{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:12:44Z","timestamp":1788502364154,"version":"build-2803163510"},"reference-count":37,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"unspecified","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Beijing Research Ward Excellence Program","award":["BRWEP2024W102090109"],"award-info":[{"award-number":["BRWEP2024W102090109"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,8,5]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Treatment responses to systemic therapies for atopic dermatitis (AD) may vary significantly based on medication types, treatment duration, concomitant topical corticosteroid use and specific patient subgroups. Evidence regarding the optimal medication selection and predictors of treatment response is warranted. A systematic approach to studying the effectiveness of systemic treatments from multiple perspectives may generate previously unreported evidence. We aim to quantitatively evaluate the time-course and effectiveness of various systemic treatments for AD, and to identify associated factors that significantly affect their effectiveness, using a pharmacodynamic model-based meta-analysis (MBMA). This protocol describes the methods for this analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Data for the analysis will mainly originate from the database of a living network meta-analysis. We will include randomised controlled trials examining systemic treatments against placebo or any active comparator in patients with moderate-to-severe AD. The Investigator Global Assessment Scale, the Eczema Area and Severity Index Scale, the Patient Oriented Eczema Measure Scale and scales measuring quality of life or itch will be used as outcome measures. Study screening, data extraction and quality assessment will be conducted by two investigators independently. Where available, we will extract efficacy outcome data at each follow-up time point. We will use MBMA, the core principle of which involves developing a pharmacodynamic model to synthesise these longitudinal trial-level data. Whenever possible, modelling and simulation will be conducted for both binary and continuous outcomes. This MBMA will be performed using hierarchical models with non-linear mixed-effects methods including structural, random-effects and covariate models with the maximum likelihood estimation method. Response to systemic treatments will be analysed by conducting 1000 Monte Carlo simulations. Potential influencing factors will be tested using covariate modelling and subgroup analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval is not required for this study. Results from our analyses will be published in a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD420251068535<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-107232","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:10:16Z","timestamp":1788441016000},"page":"e107232","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative evaluations of time-course and effectiveness of systemic treatments for atopic dermatitis: protocol for a pharmacodynamic model-based meta-analysis"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2631-924X","authenticated-orcid":false,"given":"Huan","family":"He","sequence":"first","affiliation":[{"name":"Clinical Research Center, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boran","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zigang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Guo","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing, China"},{"name":"Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"2026090322300939000_16.9.e107232.1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0140-6736(20)31286-1","article-title":"Atopic dermatitis","volume":"396","author":"Langan","year":"2020","journal-title":"Lancet"},{"key":"2026090322300939000_16.9.e107232.2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-018-0001-z","article-title":"Atopic dermatitis","volume":"4","author":"Weidinger","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"2026090322300939000_16.9.e107232.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2007.02679.x"},{"key":"2026090322300939000_16.9.e107232.4","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14167"},{"key":"2026090322300939000_16.9.e107232.5","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.clindermatol.2018.05.007","article-title":"Epidemiology of adult atopic dermatitis","volume":"36","author":"Sacotte","year":"2018","journal-title":"Clin Dermatol"},{"key":"2026090322300939000_16.9.e107232.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2006.00187.x"},{"key":"2026090322300939000_16.9.e107232.7","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.anai.2018.07.006","article-title":"Patient burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study","volume":"121","author":"Silverberg","year":"2018","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2026090322300939000_16.9.e107232.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.07.012"},{"key":"2026090322300939000_16.9.e107232.9","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.19580"},{"key":"2026090322300939000_16.9.e107232.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2023.08.102"},{"key":"2026090322300939000_16.9.e107232.11","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s40265-017-0768-3","article-title":"Dupilumab: First Global Approval","volume":"77","author":"Shirley","year":"2017","journal-title":"Drugs"},{"key":"2026090322300939000_16.9.e107232.12","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1007\/s40265-021-01583-1","article-title":"Tralokinumab: First Approval","volume":"81","author":"Duggan","year":"2021","journal-title":"Drugs"},{"key":"2026090322300939000_16.9.e107232.13","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/s40265-022-01741-z","article-title":"Nemolizumab: First Approval","volume":"82","author":"Keam","year":"2022","journal-title":"Drugs"},{"key":"2026090322300939000_16.9.e107232.14","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s40265-024-02000-z","article-title":"Lebrikizumab: First Approval","volume":"84","author":"Keam","year":"2024","journal-title":"Drugs"},{"key":"2026090322300939000_16.9.e107232.15","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s40265-025-02151-7","article-title":"Stapokibart: First Approval","volume":"85","author":"Shirley","year":"2025","journal-title":"Drugs"},{"key":"2026090322300939000_16.9.e107232.16","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1007\/s40265-021-01638-3","article-title":"Abrocitinib: First Approval","volume":"81","author":"Deeks","year":"2021","journal-title":"Drugs"},{"key":"2026090322300939000_16.9.e107232.17","doi-asserted-by":"publisher","DOI":"10.3310\/PLRQ4216"},{"key":"2026090322300939000_16.9.e107232.18","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1111\/jdv.18345","article-title":"European guideline (EuroGuiDerm) on atopic eczema: part I \u2013 systemic therapy","volume":"36","author":"Wollenberg","year":"2022","journal-title":"Acad Dermatol Venereol"},{"key":"2026090322300939000_16.9.e107232.19","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1001\/jamadermatol.2024.2192","article-title":"Systemic Immunomodulatory Treatments for Atopic Dermatitis: Living Systematic Review and Network Meta-Analysis Update","volume":"160","author":"Drucker","year":"2024","journal-title":"JAMA Dermatol"},{"key":"2026090322300939000_16.9.e107232.20","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12041"},{"key":"2026090322300939000_16.9.e107232.21","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2023-107625"},{"key":"2026090322300939000_16.9.e107232.22","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/cpt.732","article-title":"Quantitative Evaluations of Time-Course and Treatment Effects of Systemic Agents for Psoriasis: A Model-Based Meta-Analysis","volume":"102","author":"Checchio","year":"2017","journal-title":"Clin Pharmacol Ther"},{"key":"2026090322300939000_16.9.e107232.23","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1097\/JS9.0000000000000337","article-title":"A model-based quantitative analysis of efficacy and associated factors of platelet rich plasma treatment for osteoarthritis","volume":"109","author":"Cao","year":"2023","journal-title":"Int J Surg"},{"key":"2026090322300939000_16.9.e107232.24","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.joca.2025.01.008","article-title":"Quantitative analysis of the efficacy and associated factors of intra-articular hyaluronic acid with respect to osteoarthritis symptoms: A systematic review of randomized trials and model-based meta-analysis","volume":"33","author":"Cao","year":"2025","journal-title":"Osteoarthr Cartil"},{"key":"2026090322300939000_16.9.e107232.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00266-6"},{"key":"2026090322300939000_16.9.e107232.26","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1001\/jamadermatol.2020.0796","article-title":"Systemic Immunomodulatory Treatments for Patients With Atopic Dermatitis: A Systematic Review and Network Meta-analysis","volume":"156","author":"Drucker","year":"2020","journal-title":"JAMA Dermatol"},{"key":"2026090322300939000_16.9.e107232.27","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1001\/jamadermatol.2022.0455","article-title":"Systemic Immunomodulatory Treatments for Atopic Dermatitis: Update of a Living Systematic Review and Network Meta-analysis","volume":"158","author":"Drucker","year":"2022","journal-title":"JAMA Dermatol"},{"key":"2026090322300939000_16.9.e107232.28","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1093\/bjd\/ljad393","article-title":"Comparing binary efficacy outcomes for systemic immunomodulatory treatments for atopic dermatitis in a living systematic review and network meta-analysis","volume":"190","author":"Drucker","year":"2024","journal-title":"Br J Dermatol"},{"key":"2026090322300939000_16.9.e107232.29","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1093\/bjd\/ljaf166","article-title":"Living network meta-analysis to compare nemolizumab against other available targeted systemic treatments for atopic dermatitis","volume":"193","author":"Drucker","year":"2025","journal-title":"Br J Dermatol"},{"key":"2026090322300939000_16.9.e107232.30","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"2026090322300939000_16.9.e107232.31","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2022.35060","article-title":"Placebo Response to Oral Administration in Osteoarthritis Clinical Trials and Its Associated Factors: A Model-Based Meta-analysis","volume":"5","author":"Wen","year":"2022","journal-title":"JAMA Netw Open"},{"key":"2026090322300939000_16.9.e107232.32","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1002\/cpt.1305","article-title":"Model-Based Meta-Analysis in Ankylosing Spondylitis: A Quantitative Comparison of Biologics and Small Targeted Molecules","volume":"105","author":"Wu","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"2026090322300939000_16.9.e107232.33","doi-asserted-by":"crossref","DOI":"10.1186\/s13195-020-00630-5","article-title":"Testing whether the progression of Alzheimer\u2019s disease changes with the year of publication, additional design, and geographical area: a modeling analysis of literature aggregate data","volume":"12","author":"Zhang","year":"2020","journal-title":"Alzheimers Res Ther"},{"key":"2026090322300939000_16.9.e107232.34","doi-asserted-by":"crossref","DOI":"10.1093\/sleep\/zsz286","article-title":"Quantitative analysis of the placebo response in pharmacotherapy of insomnia and its application in clinical trials","volume":"43","author":"Zheng","year":"2020","journal-title":"Sleep"},{"key":"2026090322300939000_16.9.e107232.35","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1111\/all.16009","article-title":"Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs","volume":"79","author":"M\u00fcller","year":"2024","journal-title":"Allergy"},{"key":"2026090322300939000_16.9.e107232.36","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1007\/s40265-024-02095-4","article-title":"Emerging Biologic Therapies for the Treatment of Atopic Dermatitis","volume":"84","author":"Alvarenga","year":"2024","journal-title":"Drugs"},{"key":"2026090322300939000_16.9.e107232.37","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.586827","article-title":"Model-Based Meta-Analysis in Psoriasis: A Quantitative Comparison of Biologics and Small Targeted Molecules","volume":"12","author":"He","year":"2021","journal-title":"Front Pharmacol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-107232","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:30:19Z","timestamp":1788499819000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-107232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,2]]},"published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1136\/bmjopen-2025-107232"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-107232","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]}}}