORing AD, and change in Children's Dermatology Life Quality Index from baseline to week 16. Safety end points were the number of adverse events and serious adverse events., Results: Of 301 patients randomized, 289 comprised the full analysis set (median [IQR] age, 15.0 [13.0-16.0] years; 149 [51.6%] male). More patients receiving tralokinumab, 150 mg, (n = 98), and tralokinumab, 300 mg (n = 97), achieved an IGA score of 0 or 1 without rescue medication at week 16 (21 [21.4%] and 17 [17.5%], respectively) vs placebo (n = 94; 4 [4.3%]) (adjusted difference, 17.5% [95% CI, 8.4%-26.6%]; P < .001 and 13.8% [95% CI, 5.3%-22.3%]; P = .002, respectively). More patients receiving tralokinumab, 150 mg (28 [28.6%]), and tralokinumab, 300 mg, (27 [27.8%]) vs placebo (6 [6.4%]) achieved EASI 75 without rescue at week 16 (adjusted difference, 22.5% [95% CI, 12.4%-32.6%]; P < .001 and 22.0% [95% CI, 12.0%-32.0%]; P < .001, respectively). Proportions of patients with Adolescent Worst Pruritus Numeric Rating Scale reduction of 4 or more from baseline were greater with tralokinumab, 150 mg (23.2%), and tralokinumab, 300 (25.0%), vs placebo (3.3%), and adjusted mean changes were greater in SCORing AD with tralokinumab, 150 mg (-27.5), and tralokinumab, 300 mg (-29.1), vs placebo (-9.5) and in Children's Dermatology Life Quality Index with tralokinumab, 150 mg (-6.1), and tralokinumab, 300 mg (-6.7), vs placebo (-4.1) at week 16. At week 52, tralokinumab efficacy was maintained without rescue in more than 50% of patients meeting primary end point(s) at week 16. In the open-label phase, IGA score of 0 or 1 and EASI 75 were achieved in 33.3% and 57.8%, respectively, at week 52. Tralokinumab was well tolerated, without frequency of conjunctivitis increasing through week 52., Conclusions and Relevance: In this randomized clinical trial, tralokinumab was efficacious and well tolerated, supporting its value for treating adolescents with moderate to severe AD., Trial Registration: ClinicalTrials.gov Identifier: NCT03526861.

Background: Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13., Objectives: To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967)., Methods: Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator's Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period., Results: After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity., Conclusions: After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data., Competing Interests: Conflicts of interest A.B. has served as a speaker (received honoraria) for AbbVie, Arcutis, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron, Sanofi and UCB; served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Arena, ASLAN Pharmaceuticals, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome and Xencor; and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, ACELYRIN, Almirall, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma and UCB Pharma. J.P.T. is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, ASLAN Pharmaceuticals, Union Therapeutics, Eli Lilly and Company, LEO Pharma, Pfizer, Regeneron and Sanofi Genzyme; a speaker for AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Pfizer, Regeneron and Sanofi Genzyme; and has received research grants from Pfizer, Regeneron and Sanofi Genzyme. E.G.-Y. is a consultant for AbbVie, Almirall, Amgen, Asana Biosciences, Boehringer Ingelheim, Cara Therapeutics, Celgene, Concert, DBV, Dermira, DS Biopharma, Eli Lilly and Company, EMD Serono, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Mitsubishi Tanabe, Pfizer, RAPT Therapeutics, Regeneron, Sanofi, Sienna Biopharma and Union Therapeutics; and reports institute grants for research from AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, Boehringer Ingelheim, Celgene, Dermavant, DS Biopharma, Eli Lilly and Company, Glenmark, Galderma, Innovaderm, Janssen, Kiniska, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Ralexar, Regeneron, Sienna Biopharma, UCB and Union Therapeutics. T.B. has been a speaker and/or consultant and/or investigator for AbbVie, Affibody, Almirall, AnaptysBio, Arena, Asana Biosciences, ASLAN Pharmaceuticals, Bayer Health, BioVerSys, Boehringer-Ingelheim, Bristol Myers Squibb, Connect Pharma, Dermavant, Domain Therapeutics, EQRx, Galderma, Glenmark, GSK, Incyte, Innovaderm, IQVIA, Janssen, Kirin, Kymab, LEO Pharma, LG Chem, Lilly, L’Oréal, MSD, Novartis, Numab, OM Pharma, Pfizer, Pierre Fabre, Q32bio, RAPT, Sanofi/Regeneron and UCB; he is the founder and chairman of the board of the nonprofit biotechnology company Davos Biosciences. E.S.-B. has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AbbVie, Novartis, Almirall, LEO Pharma, Sanofi, Pfizer and Eli Lilly and Company. E.S. reports personal fees from AbbVie, Amgen, Arena Pharmaceuticals, ASLAN Pharmaceuticals, Boston Consulting Group, Collective Acumen (CA, USA), Dermira, Eli Lilly and Company, Evidera, Excerpta Medica, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin Pharmaceutical Development, LEO Pharma, Medscape, Merck, Pfizer, Physicians World, Regeneron, Roivant, Sanofi Genzyme, Trevi Therapeutics, Valeant and WebMD. These potential conflicts of interest have been reviewed and managed by Oregon Health & Science University (OHSU). E.S. reports grants from (or served as principal investigator for) AbbVie, Amgen, Arcutis Biotherapeutics, ASLAN Pharmaceuticals, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Hakko Kirin, LEO Pharma, Pfizer, Regeneron, Sanofi and TARGET-DERM. These potential conflicts of interest have been reviewed and managed by OHSU. D.R. has received honoraria as a consultant for AbbVie, Abcuro, AltruBio, Arena, Boehringer-Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Incyte, Janssen, Kyowa Kirin, Eli Lilly and Company, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, UCB and VielaBio; has received research support from AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Dermira, Galderma, Incyte, Janssen, Eli Lilly and Company, Merck, Novartis, Pfizer, and Regeneron Pharmaceuticals; and has served as a paid speaker for AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Incyte, Janssen, Eli Lilly and Company, Novartis, Pfizer, Regeneron Pharmaceuticals and Sanofi. H.E., E.M., C.R.N., Z.L., C.X., E.P. and M.M.-C. are employees of Eli Lilly and Company. E.G.G. is an employee of Almirall S.A. J.I.S. has received grants and/or personal fees from AbbVie, AFYX Therapeutics, Arena Pharmaceuticals, Asana BioSciences, Bluefin, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Luna Pharma, Menlo Therapeutics, Novartis, Pfizer, RAPT Therapeutics, Regeneron and Sanofi., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

The U.S. Food and Drug Administration approval of dupilumab for moderate-to-severe atopic dermatitis shifted the paradigm from use of broad, systemic immunosuppressants to a safer, targeted treatment and led to the emergence of newer interleukin (IL)-4/IL-13 directed biologics and small molecule therapies, namely Janus kinase (JAK) inhibitors (JAKi). Tralokinumab and emerging (not yet approved) lebrikizumab, which both target IL-13, are alternative biologics to dupilumab. The emerging anti-IL-31 receptor nemolizumab is likely to be used second-line to other biologics, primarily for pruritus. Three JAKi are currently in use for treating atopic dermatitis, 2 of which, abrocitinib and upadacitinib, are U.S. Food and Drug Administration-approved. This review provides an in-depth, practical discussion on use of these biologics and JAKi that are approved or have completed phase 3 clinical trials in pediatric patients and adults, comparing the groups of medications based on available efficacy and safety data., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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

Importance: Atopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population., Objective: To assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents., Design, Setting, and Participants: Prespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021., Interventions: Patients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up)., Main Outcomes and Measures: Safety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points)., Results: A total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate., Conclusions and Relevance: In this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile., Trial Registration: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up).

Background: Baricitinib demonstrated efficacy in treating adults with moderate-to-severe atopic dermatitis (AD) in Phase 3 clinical trials., Objective: To examine long-term efficacy of baricitinib combined with topical corticosteroids (TCS) in adult patients from a Phase 3 study, BREEZE-AD7 (NCT03733301), enrolled in ongoing extension study, BREEZE-AD3 (NCT03334435)., Methods: Upon BREEZE-AD7 completion, responders or partial responders (RPR [vIGA-AD™ ≤2]) receiving baricitinib 2-mg or 4-mg + TCS maintained their original treatment doses in BREEZE-AD3. Nonresponders (NR; vIGA-AD 3,4) receiving baricitinib 2-mg were rerandomized 1:1 to baricitinib 2-mg or 4-mg; NR receiving baricitinib 4-mg remained on same dose. Integrated data from all patients (RPR + NR = baricitinib 4-mg intent-to-treat [ITT] cohort) receiving continuous baricitinib 4-mg in BREEZE-AD7 through BREEZE-AD3 were analysed, along with baricitinib 4-mg or 2-mg RPR cohorts. Primary endpoint was proportion of patients with vIGA-AD (0,1) at Weeks 16, 36 and 52 (Weeks 32, 52 and 68 of continuous therapy). Additional outcomes included improvement in EASI75 and Itch NRS (up to Week 32). Missing data were imputed by last observation carried forward., Results: In baricitinib 4-mg ITT cohort (N = 102), proportions of patients achieving vIGA-AD (0,1) at Week 32, Week 52, and Week 68 were 21.6%, 26.5% and 23.5%; EASI75 were 46.1%, 40.2% and 43.1%, respectively. Itch NRS ≥4-point improvement (Itch ≥4) were 47.3% at Week 16 and 40.6% at Week 32. In baricitinib 4-mg RPR cohort (N = 63), proportions of patients achieving vIGA-AD (0,1) at Week 32, Week 52 and Week 68 were 31.7%, 33.3% 34.9%, respectively; EASI75 were 57.1%, 49.2% and 49.2%, respectively. Itch ≥4 were 53.6% at Week 16 and 46.4% at Week 32. Corresponding proportions for baricitinib 2-mg RPR cohort (N = 53) for vIGA-AD (0,1) were 39.6%, 45.3% and 30.2%; EASI75 were 77.4%, 69.8% and 58.5%, respectively. Itch ≥4 were 56.3% at Week 16 and 47.9% at Week 32., Conclusion: Baricitinib 4-mg and 2-mg combined with TCS maintained clinically meaningful sustained efficacy over 68 weeks of continuous treatment., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

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

Background: The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years., Methods: 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls). Long-term follow-up at ages 3, 4 and 5 years was via parental questionnaires. Main outcomes were parental report of a clinical diagnosis of atopic dermatitis and food allergy., Results: Parents reported more frequent moisturizer application in the emollient group through to 5 years. A clinical diagnosis of atopic dermatitis between 12 and 60 months was reported for 188/608 (31%) in the emollient group and 178/631 (28%) in the control group (adjusted relative risk 1.10, 95% confidence interval 0.93 to 1.30). Although more parents in the emollient group reported food reactions in the previous year at 3 and 4 years, cumulative incidence of doctor-diagnosed food allergy by 5 years was similar between groups (92/609 [15%] emollients and 87/632 [14%] controls, adjusted relative risk 1.11, 95% confidence interval 0.84 to 1.45). Findings were similar for cumulative incidence of asthma and hay fever., Conclusions: Daily emollient application during the first year of life does not prevent atopic dermatitis, food allergy, asthma or hay fever., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of the interleukin-4Rα-interleukin-13Rα1 heterodimer receptor signaling complex., Methods: We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator's Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed., Results: In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001). In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001). Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation., Conclusions: In the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis. (Funded by Dermira; ADvocate1 and ADvocate2 ClinicalTrials.gov numbers, NCT04146363 and NCT04178967, respectively.)., (Copyright © 2023 Massachusetts Medical Society.)

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

Background: Baricitinib, an oral, selective Janus kinase 1/2 inhibitor, demonstrated long-term efficacy in moderate-to-severe atopic dermatitis in an ongoing double-blind, phase III, long-term extension study, BREEZE-AD3 (NCT03334435)., Objectives: To evaluate the efficacy and safety of downtitration and treatment withdrawal in a substudy of BREEZE-AD3., Methods: The substudy included patients (N = 526) treated with baricitinib 4 mg or 2 mg at entry into BREEZE-AD3 who achieved a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD®) scale score of 0 (clear), 1 (almost clear) or 2 (mild) at week 52. Patients treated with baricitinib 4 mg were rerandomized to baricitinib 4 mg (continuous dosing), baricitinib 2 mg (downtitration) or placebo (treatment withdrawal, 4-mg cohort), and patients treated with baricitinib 2 mg were rerandomized to baricitinib 2 mg (continuous dosing), baricitinib 1 mg (downtitration), or placebo (treatment withdrawal, 2-mg cohort). After 16 weeks, we assessed the proportion of patients with vIGA-AD® 0/1, vIGA-AD® 0/1/2, vIGA-AD® ≥ 3 (loss of response; criterion to readminister the original baricitinib dose) and for patients who were readministered the original baricitinib dose, we assessed the proportion of patients who recaptured vIGA-AD® 0/1/2 within 16 weeks of treatment readministration (patients in the continuous dosing maintained the same dose)., Results: For the continuous dosing, downtitration, and treatment withdrawal groups 51%, 45% and 30% of patients in the 4-mg cohort achieved vIGA-AD® 0/1 and 87%, 61% and 50% of patients achieved vIGA-AD® 0/1/2, respectively. For the 2-mg cohort, the respective proportions of patients were 48%, 42% and 25% for vIGA-AD® 0/1 and 92%, 71% and 45% for vIGA-AD® 0/1/2. The respective proportions of patients with vIGA-AD® ≥ 3 were 39%, 49% and 56% in the 4-mg cohort and 41%, 41% and 64% in the 2-mg cohort. Of those who were readministered the original baricitinib dose, the proportions of patients who recaptured vIGA-AD® 0/1/2 among the continuous dosing, downtitration, and treatment withdrawal groups were 80%, 85% and 88% in the 4-mg cohort and 90%, 56% and 86% in the 2-mg cohort, respectively., Conclusions: Baricitinib allows flexibility for patients to downtitrate or stop treatment. For patients who downtitrated treatment, the majority maintained efficacy through 16 weeks. Most patients who lost efficacy with downtitration or treatment withdrawal achieved clinically relevant efficacy upon readministration of their original dose., Competing Interests: Conflicts of interest: See Appendix., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Importance: Lebrikizumab (LEB), a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) during 16 weeks of monotherapy in a phase 2b trial, and two 52-week phase 3 trials., Objective: To evaluate efficacy and safety of LEB combined with low- to mid-potency topical corticosteroids (TCS) in patients with moderate-to-severe AD., Design, Setting, and Participants: The ADhere trial was a 16-week randomized, double-blinded, placebo (PBO)-controlled, multicenter, phase 3 clinical trial conducted from February 3, 2020, to September 16, 2021. The study was conducted at 54 outpatient sites across Germany, Poland, Canada, and the US and included adolescent (aged ≥12 to <18 years weighing ≥40 kg) and adult patients with moderate-to-severe AD. The treatment allocation ratio was 2:1 (LEB:PBO)., Interventions: Overall, 211 patients were randomized to subcutaneous LEB (loading dose of 500 mg at baseline and week 2, followed by 250 mg every 2 weeks [Q2W] thereafter) or PBO Q2W in combination with TCS for 16 weeks., Main Outcomes and Measures: Efficacy analyses at week 16 included proportions of patients achieving Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with 2 or more points improvement from baseline, and 75% improvement in the Eczema Area and Severity Index (EASI-75). Key secondary end points included evaluation of itch, itch interference on sleep, and quality of life. Safety assessments included monitoring adverse events (AEs)., Results: The mean (SD) age of patients was 37.2 (19.3) years, 103 (48.8%) patients were women, 31 (14.7%) patients were Asian, and 28 (13.3%) patients were Black/African American. At week 16, IGA (0,1) was achieved by 145 (41.2%) patients in the LEB+TCS group vs 66 (22.1%) receiving PBO+TCS (P = .01); corresponding proportions of patients achieving EASI-75 were 69.5% vs 42.2% (P < .001). The LEB+TCS group showed statistically significant improvements in all key secondary end points. Most treatment-emergent adverse events (TEAEs) were nonserious, mild or moderate in severity, and did not lead to study discontinuation. The TEAEs frequently reported in the LEB+TCS group included conjunctivitis (7 [4.8%]), headache (7 [4.8%]), hypertension (4 [2.8%]), injection site reactions (4 [2.8%]), and herpes infection (5 [3.4%]) vs 1.5% or less patient-reported frequencies in the PBO+TCS group. Similar frequencies of patient-reported serious AEs following LEB+TCS (n = 2, 1.4%) and PBO+TCS (n = 1, 1.5%)., Conclusions and Relevance: In this randomized phase 3 clinical trial, LEB+TCS was associated with improved outcomes in adolescents and adults with moderate-to-severe AD compared with TCS alone, and safety was consistent with previously reported AD trials., Trial Registration: ClinicalTrials.gov Identifier: NCT04250337.

Background: OX40 is crucial for T-cell differentiation and memory induction. The anti-OX40 antibody, rocatinlimab inhibits the OX40 pathway. We evaluated the efficacy and safety of rocatinlimab in adults with moderate-to-severe atopic dermatitis., Methods: This multicentre, double-blind, placebo-controlled phase 2b study was done at 65 secondary and tertiary sites in the USA, Canada, Japan, and Germany. Eligible patients were adults (aged 18 years or older) with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria or local diagnostic criteria) with moderate-to-severe disease activity, as defined by an Eczema Area and Severity Index (EASI) score of 16 or more, validated Investigator's Global Assessment for Atopic Dermatitis score of 3 (moderate) or 4 (severe), and affected body surface area 10% or higher at both screening and baseline, with documented history (within 1 year) of inadequate response to topical medications or if topical treatments were medically inadvisable. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous rocatinlimab every 4 weeks (150 mg or 600 mg) or every 2 weeks (300 mg or 600 mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. Percentage change from baseline in EASI score was assessed as the primary endpoint at week 16 and during the active extension and follow-up in all randomly assigned patients exposed to study drug with a post-baseline EASI score at week 16 or earlier according to the group they were randomly assigned to. Safety was assessed in all randomly assigned patients exposed to study drug; patients were analysed according to the group they were randomly assigned to. The study is registered with ClinicalTrials.gov, NCT03703102., Findings: Between Oct 22, 2018, and Oct 21, 2019, 274 patients (114 [42%] women, 160 [58%] men; mean age 38·0 years [SD 14·5]) were randomly assigned to one of the rocatinlimab groups (217 [79%] patients) or to the placebo group (57 [21%] patients). Compared with placebo (-15·0 [95% CI -28·6 to -1·4]), significant least-squares mean percent reductions in EASI score at week 16 were observed in all rocatinlimab groups (rocatinlimab 150 mg every 4 weeks -48·3 [-62·2 to -34·0], p=0·0003; rocatinlimab 600 mg every 4 weeks -49·7 [-64·3 to -35·2], p=0·0002; rocatinlimab 300 mg every 2 weeks -61·1 [-75·2 to -47·0], p<0·0001; and rocatinlimab 600 mg every 2 weeks -57·4 [-71·3 to -43·4], p<0·0001). The most common adverse events during the double-blind period in patients receiving rocatinlimab (adverse events ≥5% of patients in the total rocatinlimab group and more common than the placebo group) were pyrexia (36 [17%] patients), nasopharyngitis (30 [14%] patients), chills (24 [11%] patients), headache (19 [9%] patients), aphthous ulcer (15 [7%] patients), and nausea (13 [6%] patients). There were no deaths., Interpretation: Patients treated with rocatinlimab had progressive improvements in atopic dermatitis, which was maintained in most patients after treatment discontinuation. Treatment was well tolerated., Funding: Kyowa Kirin., Competing Interests: Declaration of interests EG-Y reports research funds (grants paid to the institution) from Amgen, AnaptysBio, Asana Biosciences, AstraZeneca, Boehringer Ingelheim, Cara Therapeutics, Celgene, Eli Lilly, Innovaderm, Kyowa Kirin, Leo Pharma, Novartis, Pfizer, and Regeneron Pharmaceuticals; served as a consultant for AbbVie, Almirall, Amgen, Arena, Asana Biosciences, Aslan Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol-Meyers Squibb, Cara Therapeutics, Celgene, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Janssen Biotech, Kyowa Kirin, Leo Pharma, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target Pharma Solutions, UCB, and Ventyx Biosciences; reports personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Aslan Pharma, Boston Consulting Group, Collective Acumen, Dermira, Eli Lilly, Evidera, Excerpta Medica, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin Pharmaceutical Development, Leo Pharma, Medscape, Merck, Pfizer, Physicians World, Regeneron, Roivant, Sanofi-Genzyme, Trevi Therapeutics, Valeant, and WebMD; and reports grants from or serves as Principal Investigator for AbbVie, Amgen, Arcutis, Aslan, Castle Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Hakko Kirin, Leo Pharma, Pfizer, Regeneron, Sanofi, and TARGET-DERM. These potential conflicts of interest have been reviewed and managed by Oregon Health & Science University. KR served as an adviser or paid speaker for or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Forward Pharma, Gilead, Galderma, Janssen-Cilag, Kyowa Kirin, Leo Pharma, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, and UCB and is a co-founder of Moonlake Immunotherapeutics. KK reports consulting fees or advisory board honoraria from Japan Tobacco, Kao, Leo Pharma, Chugai Pharmaceutical, Maruho, Pola Pharma, AbbVie, Eli Lilly, Sanofi, and Pfizer; and research grants from Leo Pharma, Japan Tobacco, P&G Japan, Eli Lilly Japan, Tanabe Mitsubishi, Ono Pharmaceutical, Kyowa Kirin, Pola Pharma, AbbVie, Sanofi, Kose, and Kyorin Pharmaceutical. KI reports lecture fees from AbbVie, Lilly, Sanofi, and Maruho. EE is an employee of Kyowa Kirin International. MF is a consultant for P&G Innovation GK. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)