{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:37:03Z","timestamp":1790498223119,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,5,25]],"date-time":"2019-05-25T00:00:00Z","timestamp":1558742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"Objective<\/jats:title>To assess the frequency of cardiovascular and venous thromboembolic events in clinical studies of baricitinib, an oral, selective JAK1 and JAK2 inhibitor approved in more than 50 countries for the treatment of moderately\u2010to\u2010severely active rheumatoid arthritis (RA<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>Data were pooled from 9 RA<\/jats:styled-content> studies. Placebo comparison up to 24 weeks included data from 6 studies. Randomized dose comparison between baricitinib doses of 2 mg and 4 mg used data from 4 studies and from the associated long\u2010term extension study. The data analysis set designated \u201cAll\u2010bari\u2010RA<\/jats:styled-content>\u201d included all baricitinib exposures at any dose.<\/jats:p><\/jats:sec>Results<\/jats:title>Overall, 3,492 RA<\/jats:styled-content> patients received baricitinib (7,860 patient\u2010years of exposure). No imbalance compared to the placebo group was seen in the incidence of major adverse cardiovascular events (MACE) (incidence rates [IRs] of 0.5 per 100 patient\u2010years for placebo and 0.8 per 100 patient\u2010years for 4 mg baricitinib), arterial thrombotic events (ATE) (IRs of 0.5 per 100 patient\u2010years for placebo and 0.5 per 100 patient\u2010years for 4 mg baricitinib), or congestive heart failure (CHF) broad term (IRs of 4.3 per 100 patient\u2010years for placebo and 2.4 per 100 patient\u2010years for 4 mg baricitinib). Deep vein thrombosis (DVT<\/jats:styled-content>)\/pulmonary embolism (PE<\/jats:styled-content>) were reported in 0 of 1,070 patients treated with placebo and 6 of 997 patients treated with 4 mg baricitinib during the placebo\u2010controlled period; these events were serious in 2 of 6 patients, while all 6 had risk factors and 1 patient developed DVT<\/jats:styled-content>\/PE<\/jats:styled-content> after discontinuation of the study drug. In the 2 mg\u20134 mg\u2010extended data analysis set, IR<\/jats:styled-content>s of DVT<\/jats:styled-content>\/PE<\/jats:styled-content> were comparable between the doses across event types (IR<\/jats:styled-content>s of 0.5 per 100 patient\u2010years in those receiving 2 mg baricitinib and 0.6 per 100 patient\u2010years in those receiving 4 mg baricitinib). In the All\u2010bari\u2010RA<\/jats:styled-content> data analysis set, the rates were stable over time, with an IR<\/jats:styled-content> of DVT<\/jats:styled-content>\/PE<\/jats:styled-content> of 0.5 per 100 patient\u2010years.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>In RA<\/jats:styled-content> clinical trials, no association was found between baricitinib treatment and the incidence of MACE<\/jats:styled-content>, ATE<\/jats:styled-content>, or CHF<\/jats:styled-content>. With regard to incidence of DVT<\/jats:styled-content>\/PE<\/jats:styled-content>, 6 events occurred in patients treated with 4 mg baricitinib, but no cases of DVT<\/jats:styled-content>\/PE<\/jats:styled-content> were reported in the placebo group. During longer\u2010term evaluation, the incidence of DVT<\/jats:styled-content>\/PE<\/jats:styled-content> was similar between the baricitinib dose groups, with consistent IR<\/jats:styled-content> values over time, and this was similar to the rates previously reported in patients with RA<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40841","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T06:04:28Z","timestamp":1548050668000},"page":"1042-1055","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":164,"title":["Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"71","author":[{"given":"Peter C.","family":"Taylor","sequence":"first","affiliation":[{"name":"University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Weinblatt","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd R.","family":"Burmester","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence P.","family":"Rooney","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Witt","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad D.","family":"Walls","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maher","family":"Issa","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A.","family":"Salinas","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chadi","family":"Saifan","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabela","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Gonz\u00e1lez\u2010Gay","sequence":"additional","affiliation":[{"name":"Hospital Universitario Marqu\u00e9s de Valdecilla IDIVAL and University of Cantabria, Santander, Spain and University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39953"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1608345"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210094"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507247"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902819"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210275"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/2012.jama.11741"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22039"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-014-0435-y"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-203101"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2016.10.006"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep252"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200112)44:12<2737::AID-ART460>3.0.CO;2-#"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2016.07.026"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH08-08-0551"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203380"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-014-2492-7"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-eular.1627"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206478"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.150613"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213271"},{"issue":"39","key":"e_1_2_8_23_1","first-page":"S100","article-title":"The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis","volume":"23","author":"Aletaha D","year":"2005","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1994.tb05705.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12251"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380107"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212461"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1136\/annrheumdis-2017-eular.1325","article-title":"Analysis of neutrophils, lymphocytes, and platelets in pooled phase 2 and phase 3 studies of baricitinib for rheumatoid arthritis [abstract]","volume":"76","author":"Kremer JM","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx145"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201669"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33322"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2011.153536"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209315"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2014.10.012"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.071244"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2016.05.014"},{"issue":"10","key":"e_1_2_8_37_1","article-title":"Comparative cardiovascular safety of tocilizumab vs etanercept in rheumatoid arthritis: results of a randomized, parallel\u2010group, multicenter, noninferiority, phase 4 clinical trial [abstract]","volume":"68","author":"Giles JT","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2018.03.012"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40084"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-015-1311-6"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu408"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.92"},{"issue":"10","key":"e_1_2_8_43_1","article-title":"Incidence of thromboembolic events in the tofacitinib rheumatoid arthritis, psoriasis, psoriatic arthritis and ulcerative colitis development programs [abstract]","volume":"69","author":"Mease PJ","year":"2017","journal-title":"Arthritis Rhuematol"},{"issue":"10","key":"e_1_2_8_44_1","article-title":"Comparative risk of venous thromboembolism with tofacitinib versus tumor necrosis factor inhibitors: a cohort study of rheumatoid arthritis patients [abstract]","volume":"70","author":"Desai RJ","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31115-2"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31116-4"},{"issue":"10","key":"e_1_2_8_47_1","article-title":"A phase 3, randomized, double\u2010blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate [abstract]","volume":"70","author":"Fleischmann R","year":"2018","journal-title":"Arthritis Rheumatol"},{"issue":"10","key":"e_1_2_8_48_1","article-title":"Upadacitinib as monotherapy: a phase 3 randomized controlled double\u2010blind study in patients with active rheumatoid arthritis and inadequate response to methotrexate [abstract]","volume":"70","author":"Smolen JS","year":"2018","journal-title":"Arthritis Rheumatol"},{"issue":"10","key":"e_1_2_8_49_1","doi-asserted-by":"crossref","DOI":"10.1002\/art.41384","article-title":"A phase 3, randomized, controlled trial comparing upadacitinib monotherapy to MTX monotherapy in MTX\u2010na\u00efve patients with active rheumatoid arthritis [abstract]","volume":"70","author":"Van Vollenhoven R","year":"2018","journal-title":"Arthritis Rheumatol"},{"issue":"10","key":"e_1_2_8_50_1","article-title":"Long\u2010term safety and efficacy of upadacitinib (ABT\u2010494), an oral JAK\u20101 inhibitor in patients with rheumatoid arthritis in an open label extension study [abstract]","volume":"69","author":"Genovese MC","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"e_1_2_8_51_1","unstructured":"US Food and Drug Administration.Advisory committee meeting: baricitinib for treatment of moderate to severe rheumatoid arthritis. May 2018. URL:https:\/\/www.fda.gov\/downloads\/AdvisoryCommittees\/CommitteesMeetingMaterials\/Drugs\/ArthritisAdvisoryCommittee\/UCM606024.pdf."},{"issue":"10","key":"e_1_2_8_52_1","article-title":"Cardiovascular safety during treatment with baricitinib in rheumatoid arthritis [abstract]","volume":"69","author":"Weinblatt M","year":"2017","journal-title":"Arthritis Rheumatol"},{"issue":"10","key":"e_1_2_8_53_1","article-title":"Cardiovascular safety\u2013update from up to 6 years of treatment with baricitinib in rheumatoid arthritis clinical trials [abstract]","volume":"70","author":"Weinblatt M","year":"2018","journal-title":"Arthritis Rheumatol"}],"container-title":["Arthritis & Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.40841","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40841","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.40841","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40841","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:50:47Z","timestamp":1759945847000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.40841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,25]]},"references-count":52,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1002\/art.40841"],"URL":"https:\/\/doi.org\/10.1002\/art.40841","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,25]]},"assertion":[{"value":"2018-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}