{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T05:13:31Z","timestamp":1794287611797,"version":"4.9.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the risk of major adverse cardiovascular events (<jats:styled-content style=\"fixed-case\">MACE<\/jats:styled-content>) in patients with rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>) treated with tocilizumab compared to those treated with the tumor necrosis factor inhibitor etanercept.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This randomized, open\u2010label, parallel\u2010group trial enrolled patients with active seropositive <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> (n =\u00a03,080) who had an inadequate response to conventional synthetic disease\u2010modifying antirheumatic drugs and who had at least 1 cardiovascular (<jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content>) risk factor. Patients were randomly assigned 1:1 to receive open\u2010label tocilizumab at 8\u00a0mg\/kg\/month or etanercept at 50 mg\/week. All patients were followed up for a mean of 3.2 years. The primary end point was comparison of time to first occurrence of <jats:styled-content style=\"fixed-case\">MACE<\/jats:styled-content>. The trial was powered to exclude a relative hazard ratio for <jats:styled-content style=\"fixed-case\">MACE<\/jats:styled-content> of 1.8 or higher in the tocilizumab group compared to the etanercept group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>By week 4 of treatment, the serum low\u2010density lipoprotein cholesterol, high\u2010density lipoprotein cholesterol, and triglyceride levels were a median 11.1%, 5.7%, and 13.6% higher, respectively, in patients receiving tocilizumab compared to those receiving etanercept (each <jats:italic>P<\/jats:italic> &lt; 0.001). During follow\u2010up, 83 <jats:styled-content style=\"fixed-case\">MACE<\/jats:styled-content> occurred in the tocilizumab group compared to 78 <jats:styled-content style=\"fixed-case\">MACE<\/jats:styled-content> in the etanercept group. The estimated hazard ratio for occurrence of <jats:styled-content style=\"fixed-case\">MACE<\/jats:styled-content> in the tocilizumab group relative to the etanercept group was 1.05 (95% confidence interval 0.77\u20131.43). Results were similar in sensitivity analyses and in the on\u2010treatment population analysis. Adverse events occurred more frequently in the tocilizumab group, including serious infection and gastrointestinal perforation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of this trial, which provide insights into the <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content> safety of tocilizumab as compared to etanercept, ruled out a risk for occurrence of <jats:styled-content style=\"fixed-case\">MACE<\/jats:styled-content> of 1.43 or higher in patients treated with tocilizumab. This result should be interpreted in the context of the clinical efficacy and non\u2010<jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content> safety of tocilizumab.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41095","type":"journal-article","created":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T08:58:50Z","timestamp":1567155530000},"page":"31-40","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":221,"title":["Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8792-0402","authenticated-orcid":false,"given":"Jon T.","family":"Giles","sequence":"first","affiliation":[{"name":"Columbia University College of Physicians &amp; Surgeons  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed","family":"Sattar","sequence":"additional","affiliation":[{"name":"University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherine","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Rutgers Robert Wood Johnson Medical School  New Brunswick New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Ridker","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Gay","sequence":"additional","affiliation":[{"name":"University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Warne","sequence":"additional","affiliation":[{"name":"Roche Products Ltd.  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