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The most frequently reported SOCs included General Disorders and Administration Site Conditions (12,940 cases), Injury, Poisoning, and Procedural Complications (5,503 cases), and Gastrointestinal Disorders (4,346 cases).Key findings revealed that infection-related AEs and injection-site reactions were the predominant safety concerns. The median onset time of AEs was 235 days (IQR: 46\u2013832 days), with 19.8% of cases occurring within the first month of treatment. Notably, 25.5% of reported AEs required hospitalization, while fatal and life-threatening outcomes accounted for 0.9% and 1.4% of cases, respectively. This comprehensive analysis confirms the multisystemic involvement and prolonged latency of TNF-\u03b1 inhibitors-associated AEs in pediatric populations. While these agents remain vital for managing chronic inflammatory diseases, the findings advocate for enhanced clinical vigilance. We propose a tiered monitoring protocol prioritizing infection surveillance (e.g., serial inflammatory markers), systematic injection-site evaluations, and longitudinal organ function assessments, particularly during the initial treatment phase, to optimize therapeutic risk-benefit ratios.<\/jats:p>","DOI":"10.1371\/journal.pone.0328465","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:48:02Z","timestamp":1764701282000},"page":"e0328465","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety profile of TNF- alpha Inhibitors in pediatric patients: A post-marketing surveillance study based on the FAERS database"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9124-936X","authenticated-orcid":true,"given":"Yanmo","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5868-2487","authenticated-orcid":true,"given":"Qin-xuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"issue":"5","key":"pone.0328465.ref001","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.3390\/ijms22052719","article-title":"The Role of Tumor Necrosis Factor Alpha (TNF-\u03b1) in Autoimmune Disease and Current TNF-\u03b1 Inhibitors in Therapeutics","volume":"22","author":"D-I Jang","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"4","key":"pone.0328465.ref002","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1002\/art.43041","article-title":"Trends in New Use of Disease-Modifying Antirheumatic Drugs for Juvenile Idiopathic Arthritis Among Commercially Insured Children in the United States from 2001 to 2022","volume":"77","author":"P Yalamanchili","year":"2025","journal-title":"Arthritis Rheumatol"},{"issue":"10","key":"pone.0328465.ref003","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1111\/apt.17217","article-title":"The inexorable increase of biologic exposure in paediatric inflammatory bowel disease: a Scottish, population-based, longitudinal study","volume":"56","author":"CJ Burgess","year":"2022","journal-title":"Aliment Pharmacol Ther"},{"issue":"4","key":"pone.0328465.ref004","first-page":"222","article-title":"Invasive infections related to anti-TNF-\u03b1 therapy in pediatric inflammatory bowel disease","volume":"48","author":"L Zheng","year":"2021","journal-title":"Int J Pediatrics"},{"key":"pone.0328465.ref005","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.curtheres.2018.12.001","article-title":"Pediatric drug development: challenges and opportunities","volume":"90","author":"C Spadoni","year":"2018","journal-title":"Curr Ther Res Clin Exp"},{"issue":"1","key":"pone.0328465.ref006","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13690-024-01295-4","article-title":"The epidemiology of drug-related hospital admissions in paediatrics - 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