{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T19:49:18Z","timestamp":1768420158954,"version":"3.49.0"},"reference-count":24,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Tumor necrosis factor-\u03b1 (TNF\u03b1) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-\u03b1 inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or interval extension. Objective: We aim to identify patient-, disease-, and treatment-related predictors of successful TNF-\u03b1 inhibitor withdrawal in children with non-systemic JIA. Methods: In this prospective, randomized, open-label, single-center study, 76 children with non-systemic JIA in stable remission for \u226524 months on etanercept or adalimumab were enrolled. At the time of TNF-\u03b1 inhibitor discontinuation, all patients underwent a comprehensive evaluation, including a clinical examination, laboratory tests (serum calprotectin [S100 proteins] and high-sensitivity C-reactive protein [hsCRP]), and advanced joint imaging (musculoskeletal ultrasound and magnetic resonance imaging [MRI]) to assess subclinical disease activity. Patients were randomized (1:1:1, sealed-envelope allocation) to one of three predefined tapering strategies: (I) abrupt discontinuation; (II) extension of dosing intervals (etanercept 0.8 mg\/kg every 2 weeks; adalimumab 24 mg\/m2 every 4 weeks); or (III) gradual dose reduction (etanercept 0.4 mg\/kg weekly; adalimumab 12 mg\/m2 every 2 weeks). Follow-up visits were scheduled at 3, 6, 9, 12, and 18 months to monitor for disease relapse. Results: Higher baseline Childhood Health Assessment Questionnaire (CHAQ) scores (\u22652), elevated serum calprotectin [S100 proteins] and hsCRP levels at withdrawal, imaging evidence of subclinical synovitis, and a history of uveitis were all significantly associated with increased risk of flare. No significant associations were found for other clinical or demographic characteristics. Conclusions: Early significant clinical response, absence of subclinical disease activity, and concomitant low-dose methotrexate therapy were key predictors of sustained drug-free remission. These findings may inform personalized strategies for biologic tapering in pediatric JIA.<\/jats:p>","DOI":"10.3390\/ph19010125","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T07:30:34Z","timestamp":1768203034000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toward Personalized Withdrawal of TNF-\u03b1 Inhibitors in Non-Systemic Juvenile Idiopathic Arthritis: Predictors of Biologic-Free Remission and Flare"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3874-4721","authenticated-orcid":false,"given":"Ekaterina I.","family":"Alexeeva","sequence":"first","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"},{"name":"Clinical Institute of Children\u2019s Health Named After N.F. Filatov, Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia"},{"name":"Association of Pediatric Rheumatologists, 107078 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3720-9452","authenticated-orcid":false,"given":"Irina T.","family":"Tsulukiya","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana M.","family":"Dvoryakovskaya","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"},{"name":"Clinical Institute of Children\u2019s Health Named After N.F. Filatov, Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia"},{"name":"Association of Pediatric Rheumatologists, 107078 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2370-3182","authenticated-orcid":false,"given":"Ivan A.","family":"Kriulin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"},{"name":"Association of Pediatric Rheumatologists, 107078 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1878-4467","authenticated-orcid":false,"given":"Dmitry A.","family":"Kudlay","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia"},{"name":"Laboratory of Personalized Medicine and Molecular Immunology, National Research Center\u2014Institute of Immunology of Federal Medical-Biological Agency of Russia, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8959-1606","authenticated-orcid":false,"given":"Anna N.","family":"Fetisova","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria S.","family":"Botova","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana Y.","family":"Kriulina","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"},{"name":"Association of Pediatric Rheumatologists, 107078 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5732-8873","authenticated-orcid":false,"given":"Elizaveta A.","family":"Krekhova","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya M.","family":"Kondratyeva","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiri Sh.","family":"Shingarova","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"},{"name":"Clinical Institute of Children\u2019s Health Named After N.F. Filatov, Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Y.","family":"Kokina","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyona N.","family":"Shilova","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, National Medical Research Center of Children\u2019s Health, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1180-8086","authenticated-orcid":false,"given":"Mikhail M.","family":"Kostik","sequence":"additional","affiliation":[{"name":"Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, 194100 Saint-Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1542\/pir.2022-005623","article-title":"Juvenile Idiopathic Arthritis","volume":"44","author":"Long","year":"2023","journal-title":"Pediatr. 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