{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:00:27Z","timestamp":1790834427654,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to clarify the association between longitudinal adalimumab concentrations, anti-adalimumab antibodies (AAA) levels, and clinical response in Chinese patients with ankylosing spondylitis (AS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A prospective multi-center, observational cohort study of AS patients receiving adalimumab therapy was conducted. Disease activity was assessed with the AS Disease Activity Score (ASDAS), and clinical responders were defined based on ASDAS improvement together with C-reactive protein normalization. Adalimumab concentrations were measured using a validated sandwich immunoassay. Measurement of AAA levels was performed with a laboratory-developed immunoassay system integrating electrochemiluminescence technology with specific immunomagnetic separation, with result reported as signal-to-noise ratio (S\/N).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 140 patients receiving adalimumab monotherapy were included. The median follow-up period was 169 days, and 711 plasma samples were available for adalimumab concentrations and AAA levels measurements. Seven patients had pre-existing AAA, and 120 (90.2%) of the remaining 133 patients tested positive for AAA during follow-up. A total of 48 patients were excluded from the exposure\u2013response relationship dataset owing to pre-existing AAA (n=7), lack of active disease (n=26), incomplete follow-up (n=8), and prolonged dosing intervals (n=7). Among the remaining 92 patients, a total of 58 (63%) achieved clinical response. Adalimumab concentrations were higher, and AAA levels were significantly lower, in responders compared with non-responders at multiple time points. Exposure\u2013response relationship models also revealed a steady-state adalimumab concentration target of 5.1 \u03bcg\/mL and a week-4 concentration target of 3.3 \u03bcg\/mL, corresponding to an 80% probability of clinical response. Thirty-six of 92 patients (39.1%) exhibited AAA-S\/N values exceeding the putative clinically meaningful threshold (AAA-S\/N=10). Patients in the high-AAA group (AAA-S\/N\u226510) had lower drug levels (median: 1.5 \u03bcg\/mL vs. 6.9 \u03bcg\/mL,\n                      <jats:italic>P&amp;lt;<\/jats:italic>\n                      0.0001) and poorer response rates (38.8% vs. 78.6%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0002), relative to those in the low-AAA group (AAA-S\/N&amp;lt;10). Furthermore, patients who were week-4 AAA-positive exhibited a 1.8-fold increased risk of non-response (relative risk, 95% confidence interval, 1.1\u20132.8).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results demonstrate that longitudinal profiles of adalimumab concentrations and AAA levels show a strong association with clinical responses in this Chinese AS cohort, which may inform therapeutic drug monitoring\u2013guided adalimumab treatment strategies that remain to be further validated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov (NCT04875299).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1893483","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:41:11Z","timestamp":1790833271000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal monitoring of adalimumab levels and anti-adalimumab antibodies in Chinese patients with ankylosing spondylitis: a prospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoliang","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizheng","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bikui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Third Affiliated Hospital of Soochow University","place":["Changzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Third Affiliated Hospital of Soochow University","place":["Changzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengxiong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201244","article-title":"Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease","volume":"72","author":"Burmester","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmed.2021.08.003","article-title":"Secondary failure: immune responses to approved protein therapeutics","volume":"27","author":"Lagasse","year":"2021","journal-title":"Trends Mol Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1208\/s12248-025-01050-9","article-title":"Therapeutic drug monitoring of biologics: current practice, challenges and opportunities - a workshop report","volume":"27","author":"Shubow","year":"2025","journal-title":"AAPS J"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.07.032","article-title":"American gastroenterological association institute guideline on therapeutic drug monitoring in inflammatory bowel disease","volume":"153","author":"Feuerstein","year":"2017","journal-title":"Gastroenterology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2024-079830","article-title":"Proactive therapeutic drug monitoring of biologic drugs in adult patients with inflammatory bowel disease, inflammatory arthritis, or psoriasis: a clinical practice guideline","volume":"387","author":"Kawano-Dourado","year":"2024","journal-title":"BMJ"},{"key":"B6","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1136\/annrheumdis-2022-222155","article-title":"EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases","volume":"82","author":"Krieckaert","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/bmjmed-2024-000998","article-title":"Proactive therapeutic drug monitoring of biologic drugs in patients with inflammatory bowel disease, inflammatory arthritis, and psoriasis: systematic review and meta-analysis","volume":"3","author":"Zeraatkar","year":"2024","journal-title":"BMJ Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/s41573-024-01051-x","article-title":"Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics","volume":"23","author":"Carter","year":"2024","journal-title":"Nat Rev Drug Discov"},{"key":"B9","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/s41584-020-00540-8","article-title":"Immunogenicity of biologic agents in rheumatology","volume":"17","author":"Strand","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s2468-1253(21)00223-5","article-title":"Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives","volume":"7","author":"Papamichael","year":"2022","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13112","article-title":"Immunoassay methods used in clinical studies for the detection of anti-drug antibodies to adalimumab and infliximab","volume":"192","author":"Gorovits","year":"2018","journal-title":"Clin Exp Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1401178","article-title":"What are clinically significant anti-drug antibodies and why is it important to identify them","volume":"15","author":"Swanson","year":"2024","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1429544","article-title":"Dynamics and implications of anti-drug antibodies against adalimumab using ultra-sensitive and highly drug-tolerant assays","volume":"15","author":"Ding","year":"2024","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1136\/ard.2010.138594","article-title":"Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores","volume":"70","author":"Machado","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/art.39169","article-title":"Clinical utility of random anti-tumor necrosis factor drug-level testing and measurement of antidrug antibodies on the long-term treatment response in rheumatoid arthritis","volume":"67","author":"Jani","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204172","article-title":"Key findings towards optimising adalimumab treatment: the concentration-effect curve","volume":"74","author":"Pouw","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205554","article-title":"Anti-adalimumab antibodies and adalimumab concentrations in psoriatic arthritis; an association with disease activity at 28 and 52 weeks of follow-up","volume":"73","author":"Vogelzang","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2014.5479","article-title":"Developing a therapeutic range of adalimumab serum concentrations in management of psoriasis: A step toward personalized treatment","volume":"151","author":"Menting","year":"2015","journal-title":"JAMA Dermatol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14318","article-title":"Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial","volume":"46","author":"Nakase","year":"2017","journal-title":"Aliment Pharmacol Ther"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12738","article-title":"Early adalimumab and anti-adalimumab antibody levels for prediction of primary nonresponse in ankylosing spondylitis patients","volume":"13","author":"Ding","year":"2020","journal-title":"Clin Transl Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/s2468-1253(19)30012-3","article-title":"Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study","volume":"4","author":"Kennedy","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.07.028","article-title":"Defining the therapeutic range for adalimumab and predicting response in psoriasis: A multicenter prospective observational cohort study","volume":"139","author":"Wilkinson","year":"2019","journal-title":"J Invest Dermatol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1097\/ftd.0000000000001204","article-title":"Best practice for therapeutic drug monitoring of infliximab: position statement from the international association of therapeutic drug monitoring and clinical toxicology","volume":"46","author":"Alsoud","year":"2024","journal-title":"Ther Drug Monit"},{"key":"B24","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1093\/ecco-jcc\/jjad009","article-title":"A model-based tool for guiding infliximab induction dosing to maximize long-term deep remission in children with inflammatory bowel diseases","volume":"17","author":"Kantasiripitak","year":"2023","journal-title":"J Crohns Colitis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-020-00408-z","article-title":"Comparison of the efficacy and safety of adalimumab (Humira) and the adalimumab biosimilar candidate (HS016) in chinese patients with active ankylosing spondylitis: A multicenter, randomized, double-blind, parallel, phase III clinical trial","volume":"34","author":"Su","year":"2020","journal-title":"BioDrugs"},{"key":"B26","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s40744-025-00808-z","article-title":"Real-world analysis of initial clinical response and future outcomes among patients with rheumatoid arthritis initiating and remaining on a first-line tumor necrosis factor inhibitor in the united states","volume":"13","author":"Charles-Schoeman","year":"2026","journal-title":"Rheumatol Ther"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010211","article-title":"Longitudinal dynamics of SARS-CoV-2-specific cellular and humoral immunity after natural infection or BNT162b2 vaccination","volume":"17","author":"Almendro-Vazquez","year":"2021","journal-title":"PloS Pathog"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03738-2","article-title":"SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses","volume":"596","author":"Turner","year":"2021","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1814","article-title":"Multiple layers of B cell memory with different effector functions","volume":"10","author":"Dogan","year":"2009","journal-title":"Nat Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjac164","article-title":"A systematic review on the interest of drug-tolerant assay in the monitoring of inflammatory bowel disease","volume":"17","author":"Barrau","year":"2023","journal-title":"J Crohns Colitis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1550655","article-title":"The first WHO reference panel for Infliximab anti-drug antibodies: a step towards harmonizing therapeutic drug monitoring","volume":"16","author":"Wadhwa","year":"2025","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1177\/17562848211037849","article-title":"Dynamics of serum concentrations of antibodies to infliximab: a new approach for predicting secondary loss of response in inflammatory bowel diseases","volume":"14","author":"Grasmeier","year":"2021","journal-title":"Therap Adv Gastroenterol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s40259-020-00458-3","article-title":"Systematic review and principal components analysis of the immunogenicity of adalimumab","volume":"35","author":"Borrega","year":"2021","journal-title":"BioDrugs"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2023.113436","article-title":"Drug-tolerant detection of anti-drug antibodies in an antigen-binding assay using europium chelate fluorescence","volume":"514","author":"van Strien","year":"2023","journal-title":"J Immunol Methods"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2019-001047","article-title":"Methotrexate effect on immunogenicity and long-term maintenance of adalimumab in axial spondyloarthritis: a multicentric randomised trial","volume":"6","author":"Ducourau","year":"2020","journal-title":"RMD Open"},{"key":"B36","doi-asserted-by":"publisher","first-page":"109248","DOI":"10.2139\/ssrn.4125006","article-title":"A randomized, double-blind phase III study to demonstrate the clinical similarity of biosimilar SCT630 to reference adalimumab in Chinese patients with moderate to severe plaque psoriasis","volume":"112","author":"Yu","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-021-00502-w","article-title":"Efficacy, safety and immunogenicity of AVT02 versus originator adalimumab in subjects with moderate to severe chronic plaque psoriasis: A multicentre, double-blind, randomised, parallel group, active control, phase III study","volume":"35","author":"Feldman","year":"2021","journal-title":"BioDrugs"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1097\/mcg.0000000000001636","article-title":"Week 2 adalimumab levels predict short-term clinical remission in patients with inflammatory bowel disease","volume":"56","author":"Buffone","year":"2022","journal-title":"J Clin Gastroenterol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0073-0","article-title":"Prospective observational evaluation of time-dependency of adalimumab immunogenicity and drug concentrations: the POETIC study","volume":"113","author":"Ungar","year":"2018","journal-title":"Am J Gastroenterol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12341","article-title":"Predicting treatment response in psoriasis using serum levels of adalimumab and etanercept: a single-centre, cohort study","volume":"169","author":"Mahil","year":"2013","journal-title":"Br J Dermatol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14943","article-title":"Influence of early adalimumab serum levels on immunogenicity and long-term outcome of anti-TNF naive Crohn's disease patients: the usefulness of rapid testing","volume":"48","author":"Verstockt","year":"2018","journal-title":"Aliment Pharmacol Ther"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000401","article-title":"Post-induction high adalimumab drug levels predict biological remission at week 24 in patients with crohn's disease","volume":"12","author":"Zittan","year":"2021","journal-title":"Clin Transl Gastroenterol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.06.003","article-title":"Proactive monitoring of adalimumab trough concentration associated with increased clinical remission in children with crohn's disease compared with reactive monitoring","volume":"157","author":"Assa","year":"2019","journal-title":"Gastroenterology"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.01.044","article-title":"Higher vs standard adalimumab induction dosing regimens and two maintenance strategies: randomized SERENE CD trial results","volume":"162","author":"D'Haens","year":"2022","journal-title":"Gastroenterology"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1893483\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:41:12Z","timestamp":1790833272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1893483\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":44,"alternative-id":["10.3389\/fimmu.2026.1893483"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1893483","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"1893483"}}