{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T14:05:10Z","timestamp":1775570710744,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"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>Introduction<\/jats:title>\n                    <jats:p>Inflammatory bowel disease (IBD) is a chronic immune-mediated gastrointestinal disease, and its global incidence is on the rise, which seriously affects the quality of life of patients. Infliximab is the key therapeutic drug for IBD, and a comprehensive safety assessment is needed. In this pharmacovigilance study, we investigated the adverse events (AE) of infliximab in IBD patients by analyzing the reports submitted to the FDA\u2019s Adverse Event Reporting System (FAERS) database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed the reports of AEs related to infliximab in FAERS database (2004-2024). Disproportionality analysis (ROR, PRR, BCPNN) was used to identify the safety signals in the general population and gender subgroups. Based on the model of ROR, the influence of gender difference and combined medication was evaluated. The onset time (TTO) and Weibull shape parameter (WSP) were used to analyze and evaluate the occurrence time and risk trend of AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 80,138 AE reports, 57 Preferred Term (PT) and 14 System Organ Classification (SOC) signals were detected (ROR025 &amp;gt; 1, PRR &amp;gt; 2, \u03c7\u00b2 &amp;gt; 4, N \u2265 3, IC025 &amp;gt; 0). Some emerging AE signals, such as Horner\u2019s syndrome and Henoch-Schoenlein Henoch-Schonlein purpura nephritis (not mentioned in the drug label), suggest that there are new safety hazards. Females (50.7%) exhibited 67 signals, predominantly immune-related (e.g., lupus-like syndrome, N = 1028, ROR = 7.09), while males (41.8%) showed 42 signals, mainly cardiovascular (e.g., blood pressure fluctuation, ROR = 29.33) and infectious. Combined medication (67.3%) will increase cardiovascular risk, while monotherapy is associated with immune\/tumor-related AEs (such as breast cancer, ROR = 1.2). Kidney and urinary system diseases (ROR = 21.84) are an under-reported problem. Time trade-off analysis (TTO, N = 15,682) showed that the median treatment duration was 620 days, and the early treatment failed (Weibull \u03b2=0.73). In addition, there was a significant gender difference in the incidence of AEs related to infliximab in IBD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study emphasizes that there is a significant burden of AEs in IBD patients treated with infliximab, and finds new safety signals that need further verification. The characteristics of gender-specific AEs suggest that gender-specific monitoring is needed. Women have a higher risk of immune\/tumor events, while men have a higher risk of cardiovascular\/infectious AEs. Combined medication will aggravate cardiovascular risk, while monotherapy will increase immune\/carcinogenic risk. The occurrence of early AEs highlights the necessity of early close monitoring. These findings suggest that pharmacovigilance needs to be improved to optimize the safety of infliximab.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1662405","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:04:06Z","timestamp":1774368246000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacovigilance analysis of infliximab in inflammatory bowel disease: novel safety signals and sex-specific adverse event profiles from the FAERS database (2004\u20132024)"],"prefix":"10.3389","volume":"17","author":[{"given":"Wei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Minimally Invasive Common Surgery, Suzhou Ninth People\u2019s Hospital, Xuzhou Medical University Suzhou Bay Clinical College","place":["Suzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaochen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital","place":["Suzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Common Surgery, Suzhou Ninth People\u2019s Hospital, Xuzhou Medical University Suzhou Bay Clinical College","place":["Suzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenguo","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Suzhou Ninth People\u2019s Hospital, Xuzhou Medical University Suzhou Bay Clinical College","place":["Suzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Renmin Hospital of Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital","place":["Suzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genhai","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Common Surgery, Suzhou Ninth People\u2019s Hospital, Xuzhou Medical University Suzhou Bay Clinical College","place":["Suzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08940-0","article-title":"Global evolution of inflammatory bowel disease across epidemiologic stages","volume":"643","author":"Hracs","year":"2025","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1093\/ecco-jcc\/jjw168","article-title":"3rd European evidence-based consensus on the diagnosis and management of Crohn\u2019s disease 2016: Part 1: diagnosis and medical management","volume":"11","author":"Gomoll\u00f3n","year":"2017","journal-title":"J Crohns Colitis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050516","article-title":"Infliximab for induction and maintenance therapy for ulcerative colitis","volume":"353","author":"Rutgeerts","year":"2005","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08512-4","article-title":"Maintenance infliximab for Crohn\u2019s disease: the ACCENT I randomised trial","volume":"359","author":"Hanauer","year":"2002","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199710093371502","article-title":"A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn\u2019s disease","volume":"337","author":"Targan","year":"1997","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030815","article-title":"Infliximab maintenance therapy for fistulizing Crohn\u2019s disease","volume":"350","author":"Sands","year":"2004","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1053\/j.gastro.2006.11.041","article-title":"Adalimumab for maintenance of clinical response and remission in patients with Crohn\u2019s disease: the CHARM trial","volume":"132","author":"Colombel","year":"2007","journal-title":"Gastroenterology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904492","article-title":"Infliximab, azathioprine, or combination therapy for Crohn\u2019s disease","volume":"362","author":"Colombel","year":"2010","journal-title":"N Engl J Med"},{"key":"B9","unstructured":"Remicade (infliximab) [Prescribing information\n          \n          \n          \n          2025"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17313","article-title":"Meta-analysis: the efficacy of therapeutic drug monitoring of anti-TNF-therapy in inflammatory bowel disease","volume":"57","author":"Sethi","year":"2023","journal-title":"Aliment Pharmacol Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae444","article-title":"Incidence and risk factors for invasive fungal infections in patients initiating tumor necrosis factor-alpha inhibitors for inflammatory bowel disease and rheumatoid arthritis","volume":"80","author":"Hennessee","year":"2025","journal-title":"Clin Infect Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3884-2","article-title":"Diverse patterns of anti-TNF-\u03b1-induced lupus: case series and review of the literature","volume":"37","author":"Shovman","year":"2018","journal-title":"Clin Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1053\/j.gastro.2013.05.048","article-title":"Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis","volume":"146","author":"Sandborn","year":"2014","journal-title":"Gastroenterology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1573353","article-title":"Exploring the complexities of disproportionality analysis in pharmacovigilance: reflections on the READUS-PV guideline and a call to action","volume":"16","author":"Hammad","year":"2025","journal-title":"Front Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s40290-024-00549-4","article-title":"Disproportionality analysis and causal inference in drug safety","volume":"39","author":"Scosyrev","year":"2025","journal-title":"Pharmaceut Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.001","article-title":"Risk factors for idiosyncratic drug-induced liver injury","volume":"138","author":"Chalasani","year":"2010","journal-title":"Gastroenterology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1259908","article-title":"A pharmacovigilance study of etoposide in the FDA adverse event reporting system (FAERS) database, what does the real world say","volume":"14","author":"Cui","year":"2023","journal-title":"Front Pharmacol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199920020-00002","article-title":"The medical dictionary for regulatory activities (MedDRA)","volume":"20","author":"Brown","year":"1999","journal-title":"Drug Saf"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1742","article-title":"Quantitative signal detection using spontaneous ADR reporting","volume":"18","author":"Bate","year":"2009","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/pds.668","article-title":"A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions","volume":"11","author":"van Puijenbroek","year":"2002","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200225060-00001","article-title":"Use of screening algorithms and computer systems to efficiently signal higher-than-expected combinations of drugs and events in the US FDA\u2019s spontaneous reports database","volume":"25","author":"Szarfman","year":"2002","journal-title":"Drug Saf"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1001","article-title":"The reporting odds ratio and its advantages over the proportional reporting ratio","volume":"13","author":"Rothman","year":"2004","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/pds.677","article-title":"Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports","volume":"10","author":"Evans","year":"2001","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-17","article-title":"Estimating time-to-onset of adverse drug reactions from spontaneous reporting databases","volume":"14","author":"Leroy","year":"2014","journal-title":"BMC Med Res Methodol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/jcpt.13024","article-title":"Time-to-onset analysis of amiodarone-associated thyroid dysfunction","volume":"45","author":"Kinoshita","year":"2020","journal-title":"J Clin Pharm Ther"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2021.1948529","article-title":"The impact of anti-TNF\u03b1 agents on weight-related changes: new insights from a real-world pharmacovigilance study using the FDA adverse event reporting system (FAERS) database","volume":"21","author":"Mazhar","year":"2021","journal-title":"Expert Opin Biol Ther"},{"key":"B27","article-title":"The epidemiology and risk factors of inflammatory bowel disease","volume":"8","author":"Ye","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"B28","article-title":"Drug-induced nephrotoxicity","volume":"78","author":"Naughton","year":"2008","journal-title":"Am Fam Physician"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep270","article-title":"Adverse events and efficacy of TNF-alpha blockade with infliximab in patients with systemic lupus erythematosus: long-term follow-up of 13 patients","volume":"48","author":"Aringer","year":"2009","journal-title":"Rheumatol (Oxford)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1080\/14740338.2016.1240783","article-title":"Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis","volume":"15","author":"Minozzi","year":"2016","journal-title":"Expert Opin Drug Saf"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.10.001","article-title":"Tumor necrosis factor antagonist mechanisms of action: a comprehensive review","volume":"117","author":"Tracey","year":"2008","journal-title":"Pharmacol Ther"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nm939","article-title":"Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases","volume":"9","author":"Feldmann","year":"2003","journal-title":"Nat Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-022-01903-6","article-title":"Renal manifestations in inflammatory bowel disease: a systematic review","volume":"57","author":"van Hoeve","year":"2022","journal-title":"J Gastroenterol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.19041","article-title":"Chronic inflammatory demyelinating polyneuropathy in patients with Crohn\u2019s disease on infliximab therapy","volume":"13","author":"Almuntashri","year":"2021","journal-title":"Cureus"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.09.033","article-title":"A meta-analysis of cytokines in major depression","volume":"67","author":"Dowlati","year":"2010","journal-title":"Biol Psychiatry"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/s0399-8320(07)89438-3","article-title":"Maladie de Crohn et syndrome SAPHO, au cours d\u2019un traitement \u00e0 l\u2019infliximab: cas clinique et revue de la litt\u00e9rature","volume":"31","author":"Van Den Eynde","year":"2007","journal-title":"Gastroenterol Clin Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2018.09.001","article-title":"SAPHO syndrome in pediatric patients with inflammatory bowel disease treated with infliximab","volume":"50","author":"Marrani","year":"2018","journal-title":"Dig Liver Dis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.19.2275","article-title":"Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and Malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials","volume":"295","author":"Bongartz","year":"2006","journal-title":"JAMA"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20956","article-title":"Adalimumab safety in global clinical trials of patients with Crohn\u2019s disease","volume":"15","author":"Colombel","year":"2009","journal-title":"Inflamm Bowel Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.049460","article-title":"Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine","volume":"54","author":"Kandiel","year":"2005","journal-title":"Gut"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.01.004","article-title":"Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn\u2019s disease: a meta-analysis","volume":"7","author":"Siegel","year":"2009","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.cgh.2014.05.015","article-title":"Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis","volume":"13","author":"Kotlyar","year":"2015","journal-title":"Clin Gastroenterol Hepatol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1662405\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:04:08Z","timestamp":1774368248000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1662405\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":43,"alternative-id":["10.3389\/fimmu.2026.1662405"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1662405","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"article-number":"1662405"}}