{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:24:49Z","timestamp":1793651089631,"version":"4.5.1"},"reference-count":48,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Editage"},{"name":"Ministry of Health, Labour, and Welfare","award":["22FE1002"],"award-info":[{"award-number":["22FE1002"]}]},{"name":"JSPS","award":["20K10480"],"award-info":[{"award-number":["20K10480"]}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["60447919"],"award-info":[{"award-number":["60447919"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,5,31]]},"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To compare the risk of cardiovascular events among Janus kinase inhibitors (JAKIs), biological disease-modifying antirheumatic drugs (bDMARDs) (tumour necrosis factor inhibitors (TNFIs) and non-TNFIs) and methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using Japanese claims data, patients with RA were enrolled in this study if they had at least one ICD-10 code (M05 or M06), were new users of JAKIs, bDMARDs or MTX between July 2013 and July 2020 and being 18 years old or older. The incidence rate (IR), IR ratio and adjusted hazard ratio (aHR (95% CI)) of cardiovascular events including venous thromboembolism, arterial thrombosis, acute myocardial infarction and stroke were calculated. A time-dependent Cox regression model adjusted for patient characteristics at baseline was used to calculate aHR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In 53\u2009448 cases, IRs\/1000 patient-years of the overall cardiovascular events were 10.1, 6.8, 5.4, 9.1 and 11.3 under the treatments with JAKIs, bDMARDs, TNFIs, non-TNFIs and MTX, respectively. The adjusted HRs of JAKIs for overall cardiovascular events were 1.7 (1.1 to 2.5) versus TNFIs without MTX and 1.7 (1.1 to 2.7) versus TNFIs with MTX.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Among patients with RA, individuals using JAKIs had a significantly higher risk of overall cardiovascular events than TNFIs users, which was attributed to the difference in the risk between JAKIs and TNFIs versus MTX. These data should be interpreted with caution because of the limitations associated with the claims database.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-003885","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T20:46:38Z","timestamp":1718657198000},"page":"e003885","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Increased risk of cardiovascular events under the treatments with Janus kinase inhibitors versus biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a retrospective longitudinal population-based study using the Japanese health insurance database"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1640-1373","authenticated-orcid":false,"given":"Ryoko","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Publich Health and Epidemiology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan"},{"name":"Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan"},{"name":"Institute of Rheumatology, Tokyo Women\u2019s Medical University Hospital, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisuke","family":"Inoue","sequence":"additional","affiliation":[{"name":"Showa University Research Administration Center, Showa University, Shinagawa-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6418-2603","authenticated-orcid":false,"given":"Masayoshi","family":"Harigai","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan"},{"name":"Institute of Rheumatology, Tokyo Women\u2019s Medical University Hospital, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"2025090312542557000_10.2.e003885.1","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2019.1660028"},{"key":"2025090312542557000_10.2.e003885.2","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s40265-020-01349-1","article-title":"Selectivity of Janus kinase inhibitors in rheumatoid arthritis and other immune-mediated inflammatory diseases: is expectation the root of all headache","volume":"80","author":"Harigai","year":"2020","journal-title":"Drugs"},{"key":"2025090312542557000_10.2.e003885.3","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0140-6736(21)00438-4","article-title":"Current and future status of JAK inhibitors","volume":"398","author":"McLornan","year":"2021","journal-title":"Lancet"},{"key":"2025090312542557000_10.2.e003885.4","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218398"},{"key":"2025090312542557000_10.2.e003885.5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/mr\/roac017","article-title":"Drug treatment algorithm and recommendations from the 2020 update of the Japan college of rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication","volume":"33","author":"Kawahito","year":"2023","journal-title":"Mod Rheumatol"},{"key":"2025090312542557000_10.2.e003885.6","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223356"},{"key":"2025090312542557000_10.2.e003885.7","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210275"},{"key":"2025090312542557000_10.2.e003885.8","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/acr.22039","article-title":"Risk of venous thromboembolism in patients with rheumatoid arthritis","volume":"65","author":"Kim","year":"2013","journal-title":"Arthritis Care & Research"},{"key":"2025090312542557000_10.2.e003885.9","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201669"},{"key":"2025090312542557000_10.2.e003885.10","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.amjmed.2014.11.025","article-title":"Risk of venous thromboembolism in patients with rheumatoid arthritis: initiating disease-modifying Antirheumatic drugs","volume":"128","author":"Kim","year":"2015","journal-title":"Am J Med"},{"key":"2025090312542557000_10.2.e003885.11","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2019-001013","article-title":"Incidence of inpatient venous thromboembolism in treated patients with rheumatoid arthritis and the association with switching biologic or targeted synthetic disease-modifying Antirheumatic drugs (Dmards) in the real-world setting","volume":"5","author":"Liang","year":"2019","journal-title":"RMD Open"},{"key":"2025090312542557000_10.2.e003885.12","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1080\/14397595.2018.1519889","article-title":"Higher risk of hospitalized infection, cardiovascular disease, and fracture in patients with rheumatoid arthritis determined using the Japanese health insurance database","volume":"29","author":"Kasai","year":"2019","journal-title":"Mod Rheumatol"},{"key":"2025090312542557000_10.2.e003885.13","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.autrev.2019.05.005","article-title":"Rheumatoid arthritis (RA) and cardiovascular disease","volume":"18","author":"Blum","year":"2019","journal-title":"Autoimmun Rev"},{"key":"2025090312542557000_10.2.e003885.14","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/acr.20371","article-title":"Systematic review and meta-analysis: anti-tumor necrosis factor \u0391 therapy and cardiovascular events in rheumatoid arthritis","volume":"63","author":"Barnabe","year":"2011","journal-title":"Arthritis Care & Research"},{"key":"2025090312542557000_10.2.e003885.15","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211209"},{"key":"2025090312542557000_10.2.e003885.16","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1007\/s10067-021-05911-4","article-title":"Risk of venous thromboembolism associated with Janus kinase inhibitors for rheumatoid arthritis: case presentation and literature review","volume":"40","author":"Mori","year":"2021","journal-title":"Clin Rheumatol"},{"key":"2025090312542557000_10.2.e003885.17","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1002\/art.41580","article-title":"Venous thromboembolism risk with JAK inhibitors: a meta-analysis","volume":"73","author":"Yates","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"2025090312542557000_10.2.e003885.18","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223357"},{"key":"2025090312542557000_10.2.e003885.19","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223050"},{"key":"2025090312542557000_10.2.e003885.20","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109927"},{"key":"2025090312542557000_10.2.e003885.21","unstructured":"FDA Drug Safety Communication, Available: https:\/\/www.fda.gov\/media\/151936\/download"},{"key":"2025090312542557000_10.2.e003885.22","unstructured":"Direct healthcare profesional communication:Xeljanz (tofacitinib): increased risk of major adverse cardiovascular events and malignancies with use of tofacitinib relative to TNF-alpha inhibitors, Available: https:\/\/www.ema.europa.eu\/en\/medicines\/dhpc\/xeljanz-tofacitinib-increased-risk-major-adverse-cardiovascular-events-malignancies-use-tofacitinib"},{"key":"2025090312542557000_10.2.e003885.23","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208698"},{"key":"2025090312542557000_10.2.e003885.24","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1177\/0961203320952853","article-title":"The risk of hospitalized infection in patients with systemic lupus erythematosus treated with hydroxychloroquine","volume":"29","author":"Sakai","year":"2020","journal-title":"Lupus"},{"key":"2025090312542557000_10.2.e003885.25","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/art.39399","article-title":"Comparative risk of hospitalized infection associated with biologic agents in rheumatoid arthritis patients enrolled in Medicare","volume":"68","author":"Yun","year":"2016","journal-title":"Arthritis & Rheumatology"},{"key":"2025090312542557000_10.2.e003885.26","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlr.0000182534.19832.83"},{"key":"2025090312542557000_10.2.e003885.27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1080\/14397595.2019.1583711","article-title":"Safety profile of Baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment: an integrated analysis of phases 2 and 3 trials","volume":"30","author":"Harigai","year":"2020","journal-title":"Mod Rheumatol"},{"key":"2025090312542557000_10.2.e003885.28","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216761"},{"key":"2025090312542557000_10.2.e003885.29","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2023-003489","article-title":"Risk of major adverse cardiovascular events in patients with rheumatoid arthritis treated with conventional synthetic, biologic and targeted synthetic disease-modifying Antirheumatic drugs: observational data from the German RABBIT register","volume":"9","author":"Meissner","year":"2023","journal-title":"RMD Open"},{"key":"2025090312542557000_10.2.e003885.30","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1002\/art.40841","article-title":"Cardiovascular safety during treatment with baricitinib in rheumatoid arthritis","volume":"71","author":"Taylor","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"2025090312542557000_10.2.e003885.31","doi-asserted-by":"crossref","first-page":"i34","DOI":"10.1093\/rheumatology\/key287","article-title":"Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis","volume":"58","author":"Harigai","year":"2019","journal-title":"Rheumatology (Oxford)"},{"key":"2025090312542557000_10.2.e003885.32","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/acr.24966","article-title":"Effectiveness and safety of tofacitinib in Canadian patients with rheumatoid arthritis: primary results from a prospective observational study","volume":"75","author":"Haraoui","year":"2023","journal-title":"Arthritis Care & Research"},{"key":"2025090312542557000_10.2.e003885.33","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.83"},{"key":"2025090312542557000_10.2.e003885.34","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1253\/circj.CJ-17-1128","article-title":"Anticoagulation therapy for venous thromboembolism in the real world - from the COMMAND VTE registry","volume":"82","author":"Yamashita","year":"2018","journal-title":"Circ J"},{"key":"2025090312542557000_10.2.e003885.35","first-page":"201","article-title":"Evaluation of VTE, MACE, and serious infections among patients with RA treated with Baricitinib compared to Tnfi: a multi-database study of patients in routine care using disease registries and claims databases","volume":"10","author":"Salinas","year":"2023","journal-title":"Rheumatol Ther"},{"key":"2025090312542557000_10.2.e003885.36","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-222824"},{"key":"2025090312542557000_10.2.e003885.37","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221915"},{"key":"2025090312542557000_10.2.e003885.38","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223762"},{"key":"2025090312542557000_10.2.e003885.39","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/acr.23875","article-title":"Comparative risk of cardiovascular events with biologic and synthetic disease-modifying Antirheumatic drugs in patients with rheumatoid arthritis: A systematic review and meta-analysis","volume":"72","author":"Singh","year":"2020","journal-title":"Arthritis Care & Research"},{"key":"2025090312542557000_10.2.e003885.40","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.200265"},{"key":"2025090312542557000_10.2.e003885.41","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1002\/art.41293","article-title":"Biologics may prevent cardiovascular events in rheumatoid arthritis by inhibiting coronary plaque formation and stabilizing high-risk lesions","volume":"72","author":"Karpouzas","year":"2020","journal-title":"Arthritis & Rheumatology"},{"key":"2025090312542557000_10.2.e003885.42","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-017-1439-1","article-title":"Methotrexate and anti-tumor necrosis factor treatment improves endothelial function in patients with inflammatory arthritis","volume":"19","author":"Deyab","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"2025090312542557000_10.2.e003885.43","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJMe2117663","article-title":"Risks and benefits of janus kinase inhibitors in rheumatoid arthritis - past, present, and future","volume":"386","author":"Singh","year":"2022","journal-title":"N Engl J Med"},{"key":"2025090312542557000_10.2.e003885.44","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218510"},{"key":"2025090312542557000_10.2.e003885.45","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221051"},{"key":"2025090312542557000_10.2.e003885.46","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1080\/14397595.2020.1836789","article-title":"A pooled safety analysis of Peficitinib (Asp015K) in Asian patients with rheumatoid arthritis treated over a median of 2 years","volume":"31","author":"Takeuchi","year":"2021","journal-title":"Mod Rheumatol"},{"key":"2025090312542557000_10.2.e003885.47","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.k1036","article-title":"Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications","volume":"361","author":"England","year":"2018","journal-title":"BMJ"},{"key":"2025090312542557000_10.2.e003885.48","doi-asserted-by":"crossref","DOI":"10.1186\/s12891-021-04259-9","article-title":"The validity of the claims-based definition of rheumatoid arthritis evaluated in 64 hospitals in Japan","volume":"22","author":"Kubota","year":"2021","journal-title":"BMC Musculoskelet Disord"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2023-003885","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T19:54:37Z","timestamp":1756929277000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2023-003885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":48,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,6,17]]},"published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1136\/rmdopen-2023-003885"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2023-003885","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6]]}}}