{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:35:35Z","timestamp":1788352535946,"version":"build-2803163510"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005270","name":"Fujian Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2021J05155"],"award-info":[{"award-number":["2021J05155"]}],"id":[{"id":"10.13039\/501100005270","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019595","name":"Youth and Middle-aged Scientific and Technological Innovation Leading Talents Program of the Corps","doi-asserted-by":"publisher","award":["2021GGA030"],"award-info":[{"award-number":["2021GGA030"]}],"id":[{"id":"10.13039\/501100019595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","award":["2021Y9140"],"award-info":[{"award-number":["2021Y9140"]}],"id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To evaluate the utility of therapeutic drug monitoring (TDM) in adalimumab-treated noninfectious uveitis (NIU) patients and determine the prevalence, incidence, and risk factors for anti-adalimumab antibody (AAA) development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective cohort study, the frequency of AAA development, the association between serum drug concentrations and clinical efficacy, and the clinical utility of TDM were evaluated in NIU patients treated with adalimumab (ADA). Eligible patients were divided into a TDM group, in which serum ADA and AAA levels were measured prior to dosing and the treatment regimens were adjusted accordingly, and a control group, in which management was based on clinical judgement. Treatment responses were systematically assessed in both groups throughout the follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We established a therapeutic trough concentration window of 2.9\u20135.8\u00a0\u00b5g\/mL for ADA in NIU patients, with serum trough levels exceeding 8\u00a0\u00b5g\/mL suggesting a potential \u201cceiling effect.\u201d Overall, patients managed with TDM achieved significantly better clinical outcomes than those without TDM: the median time to inflammation remission was shorter (28 days vs. 42 days), the recurrence rate was lower (15% vs. 42%), and the incidence of adverse events was reduced (10% vs. 31%). TDM guidance was implemented for 20 patients (51.3%), with the remaining 19 (48.7%) serving as controls without TDM guidance. Among the 20 patients managed with TDM guidance, six patients (30.0%) who demonstrated inadequate clinical response to adalimumab after at least six months of therapy were classified as nonresponders. Anti-adalimumab antibodies (AAAs) were detected in 3 patients among the nonresponders, with a median concentration of 1041 ng\/mL (range: 578.1\u20131844.3 ng\/mL). These patients presented significantly lower adalimumab trough concentrations (median: 0.55\u00a0\u00b5g\/mL) than AAA-negative patients (median: 3.43\u00a0\u00b5g\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). After TDM guidance, the median adalimumab concentration in nonresponders increased to 1.22\u00a0\u00b5g\/mL, whereas the AAA concentration decreased to 894 ng\/mL (range: 0\u20131197.8 ng\/mL). Concurrently, nonresponders demonstrated measurable improvements in key clinical outcomes, including best-corrected visual acuity, central macular thickness, and standardized ocular inflammation grading scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TDM of adalimumab using practical serum sampling protocols is clinically feasible and has potential benefits for patient management. AAAs were detected in 50% of nonresponders and were associated with lower concentrations of adalimumab. This study provides the first protocolized evidence for TDM implementation for NIU, addressing a critical gap in current uveitis management guidelines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-025-07352-y","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T08:24:13Z","timestamp":1762417453000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunogenicity of adalimumab in patients with noninfectious uveitis based on therapeutic drug monitoring"],"prefix":"10.1186","volume":"23","author":[{"given":"Jing-Wen","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6885-9864","authenticated-orcid":false,"given":"Xuling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"issue":"1","key":"7352_CR1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1080\/09273948.2016.1196713","volume":"26","author":"T Tsirouki","year":"2018","unstructured":"Tsirouki T, Dastiridou A, Symeonidis C, Tounakaki O, Brazitikou I, Kalogeropoulos C, et al. A focus on the epidemiology of uveitis. Ocul Immunol Inflamm. 2018;26(1):2\u201316.","journal-title":"Ocul Immunol Inflamm"},{"issue":"1","key":"7352_CR2","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41433-018-0223-z","volume":"33","author":"YR Hsu","year":"2019","unstructured":"Hsu YR, Huang JC, Tao Y, Kaburaki T, Lee CS, Lin TC, et al. Noninfectious uveitis in the Asia\u2013Pacific region. Eye. 2019;33(1):66\u201377.","journal-title":"Eye"},{"issue":"Suppl 1","key":"7352_CR3","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.3109\/09273948.2016.1158279","volume":"25","author":"F Gao","year":"2017","unstructured":"Gao F, Zhao C, Cheng G, Pei M, Liu X, Wang M, et al. Clinical patterns of uveitis in a tertiary center in North China. Ocul Immunol Inflamm. 2017;25(Suppl 1):S1\u20137.","journal-title":"Ocul Immunol Inflamm"},{"key":"7352_CR4","unstructured":"Proti\u0107 C. Povezanost Gena Razreda I i II Sustava HLA s Upalnim bolestima oka. Diss. University of split. University of Split, Faculty of Health Sciences; 2025."},{"issue":"3","key":"7352_CR5","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1080\/14728214.2019.1663823","volume":"24","author":"U Pleyer","year":"2019","unstructured":"Pleyer U, Pohlmann D, Karde\u015f E, Poddubnyy D, Rademacher J. Emerging drugs for the treatment of noninfectious uveitis. Expert Opin Emerg Drugs. 2019;24(3):173\u201390.","journal-title":"Expert Opin Emerg Drugs"},{"issue":"5","key":"7352_CR6","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.ophtha.2017.11.017","volume":"125","author":"AD Dick","year":"2018","unstructured":"Dick AD, Rosenbaum JT, Al-Dhibi HA, Belfort R Jr, Br\u00e9zin AP, Chee SP, et al. Guidance on noncorticosteroid systemic Immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (FOCUS) initiative. Ophthalmology. 2018;125(5):757\u201373.","journal-title":"Ophthalmology"},{"key":"7352_CR7","unstructured":"Overview. | Adalimumab and dexamethasone for treating non-infectious uveitis | Guidance | NICE. https:\/\/www.nice.org.uk\/guidance\/ta460"},{"key":"7352_CR8","unstructured":"Nation Medical Products Administration. (2020). https:\/\/www.nmpa.gov.cn\/"},{"issue":"1","key":"7352_CR9","doi-asserted-by":"publisher","first-page":"e0297201","DOI":"10.1371\/journal.pone.0297201","volume":"19","author":"M Tomita","year":"2024","unstructured":"Tomita M, Tagami M, Misawa N, Sakai A, Haruna Y, Honda S. Relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis. PLoS ONE. 2024;19(1):e0297201.","journal-title":"PLoS ONE"},{"key":"7352_CR10","doi-asserted-by":"publisher","first-page":"753955","DOI":"10.3389\/fnut.2021.753955","volume":"8","author":"J Li","year":"2021","unstructured":"Li J, Du L, He JN, Chu KO, Guo CL, Wong MOM, et al. Anti-inflammatory effects of GTE in eye diseases[J]. Front Nutr. 2021;8:753955.","journal-title":"Front Nutr"},{"key":"7352_CR11","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s10792-011-9430-3","volume":"31","author":"P Neri","year":"2011","unstructured":"Neri P, Zucchi M, Allegri P, Lettieri M, Mariotti C, Giovannini A. Adalimumab (Humira\u2122): a promising monoclonal anti-tumor necrosis factor alpha in ophthalmology. Int Ophthalmol. 2011;31:165\u201373.","journal-title":"Int Ophthalmol"},{"issue":"6","key":"7352_CR12","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/j.ophtha.2019.11.024","volume":"127","author":"V Lloren\u00e7","year":"2020","unstructured":"Lloren\u00e7 V, Cordero-Coma M, Blanco-Esteban A, Heras-Mulero H, Losada-Castillo MJ, Jovani-Casano V, et al. Drug retention rate and causes of discontinuation of adalimumab in uveitis: real-world data from the biotherapies in uveitis (Bio\u00davea) study group. Ophthalmology. 2020;127(6):814\u201325.","journal-title":"Ophthalmology"},{"issue":"8","key":"7352_CR13","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1080\/09273948.2023.2256850","volume":"32","author":"DI Pach\u00f3n-Su\u00e1rez","year":"2024","unstructured":"Pach\u00f3n-Su\u00e1rez DI, Z\u00e1rate-Pinz\u00f3n L, Cifuentes-Gonz\u00e1lez C, Rojas-Carabali W, Mej\u00eda-Salgado G, Pineda JS, et al. Immunogenicity of adalimumab in patients with Non-Infectious uveitis: systematic review and Meta-Analysis. Ocul Immunol Inflamm. 2024;32(8):1539\u201348.","journal-title":"Ocul Immunol Inflamm"},{"key":"7352_CR14","doi-asserted-by":"crossref","unstructured":"Liau MM, Oon HH. Therapeutic drug monitoring of biologics in psoriasis. Biol Targets Ther. 2019;(13):127\u201332.","DOI":"10.2147\/BTT.S188286"},{"issue":"10","key":"7352_CR15","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1136\/bjophthalmol-2021-319072","volume":"106","author":"L Sejournet","year":"2022","unstructured":"Sejournet L, Kerever S, Mathis T, Kodjikian L, Jamilloux Y, Seve P. Therapeutic drug monitoring guides the management of patients with chronic non-infectious uveitis treated with adalimumab: a retrospective study. Br J Ophthalmol. 2022;106(10):1380\u20136.","journal-title":"Br J Ophthalmol"},{"issue":"2","key":"7352_CR16","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1093\/ibd\/izaa073","volume":"27","author":"J Yao","year":"2021","unstructured":"Yao J, Jiang X, You JH. A systematic review on cost-effectiveness analyses of therapeutic drug monitoring for patients with inflammatory bowel disease: from immunosuppressive to anti-TNF therapy. Inflamm Bowel Dis. 2021;27(2):275\u201382.","journal-title":"Inflamm Bowel Dis"},{"issue":"7\u20138","key":"7352_CR17","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1080\/09273948.2021.1936565","volume":"30","author":"KM McKay","year":"2022","unstructured":"McKay KM, Apostolopoulos N, Chou B, Leveque TK, Van Gelder RN. Anti-adalimumab antibodies in patients with non-infectious ocular inflammatory disease: a case series. Ocul Immunol Inflamm. 2022;30(7\u20138):1721\u20135.","journal-title":"Ocul Immunol Inflamm"},{"key":"7352_CR18","doi-asserted-by":"crossref","unstructured":"Urquiaga M, Saag KG. Risk for osteoporosis and fracture with glucocorticoids. Best Pract Res Clin Rheumatol. 2022;36(3):101793.","DOI":"10.1016\/j.berh.2022.101793"},{"key":"7352_CR19","doi-asserted-by":"crossref","unstructured":"Nowak KM, Rdzanek-Pikus M, Romanowska-Pr\u00f3chnicka K, Nowakowska-P\u0142aza A, Papierska L. High prevalence of steroid-induced glucose intolerance with normal fasting glycaemia during low-dose glucocorticoid therapy: an oral glucose tolerance test screening study. Rheumatology. 2021;60(6):2842\u201351.","DOI":"10.1093\/rheumatology\/keaa724"},{"issue":"1","key":"7352_CR20","first-page":"1623847","volume":"2019","author":"A Bitossi","year":"2019","unstructured":"Bitossi A, Bettiol A, Silvestri E, Di Scala G, Bacherini D, Lopalco G, et al. Adalimumab accounts for Long-Term control of noninfectious uveitis also in the absence of concomitant DMARD treatment: A multicenter retrospective Study[J]. Mediat Inflamm. 2019;2019(1):1623847.","journal-title":"Mediat Inflamm"},{"key":"7352_CR21","doi-asserted-by":"crossref","unstructured":"Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. American journal of ophthalmology. 2005;140(3):509\u2009\u2013\u200916.","DOI":"10.1016\/j.ajo.2005.03.057"},{"issue":"4","key":"7352_CR22","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/S0161-6420(85)34001-0","volume":"92","author":"RB Nussenblatt","year":"1985","unstructured":"Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardizatlon of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985;92(4):467\u201371.","journal-title":"Ophthalmology"},{"issue":"1","key":"7352_CR23","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12348-022-00307-0","volume":"12","author":"GJ Jaffe","year":"2022","unstructured":"Jaffe GJ, Carlos E. Pavesio. Recurrence rates in ocular non-infectious uveitis according to US FDA criteria or rest of world criteria. J Ophthalmic Inflamm Infect. 2022;12(1):30.","journal-title":"J Ophthalmic Inflamm Infect"},{"issue":"12","key":"7352_CR24","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.1016\/j.ophtha.2016.08.025","volume":"123","author":"M Cordero-Coma","year":"2016","unstructured":"Cordero-Coma M, Calleja-Antol\u00edn S, Garzo-Garc\u00eda I, Nu\u00f1ez-Garn\u00e9s AM, \u00c1lvarez-Castro C, Franco-Benito M, et al. Adalimumab for treatment of noninfectious uveitis: immunogenicity and clinical relevance of measuring serum drug levels and antidrug antibodies. Ophthalmology. 2016;123(12):2618\u201325.","journal-title":"Ophthalmology"},{"issue":"4","key":"7352_CR25","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/S0002-9394(00)00659-0","volume":"130","author":"DA Jabs","year":"2000","unstructured":"Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, Whitcup SM, Yocum D. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130(4):492\u2013513.","journal-title":"Am J Ophthalmol"},{"key":"7352_CR26","doi-asserted-by":"crossref","unstructured":"Neri P, Perez Y, Pichi F. Precision medicine in uveitis: redefining treatment optimization through biomarkers and tailored therapies. Int Ophthalmol, 2025;45(1):41.","DOI":"10.1007\/s10792-025-03413-9"},{"issue":"2","key":"7352_CR27","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1001\/jamaophthalmol.2022.5584","volume":"141","author":"S Bellur","year":"2023","unstructured":"Bellur S, McHarg M, Kongwattananon W, Vitale S, Sen HN, Kodati S. Antidrug antibodies to tumor necrosis factor \u03b1 inhibitors in patients with noninfectious uveitis. JAMA Ophthalmol. 2023;141(2):150\u20136.","journal-title":"JAMA Ophthalmol"},{"key":"7352_CR28","doi-asserted-by":"crossref","unstructured":"Mortele A, Mortele M, Potvin A, De Schryver I. Clinical impact of drug monitoring in non-infectious uveitis treated with adalimumab. Acta Ophthalmol 2019;97.","DOI":"10.1111\/j.1755-3768.2019.5387"},{"key":"7352_CR29","doi-asserted-by":"publisher","first-page":"100247","DOI":"10.1016\/j.jtauto.2024.100247","volume":"9","author":"I Maccora","year":"2024","unstructured":"Maccora I, Soldovieri S, Oliverio T, de Masi S, Marrani E, Pagnini I, Simonini G. To switch or to swap? Evidence from a meta-analysis for the best treatment approach in childhood chronic uveitis resistant to the I anti-TNF. J Translational Autoimmun. 2024;9:100247.","journal-title":"J Translational Autoimmun"},{"issue":"6","key":"7352_CR30","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S2468-1253(24)00044-X","volume":"9","author":"N Chanchlani","year":"2024","unstructured":"Chanchlani N, Lin S, Bewshea C, Hamilton B, Thomas A, Smith R, Roberts C, Bishara M, Nice R, Lees CW, Sebastian S, Irving PM, Russell RK, McDonald TJ, Goodhand JR, Ahmad T, Kennedy NA, PANTS Consortium. Mechanisms and management of loss of response to anti-TNF therapy for patients with crohn\u2019s disease: 3-year data from the prospective, multicentre PANTS cohort study. Lancet Gastroenterol Hepatol. 2024;9(6):521\u201338.","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"5","key":"7352_CR31","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1038\/s41433-023-02795-3","volume":"38","author":"EO Kreps","year":"2024","unstructured":"Kreps EO, Epps SJ, Consejo A, Dick AD, Guly CM, Ramanan AV. Infliximab in chronic non-infectious paediatric uveitis refractory to previous biologic therapy. Eye. 2024;38(5):871\u20136.","journal-title":"Eye"},{"key":"7352_CR32","doi-asserted-by":"crossref","unstructured":"Chanchlani N, Lin S, Auth MK, Lee CL, Robbins H, Looi S. IMSAT study investigators. Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the immunogenicity to second anti\u2010TNF therapy (IMSAT) therapeutic drug monitoring study[J]. Volume 56. Aliment. Pharmacol. Ther. 2022;56(8);1250-63.","DOI":"10.1111\/apt.17188"},{"issue":"1","key":"7352_CR33","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1136\/annrheumdis-2022-222155","volume":"82","author":"CL Krieckaert","year":"2023","unstructured":"Krieckaert CL, van Tubergen A, Gehin JE, Hern\u00e1ndez-Breijo B, Le M\u00e9l\u00e9do G, Balsa A, et al. EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2023;82(1):65\u201373.","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"7352_CR34","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1016\/j.jid.2023.01.033","volume":"143","author":"A Raharja","year":"2023","unstructured":"Raharja A, Arkir Z, Rinaldi G, Tsakok T, Dasandi T, Guard S, et al. Real-World implementation and outcomes of adalimumab therapeutic drug monitoring in psoriasis: A National specialized center experience. J Invest Dermatol. 2023;143(9):1708\u2013e17164.","journal-title":"J Invest Dermatol"},{"issue":"4","key":"7352_CR35","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s40259-017-0231-8","volume":"31","author":"V Strand","year":"2017","unstructured":"Strand V, Balsa A, Al-Saleh J, Barile-Fabris L, Horiuchi T, Takeuchi T, Marshall L. Immunogenicity of biologics in chronic inflammatory diseases: a systematic review. BioDrugs. 2017;31(4):299\u2013316.","journal-title":"BioDrugs"},{"issue":"4","key":"7352_CR36","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s40259-015-0134-5","volume":"29","author":"SS Thomas","year":"2015","unstructured":"Thomas SS, Borazan N, Barroso N, Duan L, Taroumian S, Kretzmann B, Bardales R, Elashoff D, Vangala S, Furst DE. Comparative immunogenicity of TNF inhibitors: impact on clinical efficacy and tolerability in the management of autoimmune Diseases. A systematic review and Meta-Analysis. BioDrugs. 2015;29(4):241\u201358.","journal-title":"BioDrugs"},{"issue":"14","key":"7352_CR37","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1001\/jama.2011.406","volume":"305","author":"GM Bartelds","year":"2011","unstructured":"Bartelds GM, Krieckaert CL, Nurmohamed MT, van Schouwenburg PA, Lems WF, Twisk JW, Dijkmans BA, Aarden L, Wolbink GJ. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305(14):1460\u20138.","journal-title":"JAMA"},{"issue":"4","key":"7352_CR38","first-page":"e59019","volume":"16","author":"RA Ghanma","year":"2024","unstructured":"Ghanma RA, Steeples L, Pockar S, Sharma V, Chieng A, Ashworth J. Adalimumab (ADA) in pediatric Non-infectious uveitis: an observational study. Cureus. 2024;16(4):e59019.","journal-title":"Cureus"},{"issue":"1","key":"7352_CR39","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1136\/annrheumdis-2014-206237","volume":"74","author":"KA Van Schie","year":"2015","unstructured":"Van Schie KA, Hart MH, de Groot ER, Kruithof S, Aarden LA, Wolbink GJ, Rispens T. The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region. Ann Rheum Dis. 2015;74(1):311\u20134.","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"7352_CR40","doi-asserted-by":"publisher","first-page":"2229","DOI":"10.1074\/jbc.M605984200","volume":"282","author":"C Maas","year":"2007","unstructured":"Maas C, Hermeling S, Bouma B, Jiskoot W, Gebbink MF. A role for protein misfolding in immunogenicity of biopharmaceuticals. J Biol Chem. 2007;282(4):2229\u201336.","journal-title":"J Biol Chem"},{"issue":"5","key":"7352_CR41","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1007\/s11095-011-0414-9","volume":"28","author":"S Kumar","year":"2011","unstructured":"Kumar S, Singh SK, Wang X, Rup B, Gill D. Coupling of aggregation and immunogenicity in biotherapeutics: T- and B-cell immune epitopes May contain aggregation-prone regions. Pharm Res. 2011;28(5):949\u201361.","journal-title":"Pharm Res"},{"issue":"10","key":"7352_CR42","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1093\/rheumatology\/kez030","volume":"58","author":"MJH Doeleman","year":"2019","unstructured":"Doeleman MJH, Van Maarseveen EM, Swart JF. Immunogenicity of biologic agents in juvenile idiopathic arthritis: a systematic review and meta-analysis[J]. Rheumatology. 2019;58(10):1839\u201349.","journal-title":"Rheumatology"},{"issue":"12","key":"7352_CR43","doi-asserted-by":"publisher","first-page":"2782","DOI":"10.3390\/biomedicines12122782","volume":"12","author":"LS Zur Bonsen","year":"2024","unstructured":"Zur Bonsen LS, Knecht VA, R\u00fcbsam A, Pohlmann D, Pleyer U. Adalimumab autoantibodies in uveitis patients: do we need routine drug monitoring? Biomedicines. 2024;12(12):2782.","journal-title":"Biomedicines"},{"issue":"3","key":"7352_CR44","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/nrrheum.2013.4","volume":"9","author":"PA Van Schouwenburg","year":"2013","unstructured":"Van Schouwenburg PA, Rispens T, Wolbink GJ. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. Nat Rev Rheumatol. 2013;9(3):164\u201372.","journal-title":"Nat Rev Rheumatol"},{"issue":"6","key":"7352_CR45","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1080\/17425255.2018.1482278","volume":"14","author":"P Malik","year":"2018","unstructured":"Malik P, Edginton A. Pediatric physiology in relation to the pharmacokinetics of monoclonal antibodies. Expert Opin Drug Metab Toxicol. 2018;14(6):585\u201399.","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"4","key":"7352_CR46","doi-asserted-by":"publisher","first-page":"389","DOI":"10.3390\/pharmaceutics2040389","volume":"2","author":"R Shi","year":"2010","unstructured":"Shi R, Derendorf H. Pediatric dosing and body size in biotherapeutics. Pharmaceutics. 2010;2(4):389\u2013418.","journal-title":"Pharmaceutics"},{"issue":"2","key":"7352_CR47","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1097\/FTD.0000000000000914","volume":"44","author":"A Nassar-Sheikh Rashid","year":"2022","unstructured":"Nassar-Sheikh Rashid A, Schonenberg-Meinema D, Berends SE, van den Berg JM, Math\u00f4t RAA. Population pharmacokinetics of Infliximab in children with juvenile idiopathic arthritis. Ther Drug Monit. 2022;44(2):301\u20137.","journal-title":"Ther Drug Monit"},{"issue":"3","key":"7352_CR48","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.3390\/ijms26031189","volume":"26","author":"BH Huang","year":"2025","unstructured":"Huang BH, Hsu JL, Huang HY, Huang JL, Yeh KW, Chen LC, Lee WI, Yao TC, Ou LS, Lin SJ, Su KW, Wu CY. Early Anti-Drug antibodies predict adalimumab response in juvenile idiopathic arthritis. Int J Mol Sci. 2025;26(3):1189.","journal-title":"Int J Mol Sci"},{"issue":"3","key":"7352_CR49","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.gtc.2023.05.002","volume":"52","author":"A Nasr","year":"2023","unstructured":"Nasr A, Minar P. The role of therapeutic drug monitoring in children[J]. Gastroenterol Clin N Am. 2023;52(3):549\u201363.","journal-title":"Gastroenterol Clin N Am"},{"issue":"12","key":"7352_CR50","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1007\/s00431-020-03750-0","volume":"179","author":"MME Jongsma","year":"2020","unstructured":"Jongsma MME, Winter DA, Huynh HQ, et al. Infliximab in young paediatric IBD patients: it is all about the dosing[J]. Eur J Pediatrics. 2020;179(12):1935\u201344.","journal-title":"Eur J Pediatrics"},{"key":"7352_CR51","doi-asserted-by":"publisher","first-page":"623689","DOI":"10.3389\/fped.2020.623689","volume":"8","author":"KL Kolho","year":"2021","unstructured":"Kolho KL. Therapeutic drug monitoring and outcome of Infliximab therapy in pediatric onset inflammatory bowel disease. Front Pediatr. 2021;8:623689.","journal-title":"Front Pediatr"},{"key":"7352_CR52","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.ajo.2022.03.017","volume":"240","author":"LE Eurelings","year":"2022","unstructured":"Eurelings LE, Missotten TO, van Velthoven ME, Van Daele PL, Van Laar JA, van Hagen PM, et al. Long-term follow-up of patients with uveitis treated with adalimumab: response rates and reasons for discontinuation of therapy. Am J Ophthalmol. 2022;240:194\u2013204.","journal-title":"Am J Ophthalmol"},{"key":"7352_CR53","doi-asserted-by":"crossref","unstructured":"Bromeo AJ, Karaca I, Ghoraba HH, Lyu X, Than NT, Ongpalakorn P et al. Risk factors for development of anti-adalimumab antibodies in non-infectious uveitis. Heliyon. 2024;10(9).","DOI":"10.1016\/j.heliyon.2024.e29313"},{"issue":"7\u20138","key":"7352_CR54","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1080\/09273948.2020.1749857","volume":"29","author":"P Liberman","year":"2021","unstructured":"Liberman P, Berkenstock MK, Burkholder BM, Chaon BC, Thorne JE. Escalation to weekly adalimumab for the treatment of ocular inflammation. Ocul Immunol Inflamm. 2021;29(7\u20138):1564\u20138.","journal-title":"Ocul Immunol Inflamm"},{"issue":"7","key":"7352_CR55","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1136\/ard.2006.065615","volume":"66","author":"GM Bartelds","year":"2007","unstructured":"Bartelds GM, Wijbrandts CA, Nurmohamed MT, Stapel S, Lems WF, Aarden L, et al. Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis. 2007;66(7):921\u20136.","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"7352_CR56","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1111\/apt.12863","volume":"40","author":"D Wolf","year":"2014","unstructured":"Wolf D, D\u2019Haens G, Sandborn WJ, Colombel JF, Van Assche G, Robinson AM, et al. Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severely active ulcerative colitis. Aliment Pharmacol Ther. 2014;40(5):486\u201397.","journal-title":"Aliment Pharmacol Ther"},{"issue":"14","key":"7352_CR57","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1001\/jama.2011.406","volume":"305","author":"GM Bartelds","year":"2011","unstructured":"Bartelds GM, Krieckaert CL, Nurmohamed MT, van Schouwenburg PA, Lems WF, Twisk JW, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305(14):1460\u20138.","journal-title":"JAMA"},{"issue":"6","key":"7352_CR58","first-page":"1043","volume":"35","author":"ST Leinonen","year":"2017","unstructured":"Leinonen ST, Aalto K, Kotaniemi KM, Kivel\u00e4 TT. Anti-adalimumab antibodies in juvenile idiopathic arthritis-related uveitis. Clin Exp Rheumatol. 2017;35(6):1043\u20136.","journal-title":"Clin Exp Rheumatol"},{"issue":"12","key":"7352_CR59","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1136\/annrheumdis-2012-202220","volume":"72","author":"S Garc\u00eas","year":"2013","unstructured":"Garc\u00eas S, Demengeot J, Benito-Garcia E. The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis. Ann Rheum Dis. 2013;72(12):1947\u201355.","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"7352_CR60","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1136\/annrheumdis-2019-216655","volume":"79","author":"JS Smolen","year":"2020","unstructured":"Smolen JS, Landew\u00e9 RB, Bijlsma JW, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685\u201399.","journal-title":"Ann Rheum Dis"},{"key":"7352_CR61","doi-asserted-by":"publisher","first-page":"f740","DOI":"10.1136\/bmj.f740","volume":"346","author":"ME Tucker","year":"2013","unstructured":"Tucker ME. Drug companies lobby against generic versions of biologics. BMJ. 2013;346:f740.","journal-title":"BMJ"},{"issue":"6","key":"7352_CR62","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1053\/j.gastro.2022.01.009","volume":"162","author":"EA Spencer","year":"2022","unstructured":"Spencer EA, Stachelski J, Dervieux T, Dubinsky MC, et al. Failure to achieve target drug concentrations during induction and not HLA-DQA1\u2217 05 carriage is associated with antidrug antibody formation in patients with inflammatory bowel disease[J]. Gastroenterology. 2022;162(6):1746\u20138. e3.","journal-title":"Gastroenterology"},{"issue":"4","key":"7352_CR63","doi-asserted-by":"publisher","first-page":"jjae172","DOI":"10.1093\/ecco-jcc\/jjae172","volume":"19","author":"N Ternette","year":"2025","unstructured":"Ternette N, Liao H, Satsangi J. Association of the HLA-DQA1* 05 allelic gene variants with immunogenicity to Anti-TNF therapeutics\u2014Important differences between Infliximab and Adalimumab[J]. J Crohn\u2019s Colitis. 2025;19(4):jjae172.","journal-title":"J Crohn\u2019s Colitis"},{"issue":"Supplement1","key":"7352_CR64","doi-asserted-by":"publisher","first-page":"i2352","DOI":"10.1093\/ecco-jcc\/jjae190.1480","volume":"19","author":"V Moreno Torres","year":"2025","unstructured":"Moreno Torres V, Mira C, Madero-Vel\u00e1zquez L, Mu\u00f1oz R, Bel\u00e9n-Galipienso O, Cameo JI, et al. P1306 impact of HLA-DQA1* 05 genotype in immunogenicity and response to treatment with tumour necrosis Factor-alpha antagonists in inflammatory bowel disease patients. J Crohn\u2019s Colitis. 2025;19(Supplement1):i2352\u20133.","journal-title":"J Crohn\u2019s Colitis"},{"issue":"3","key":"7352_CR65","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1053\/j.gastro.2017.07.032","volume":"153","author":"JD Feuerstein","year":"2017","unstructured":"Feuerstein JD, Nguyen GC, Kupfer SS, Falck-Ytter Y, Singh S, Gerson L, et al. American gastroenterological association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology. 2017;153(3):827\u201334.","journal-title":"Gastroenterology"},{"issue":"1491","key":"7352_CR66","first-page":"46","volume":"132","author":"A Khan","year":"2019","unstructured":"Khan A, Berahmana AB, Day AS, Barclay ML, Schultz M. New Zealand society of gastroenterology guidelines on therapeutic drug monitoring in inflammatory bowel disease. NZ Med J. 2019;132(1491):46\u201362.","journal-title":"NZ Med J"},{"issue":"10","key":"7352_CR67","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.14309\/ajg.0000000000001396","volume":"116","author":"AS Cheifetz","year":"2021","unstructured":"Cheifetz AS, Abreu MT, Afif W, Cross RK, Dubinsky MC, Loftus EV Jr, et al. A comprehensive literature review and expert consensus statement on therapeutic drug monitoring of biologics in inflammatory bowel disease. Official J Am Coll Gastroenterology| ACG. 2021;116(10):2014\u201325.","journal-title":"Official J Am Coll Gastroenterology| ACG"},{"issue":"8","key":"7352_CR68","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1038\/ajg.2014.146","volume":"109","author":"X Roblin","year":"2014","unstructured":"Roblin X, Rinaudo M, Del Tedesco E, Phelip JM, Genin C, Peyrin-Biroulet L, et al. Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases. Official J Am Coll Gastroenterology| ACG. 2014;109(8):1250\u20136.","journal-title":"Official J Am Coll Gastroenterology| ACG"},{"issue":"9","key":"7352_CR69","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1016\/j.cgh.2016.05.010","volume":"14","author":"GY Melmed","year":"2016","unstructured":"Melmed GY, Irving PM, Jones J, Kaplan GG, Kozuch PL, Velayos FS, et al. Appropriateness of testing for anti\u2013tumor necrosis factor agent and antibody concentrations, and interpretation of results. Clin Gastroenterol Hepatol. 2016;14(9):1302\u20139.","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"9","key":"7352_CR70","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1016\/j.cgh.2019.03.037","volume":"17","author":"K Papamichael","year":"2019","unstructured":"Papamichael K, Cheifetz AS, Melmed GY, Irving PM, Vande Casteele N, Kozuch PL, et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2019;17(9):1655\u201368.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"7352_CR71","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.1007\/s10067-016-3349-z","volume":"35","author":"F Iannone","year":"2016","unstructured":"Iannone F, Sinigaglia L, Favalli EG, Sarzi-Puttini P, Atzeni F, Caporali R, et al. Drug survival of adalimumab in patients with rheumatoid arthritis over 10 years in the real-world settings: high rate remission together with normal function ability. Clin Rheumatol. 2016;35:2649\u201356.","journal-title":"Clin Rheumatol"},{"issue":"3","key":"7352_CR72","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1136\/annrheumdis-2013-203893","volume":"74","author":"DY Chen","year":"2015","unstructured":"Chen DY, Chen YM, Tsai WC, Tseng JC, Chen YH, Hsieh CW, et al. Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis. Ann Rheum Dis. 2015;74(3):e16.","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"7352_CR73","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1093\/ibd\/izaa102","volume":"27","author":"JL Lyles","year":"2021","unstructured":"Lyles JL, Mulgund AA, Bauman LE, Su W, Fei L, Chona DL, et al. Effect of a practice-wide anti-TNF proactive therapeutic drug monitoring program on outcomes in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2021;27(4):482\u201392.","journal-title":"Inflamm Bowel Dis"},{"key":"7352_CR74","doi-asserted-by":"crossref","unstructured":"Pedersen L, Szecsi PB, Johansen PB, Bjerrum PJ. Evaluation of therapeutic drug monitoring in the clinical management of patients with rheumatic diseases: data from a retrospective single-center cohort study. Biol.: Targets Ther. 2020:115\u2009\u2013\u200925.","DOI":"10.2147\/BTT.S262511"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-025-07352-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-025-07352-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-025-07352-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:21:28Z","timestamp":1781612488000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-025-07352-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["7352"],"URL":"https:\/\/doi.org\/10.1186\/s12967-025-07352-y","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]},"assertion":[{"value":"6 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All human serum samples were analysed in strict accordance with a protocol approved by the ethics committee of the First Affiliated Hospital of Fujian Medical University, China (project MRCTA, ECFAH of FMU [2024]525).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"This study adhered to the principles of the Helsinki Declaration. All participants were informed about the nature, purpose, and potential risks of the study, and their consent was documented in writing. For participants who were minors or lacked the capacity to provide consent, written informed consent was obtained from their legal guardians.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1232"}}