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Background: Atopic dermatitis (AD) is an inflammatory skin disease with significant unmet need. Blockade of the OX40-OX40 ligand (OX40L) costimulation pathway by targeting OX40L on antigen-presenting cells (APCs) with a fully human noncytotoxic, nondepleting anti-OX40L monoclonal antibody (amlitelimab; SAR445229; KY1005) is a novel way to modulate persistent inflammation., Objectives: To assess the safety and efficacy of amlitelimab over 16 weeks in adults with AD in a phase IIa double-blind placebo-controlled study., Methods: The study was conducted at 19 hospitals in Germany, Poland, Spain and the UK. Eligible patients with moderate-to-severe AD were randomized (1 : 1 : 1) to low-dose intravenous (IV) amlitelimab (200 mg), high-dose IV amlitelimab (500 mg) or placebo, followed by three maintenance doses (50% of loading dose) at 4, 8 and 12 weeks, with safety follow-up to week 36. The co-primary endpoints were the incidence of treatment-emergent adverse events (all patients who received ≥ 1 dose of the study drug) and mean percentage change in Eczema Area and Severity Index (EASI) to week 16 (full analysis set)., Results: Between 13 December 2018 and 12 May 2020, 89 patients were randomly assigned to low- (n = 29) or high-dose amlitelimab (n = 30) or placebo (n = 29), of whom 88 proceeded to treatment [37 women (42%), 51 (58%) men; mean (SD) age 33.6 (11.9) years]. Amlitelimab was generally well tolerated with an unremarkable safety profile; no hypersensitivity events were reported. For the primary endpoint, the least square mean percentage change in EASI from baseline to week 16 was -80.12% [95% confidence interval (CI) -95.55 to -64.68; P = 0.009 vs. placebo] and -69.97% (95% CI -85.04 to -54.60; P = 0.07 vs. placebo) for the low- (n = 27) and high-dose (n = 27) amlitelimab groups, respectively, vs. -49.37% (95% CI -66.02 to -32.72) for placebo (n = 24). Numerically greater reductions in EASI were observed for amlitelimab vs. placebo from weeks 2 to 16., Conclusions: Novel targeting of OX40L-expressing APCs with amlitelimab was well tolerated and resulted in clinically meaningful improvements in AD., Competing Interests: Conflicts of interest: S.W. reports research grants (institutional) from AbbVie, Almirall, Eli Lilly, Galderma, LEO Pharma, Pfizer and Sanofi; and consultancy fees from AbbVie, Almirall, Boehringer, Eli Lilly, Galderma, LEO Pharma, Pfizer and Sanofi. T.B. reports consultancy fees from AbbVie, Affibody, Almirall, AnaptysBio, Asana Biosciences, ASLAN Pharmaceuticals, Bayer Health, BioVerSys, Boehringer Ingelheim, Bristol-Myers Squibb, Connect Pharma, Dermavant, DIECE Therapeutics, Domain Therapeutics, EQRx, Galderma, Glenmark, GSK, Incyte, Innovaderm, IQVIA, Janssen, Kirin, Kymab, LEO, LG Chem, Lilly, L’Oréal, MSD, Novartis, Numab, OM-Pharma, Pfizer, Pierre Fabre, Sanofi/Regeneron and UCB. M.J.C. reports research grants (institutional) and consultancy fees from Hyphens Pharma, Johnson & Johnson, Kymab, L’Oréal, Leo Pharma, Perrigo (ACO Nordic), Pfizer, Regeneron and Sanofi Genzyme; and is a board member of the European Academy of Dermatology and Venereology and a voluntary medical advisor to the National Eczema Society, UK. A.R. reports research grants (personal and institutional) from AbbVie, Alvotech, Amgen, AnaptysBio, Argenx, AstraZeneca, Biothera, BMS, Celgene, Celltrion, Dermira, Galderma, Inflarx, Janssen, Kiniksa, Kymab, Leo Pharma, Novartis, Pfizer, Trevi Therapeutics and UCB; and consultancy fees from AbbVie, Chema Rzeszow, Eli Lilly, Galderma, Leo Pharma, Novartis, Sandoz, Sanofi-Aventis and Takeda. B.P.-B. was an employee of Sanofi and Sanofi stockholder during the development of this manuscript. N.B. is a former employee and shareholder in Kymab Ltd. S.G. is a former employee of Kymab Ltd and a Sanofi stockholder. S.Q. is a former employee of Kymab Ltd. M.S. is a former employee of Sanofi. R.W. has received consultancy fees from Kymab Ltd. J.T.O’M. is an employee of Sanofi and may hold stock and/or stock options in the company., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis., Methods: This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434., Findings: Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation., Interpretation: Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults., Funding: Sanofi and Regeneron Pharmaceuticals., Competing Interests: Declaration of interests ASP has been an investigator for AbbVie, AnaptysBio, Dermavant, Eli Lilly, Incyte, Janssen, Krystal Biotech, LEO Pharma, Regeneron Pharmaceuticals, and UCB; a consultant with honorarium for AbbVie, Acrotech, Almirall, Amgen, Amryt Pharma, Arcutis Antiobix, Arena Pharmaceuticals, Azitra, BioCryst, BiomX, Boehringer Ingelheim, Botanix, BridgeBio, Bristol Myers Squibb, Castle Creek Biosciences, Catawba Research, Eli Lilly, Exicure, Gilead, Incyte, Janssen, Johnson & Johnson, Kamari Pharma, LEO Pharma, Novartis, OM Pharma, Pfizer, Pierre Fabre Dermo-Cosmetics, RAPT Therapeutics, Regeneron Pharmaceuticals, Sanofi, Seanergy, UCB, and Union; and on the data and safety monitoring board for AbbVie, Abeona, Bausch, Galderma, and Novan. ELS has been an investigator for AbbVie, Eli Lilly, Incyte, Kyowa Hakko Kirin, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics; received consultant fees from AbbVie, Amgen, Arena Pharmaceuticals, Aslan Pharma, Benevolent AI Bio Limited, BiomX, Bluefin Biomedicine, Boehringer Ingelheim, Boston Consulting Group, Collective Acumen, Coronado, Corevita, Dermavant, Eli Lilly, Evidera, ExcerptaMedica, Forté Bio RX, Galderma, GSK, Incyte, Janssen, Kyowa Hakko Kirin, LEO Pharma, Menlo Therapeutics, Merck, Novartis, Pfizer, Pierre Fabre Dermo-Cosmetics, Regeneron Pharmaceuticals, Roivant, Sanofi, SPARC India, Trevi Therapeutics, and Valeant; received study grants from AbbVie, Amgen, Arcutis, Aslan Pharma, Corevita, Eli Lilly, Incyte, Kyowa Hakko Kirin, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics; served as a speaker for Eli Lilly, Incyte, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, and Sanofi; and served on advisory boards for Arena Pharmaceuticals, Eli Lilly, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, and Sanofi. ECS has been a consultant for AbbVie, Dermavant, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, and Verrica Pharmaceuticals; on the data and safety monitoring board for GSK, LEO Pharma, Novan, Pfizer, and USB; served on advisory boards for Sanofi; and a principal investigator in clinical trials for Eli Lilly, Regeneron Pharmaceuticals, and Verrica Pharmaceuticals. MJC has been an investigator and consultant for Astellas, Galapagos, Hyphens Pharma, Johnson & Johnson, LEO Pharma, L’Oréal, Novartis, Oxagen, Pfizer, Reckitt Benckiser, Regeneron Pharmaceuticals, and Sanofi; and a consultant for AbbVie, Almirall, Anacor Pharmaceuticals, Boots, Dermavent, Galderma, Menlo Therapeutics, and Proctor & Gamble; and received research grants from Hyphens Pharma, Johnson & Johnson, LEO Pharma, L’Oréal, Pfizer, Regeneron Pharmaceuticals, and Sanofi. AW has been an investigator for Beiersdorf, Eli Lilly, Galderma, LEO Pharma, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi; a consultant for AbbVie, Almirall, Anacor Pharmaceuticals, Eli Lilly, Galapagos, Galderma, LEO Pharma, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi; and received research grants from Beiersdorf, LEO Pharma, and Pierre Fabre. PDA has been an investigator for Regeneron Pharmaceuticals; and received a research grant and been an advisor for Sanofi. WS has been a speaker, advisory board member, and investigator for AbbVie, Amgen, AstraZeneca, GSK, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, and Sanofi; a consultant for AbbVie, LEO Pharma, and Regeneron Pharmaceuticals; received investigator grants from AbbVie, Aimmune Therapeutics, Genentech, GSK, Incyte, LEO Pharma, Novartis, Pfizer, Teva, and Vanda Pharmaceuticals; a speaker for Teva; and an advisor for Genentech. MEG has been an investigator for AbbVie, Arcutis Biotherapeutics, Dermira, Dermavant, Eli Lilly, Incyte, Krystal Biotech, Regeneron Pharmaceuticals, Sun Pharma, and Verrica Pharmaceuticals; a speaker for Galderma, Pfizer, Primus Pharmaceuticals, Regeneron Pharmaceuticals, and Sanofi; and a consultant for Unilever and Verrica Pharmaceuticals. LCS has been an investigator for DBV Technologies and Regeneron Pharmaceuticals; received research support from Genentech; and has been a consultant for AbbVie, Alladapt Immunotherapeutics, LEO Pharma, Regeneron Pharmaceuticals, and Sanofi. RS has been an investigator for Galderma, Regeneron Pharmaceuticals, and UCB; an advisory board member for LEO Pharma and Pfizer; and speaker for Beiersdorf. BL has been an investigator for Castle, Dermira, Franklin Biosciences, and Pfizer; an investigator, speaker, and consultant for AbbVie, Dermtech, Eli Lilly, Incyte, LEO Pharma, Regeneron Pharmaceuticals, and UCB; an investigator and consultant for Strata; and a speaker and consultant for Dermavant and Sanofi. SM has been an investigator for AstraZeneca, Pfizer, and Regeneron Pharmaceuticals. ZW, YS, BA, MD, MPK, MAK, DMW, GDY, and AB are employees and shareholders of Regeneron Pharmaceuticals. LPM, EL, NP, AD-B, and JTO are employees of and may hold stock or stock options in Sanofi. NA is a former employee and shareholder of Regeneron Pharmaceuticals., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Moderate-to-severe atopic dermatitis (AD) often requires long-term management with systemic therapies., Objective: Our objective was to report the safety and efficacy of dupilumab treatment up to 4 years in adults with moderate-to-severe AD and efficacy in a subgroup of patients who transitioned from dupilumab once-weekly (qw) to administration every other week (q2w)., Methods: This interim analysis of the open-label extension study (NCT01949311) evaluated dupilumab 300 mg qw or q2w in adults previously enrolled in dupilumab trials for moderate-to-severe AD. Patients switched from qw to q2w following protocol amendment. The primary outcome was safety; efficacy was also assessed., Results: Of 2677 patients enrolled and treated, 352 (13.1%) completed week 204 (end of efficacy assessments) and 202 (7.5%) completed safety follow-up through week 244. Self-reported compliance was 98.1%. Dupilumab's safety profile was consistent with previous reports. Common treatment-emergent adverse events (≥5%) included nasopharyngitis, AD, upper respiratory tract infection, oral herpes, conjunctivitis, injection-site reaction, and headache. At week 204, mean ± standard deviation (SD) Eczema Area and Severity Index was 2.46 ± 3.98, and mean percent change from parent study baseline (PSBL) was -91.07%; mean ± SD Pruritus Numerical Rating Scale score was 2.10 ± 1.83, and mean percent change from PSBL was -68.74%. Efficacy was maintained in patients (n = 226) who transitioned from qw to q2w dosing. Limitations of this study included its open-label design, the lack of control arm, and smaller subsets of patients at later timepoints and receiving the approved q2w regimen., Conclusion: These results support dupilumab as continuous long-term treatment for adults with moderate-to-severe AD; efficacy was sustained following transition from qw to q2w dosing. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT01949311., (© 2022. The Author(s).)

Background: For adolescent patients (aged ≥ 12 to < 18 years) with uncontrolled moderate-to-severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile. However, long-term data on the approved dose regimens of dupilumab in adolescents with AD are lacking., Objectives: This open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate-to-severe AD who had participated in dupilumab parent trials., Methods: Patients enrolled under the original study protocol received subcutaneous dupilumab according to a weight-based regimen (2 or 4 mg/kg every week). Following protocol amendment, patients were switched to subcutaneous dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, and newly enrolled patients were started on dupilumab 300 mg q4w. Patients with an inadequate clinical response (Investigator's Global Assessment [IGA] score of 0/1 was not reached) to the q4w regimen could be uptitrated to the approved dupilumab dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively). Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required., Results: Data for 294 patients (mean age 14.7 years) were analyzed, 102 (34.7%) of whom had completed the 52-week visit at the database lock. The dupilumab long-term safety profile was comparable to that seen in adults and consistent with the known safety profile. Most treatment-emergent adverse events were mild/moderate. By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in Eczema Area and Severity Index (EASI). Most (70.9%) patients required uptitration to the approved dupilumab dose regimen. The proportions of uptitrated patients with an IGA score of 0/1 or 75% improvement in EASI increased over time, reaching 35.7% and 51.9%, respectively, 48 weeks after the first uptitration visit. By week 52, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication; 56.7% relapsed and were subsequently re-initiated on treatment, with a mean time to re-initiation of 17.5 (± standard deviation 17.3) weeks., Conclusions: Consistent with results seen with short-term treatment, long-term treatment with dupilumab showed an acceptable safety profile while providing incremental clinical benefit with continued treatment over time. The high proportion of patients who needed uptitration because of inadequate response to q4w dosing supports the q2w dose regimen as optimal for this age group. Finally, the majority of patients who stopped medication after having clear/almost clear skin sustained over 12 weeks experienced disease recurrence, suggesting the need for continued dupilumab dosing to maintain efficacy., Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454, NCT02407756, NCT03054428, and NCT03050151., Infographic: Video abstract: What is the long-term safety and efficacy profile in adolescents with moderate-to-severe atopic dermatitis treated with the approved dupilumab dose regimen? (MP4 40,966 KB)., (© 2022. The Author(s).)

Background: Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD)., Objectives: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD., Methods: In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0-1 and a reduction from baseline of ≥ 2 points at week 16., Results: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37-32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75-55·97; P < 0·001) and had ≥ 3-point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26-55·34; P < 0·001) and ≥ 4-point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69-45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment-emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group., Conclusions: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile., (© 2021 Sanofi. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Previous studies of dupilumab in adolescents and adults with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful adverse changes in laboratory parameters., Objective: The aim of this study was to assess laboratory outcomes in children aged 6-11 years with severe AD in a randomized, placebo-controlled, phase III trial of dupilumab., Methods: Children aged 6-11 years with severe AD were randomized 1:1:1 to 16 weeks of dupilumab 300 mg every 4 weeks, 100 or 200 mg every 2 weeks, or matching placebo, all with concomitant topical corticosteroids (TCS). Blood samples were collected at baseline and Weeks 4, 8, and 16; urine samples were collected at baseline and Weeks 4 and 16., Results: Of 367 patients enrolled in the study, 362 were included in the safety analysis, 351 completed study treatment, and 4 withdrew due to treatment-emergent adverse events not related to laboratory abnormalities. Both dupilumab + TCS groups showed overall trends toward increases in mean blood levels of eosinophils and alkaline phosphatase, and decreases in mean blood levels of platelets, neutrophils, and lactate dehydrogenase levels, without corresponding mean changes in the placebo + TCS group. None of these changes were associated with symptoms or clinically meaningful adverse outcomes, and none led to treatment modification. No clinically significant changes or trends were observed for other measured laboratory parameters., Conclusion: There were no clinically meaningful adverse changes in routine laboratory parameters attributable to treatment with dupilumab + TCS. Changes in platelet counts and lactate dehydrogenase levels likely reflect reduced inflammation. These results confirm similar findings in adults and adolescents, and suggest that there is no need for routine laboratory monitoring of children aged 6-11 years treated with dupilumab + TCS for severe AD., Trial Registration: ClinicalTrials.gov Identifier: NCT03345914. Does treatment with dupilumab require routine laboratory monitoring in 6- to 11-year-old children with severe atopic dermatitis? (MP4 180482 kb)., (© 2021. The Author(s).)

Background: Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16-week, randomized, placebo-controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4/IL-13 signalling, significantly improved signs and symptoms with acceptable safety; longer-term safety and efficacy data are lacking., Objectives: To report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD., Methods: Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study and subsequent open-label extension (OLE) study. Patients received single-dose dupilumab 2 or 4 mg kg -1 followed by 8-week pharmacokinetic sampling, then 2 or 4 mg kg -1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration-time profile and treatment-emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP-NRS) score., Results: Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target-mediated pharmacokinetics characterized dupilumab concentrations (week 24-48 mean serum concentrations: 2 mg kg -1 , 61-77 mg L -1 ; 4 mg kg -1 , 143-181 mg L -1 ). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg -1 , 47%; 4 mg kg -1 , 56%) and AD exacerbation (29% and 13%, respectively). Single-dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP-NRS improved by -37%/-33% and -17%/-20% at week 2 (phase IIa) and -92%/-84% and -70%/-58% at week 52 (OLE), respectively., Conclusions: These safety and efficacy results support the use of dupilumab as a continuous long-term treatment for children aged ≥ 6 to < 12 years with severe AD., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

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