{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:55:35Z","timestamp":1781654135379,"version":"3.54.5"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":53,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Secondary drug failure to adalimumab remains a significant challenge in managing Juvenile Idiopathic Arthritis (JIA), with anti-adalimumab antibodies (ADA_ab) implicated as a potential mechanism. This study examines the relationship between ADA_ab formation and loss of response (LOR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      In this retrospective, longitudinal study, a combination of conventional statistical methods and machine-learning algorithms were employed to investigate the association of adalimumab drug levels (ADA_drug) and ADA_ab, alongside clinical variables, on LOR among JIA patients treated between December 2016 and May 2024. LOR was defined as active disease. Among 184 patients, ADA_ab and ADA_drug emerged as the strongest predictors of LOR in random-forest analysis. In multiple logistic regression, higher ADA_ab levels were independently associated with increased risk of LOR (OR 1.18, 95% CI 1.08\u20131.29,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003), while higher ADA_drug levels were associated with reduced risk (OR 0.81, 95% CI 0.68\u20130.95,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0103). An ADA_ab threshold of 69 AU\/mL was associated with an eightfold increase in LOR (OR 8.04, 95% CI 2.8\u201326.1,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002). Patients with high ADA_ab and undetectable ADA_drug had the highest risk of LOR (OR 28.24, 95% CI 7.11\u2013111.63,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001). Kaplan\u2013Meier analysis demonstrated that 71% of patients with elevated ADA_ab experienced LOR within 12\u2009months\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>High ADA_ab levels are a significant predictor of LOR in JIA patients treated with adalimumab, particularly when coupled with low drug levels. We also report clinically meaningful one-year LOR rates. These findings support the use of therapeutic drug monitoring, which may help optimise treatment and improve long-term disease control.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12969-026-01213-8","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T09:36:07Z","timestamp":1777109767000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-adalimumab antibodies are associated with loss of response in juvenile idiopathic arthritis"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2290-6988","authenticated-orcid":false,"given":"Mikhail","family":"Carrim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2087-9437","authenticated-orcid":false,"given":"Muhammad R. A.","family":"Shipa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aicha","family":"Bouraoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5774-6821","authenticated-orcid":false,"given":"Toka","family":"AlSulaim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4188-9427","authenticated-orcid":false,"given":"Corinne","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R. W.","family":"Glanville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Leandro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4760-1674","authenticated-orcid":false,"given":"Debajit","family":"Sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,25]]},"reference":[{"issue":"10","key":"1213_CR1","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1093\/rheumatology\/ket248","volume":"52","author":"F McErlane","year":"2013","unstructured":"McErlane F, Foster HE, Davies R, Lunt M, Watson KD, et al. Biologic treatment response among adults with juvenile idiopathic arthritis: results from the British society for rheumatology biologics Register. Rheumatol (Oxford). 2013, Oct;52(10):1905\u201313. https:\/\/doi.org\/10.1093\/rheumatology\/ket248.","journal-title":"Rheumatol (Oxford)"},{"key":"1213_CR2","doi-asserted-by":"publisher","unstructured":"Skrabl-BaumgartnerA, Erwa W, Muntean W, Jahnel J. Anti-adalimumab antibodies in juvenile idiopathic arthritis: frequent association with loss of response. Scand J Rheumatol. 2015;44(5). https:\/\/doi.org\/10.3109\/03009742.2015.1022213.","DOI":"10.3109\/03009742.2015.1022213"},{"key":"1213_CR3","doi-asserted-by":"publisher","unstructured":"Marino A, Real-Fern\u00e1ndez F, Rovero P, Giani T, Pagnini I, Cimaz R, et al. Anti-adalimumab antibodies in a cohort of patients with juvenile idiopathic arthritis: incidence and clinical correlations. Clin Rheumatol. 2018;37(5). https:\/\/doi.org\/10.1007\/s10067-018-4057-7","DOI":"10.1007\/s10067-018-4057-7"},{"key":"1213_CR4","doi-asserted-by":"publisher","unstructured":"Doeleman MJH, De Roock S, El Amrani M, Van Maarseveen EM, Wulffraat NM, Swart JF. Association of adalimumab trough concentrations and treatment response in patients with juvenile idiopathic arthritis. Rheumatol (United Kingdom). 2022;61(1). https:\/\/doi.org\/10.1093\/rheumatology\/keab35","DOI":"10.1093\/rheumatology\/keab35"},{"key":"1213_CR5","doi-asserted-by":"publisher","unstructured":"Doeleman MJH, Van Maarseveen EM, Swart JF. Immunogenicity of biologic agents in juvenile idiopathic arthritis: a systematic review and meta-analysis. Rheumatol (United Kingdom). 2019;58(10). https:\/\/doi.org\/10.1093\/rheumatology\/kez030","DOI":"10.1093\/rheumatology\/kez030"},{"key":"1213_CR6","doi-asserted-by":"publisher","unstructured":"Brunelli JB, Silva CA, Pasoto SG, Saa CGS, Kozu KT, Goldenstein-Schainberg C, et al. Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switching. Clin Rheumatol. 2020;39(2). https:\/\/doi.org\/10.1007\/s10067-019-04798-6","DOI":"10.1007\/s10067-019-04798-6"},{"issue":"3","key":"1213_CR7","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, et al. Early Anti-drug antibodies predict adalimumab response in juvenile idiopathic arthritis. Int J Mol Sci. 2025, Jan, 30;26(3):1189. 10.3390\/ijms26031189","journal-title":"Int J Mol Sci"},{"key":"1213_CR8","doi-asserted-by":"crossref","unstructured":"White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med. 2011;30(4).","DOI":"10.1002\/sim.4067"},{"key":"1213_CR9","doi-asserted-by":"crossref","unstructured":"Resche-Rigon M, White IR. Multiple imputation by chained equations for systematically and sporadically missing multilevel data. Stat Methods Med Res. 2018;27(6).","DOI":"10.1177\/0962280216666564"}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-026-01213-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-026-01213-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-026-01213-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:29:00Z","timestamp":1781652540000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12969-026-01213-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,25]]},"references-count":9,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1213"],"URL":"https:\/\/doi.org\/10.1186\/s12969-026-01213-8","relation":{},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,25]]},"assertion":[{"value":"20 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No ethical approval is required for retrospective clinical database analysis under National Health Service Research Ethics Committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37"}}