{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:03:59Z","timestamp":1784610239327,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is a widely recognized chronic inflammatory disease. Leflunomide, upadacitinib, and baricitinib are frequently used to treat inflammatory diseases, including RA, although understanding of their associated adverse drug events (ADEs) remains limited. This study analyzed ADEs reported for these drugs based on the United States FAERS database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data were extracted from the FAERS database, including ADE reports from January 2004 to December 2024. ADE reports related to leflunomide, upadacitinib, and baricitinib were described and categorized using the preferred term (PT) and system organ class (SOC) based on the International Dictionary of Medical Terms (MedDRA). The baseline characteristics of leflunomide, upadacitinib, and baricitinib were analyzed; the readxl R package was used for variable analysis. The ggplot2 R package was used to plot temporal trend line charts of ADE reports for each drug used for RA treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The baseline analysis showed that the number of ADE reports was 10,445 for leflunomide, 27,433 for upadacitinib, and 2,638 for baricitinib. The number of ADE reports for baricitinib following RA treatment was highest in 2019, whereas the number of reports for leflunomide peaked in 2020, whereas those relative to upadacitinib reached their peak in 2022. Baricitinib-related ADE reports in RA treatment included infections and infestations and blood and lymphatic system disorders. Leflunomide-related ADE reports involved hepatic disorders and congenital, familial, and hereditary diseases. Upadacitinib-related ADE reports included surgical and medical procedures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study, based on the FAERS database, identified ADEs in leflunomide, upadacitinib, and baricitinib, to provide a reference for improving drug safety and therapeutic efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1753446","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:19:55Z","timestamp":1784607595000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic analysis of adverse reaction signals induced by leflunomide, upadacitinib, and baricitinib in the treatment of rheumatoid arthritis: a FAERS database analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Jizheng","family":"Dang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University-Town Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University-Town Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.3390\/cells10112857","article-title":"Management of rheumatoid arthritis: an overview","volume":"10","author":"Radu","year":"2021","journal-title":"Cells"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.rdc.2022.02.010","article-title":"Rheumatoid arthritis: early diagnosis and treatment","volume":"48","author":"Cush","year":"2022","journal-title":"Rheum Dis Clin N Am"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e070856","DOI":"10.1136\/bmj-2022-070856","article-title":"Therapeutic advances in rheumatoid arthritis","volume":"384","author":"Brown","year":"2024","journal-title":"BMJ"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"686155","DOI":"10.3389\/fimmu.2021.686155","article-title":"Promising therapeutic targets for treatment of rheumatoid arthritis","volume":"12","author":"Huang","year":"2021","journal-title":"Front Immunol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.1007\/s10067-023-06654-0","article-title":"What are the core recommendations for rheumatoid arthritis care? 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