{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:30:15Z","timestamp":1791307815007,"version":"4.3.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"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>Background<\/jats:title>\n                    <jats:p>Although several medications have been linked to inflammatory bowel disease (IBD), the association between most drugs and IBD remains unclear. This study aimed to identify medications most frequently reported in connection with IBD by analyzing large-scale data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japan Adverse Drug Event Report (JADER) database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We extracted reports of drug-associated IBD adverse events from FAERS and performed external validation using JADER. Disproportionality analyses of suspected drugs were conducted using four methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Additional analyses included time-to-onset (TTO) assessment, Weibull distribution modeling, and subgroup analyses by age, sex, and IBD subtype to evaluate signal stability and clinical characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The FAERS database yielded 52,395 reports of drug-associated IBD, corresponding to 50,426 patients.Females accounted for a higher proportion of reports than males, with the majority of cases occurring in individuals aged 18\u201364 years. The annual number of reports showed an overall upward trend. Among drugs reported at least 50 times, 17 met all four algorithmic threshold criteria and were classified as positive signals. Anti\u2013tumor necrosis factor-alpha (anti-TNF-\u03b1) inhibitors ranked highest by reporting frequency, whereas isotretinoin demonstrated the strongest signal intensity. External validation using JADER confirmed consistent signals for certain anti-TNF-\u03b1 inhibitors, anti\u2013interleukin biologic agents, conventional immunosuppressants, and antibiotics. Time-to-onset analysis revealed that the median onset of IBD occurred within one year for most drug-associated cases. The Weibull model indicated an \u201cearly failure\u2013type\u201d onset pattern for the majority of positive signals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>From a pharmacovigilance perspective, this study provides a comprehensive overview of medications associated with IBD, offering clinically relevant insights. Our findings deliver real-world evidence to support the identification and monitoring of drug-associated IBD; however, confirmation in large prospective cohort studies remains necessary.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1873829","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:46:20Z","timestamp":1783403180000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Drug-associated inflammatory bowel disease: a real-world pharmacovigilance study using the FAERS and JADER databases"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuou","family":"Ying","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Shen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhan","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongfei","family":"Feng","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zejiong","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhekai","family":"Ying","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyi","family":"Ju","sequence":"additional","affiliation":[{"name":"Hangzhou Third People\u2019s Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiannong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.m2023.0142","article-title":"Treatment strategies in inflammatory bowel diseases","volume":"120","author":"Stallmach","year":"2023","journal-title":"Dtsch Arztebl Int"},{"key":"B2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41591-019-0744-4","article-title":"Common IBD pathogenic mechanisms","volume":"26","author":"Stower","year":"2020","journal-title":"Nat Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/goaf082","article-title":"Global, regional, and national burden of inflammatory bowel disease from 1990 to 2021: findings from the Global Burden of Disease 2021","volume":"13","author":"Ruan","year":"2025","journal-title":"Gastroenterol Rep (Oxf)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08940-0","article-title":"Global evolution of inflammatory bowel disease across epidemiologic stages","volume":"642","author":"Hracs","year":"2025","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fgstr.2024.1452430","article-title":"Innate immune cells in the pathogenesis of inflammatory bowel disease - 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