{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:37:29Z","timestamp":1787510249664,"version":"build-2736575974"},"reference-count":39,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T00:00:00Z","timestamp":1609286400000},"content-version":"unspecified","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,11,9]]},"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Janus kinases (JAK) inhibitors demonstrated to be effective in the treatment of adult patients with moderate-to-severe active rheumatoid arthritis (RA) but have been associated with serious cardiovascular and serious events. Two systematic reviews and network meta-analyses will be carried aiming to compare the relative safety of the different JAK inhibitors with regard to the risk of (1) cardiovascular and thromboembolic events and (2) serious infections in patients with RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>PUBMED, Embase, Cochrane Controlled Register of Trials and ClinicalTrials.gov will be searched in order to identify randomised controlled trials evaluating the efficacy and safety of JAK inhibitors in patients with RA. The following events will be assessed: (1) any cardiovascular event; major adverse cardiovascular events and venous thromboembolism and (2) any infection; serious infections; herpes zoster infection and tuberculosis. Search terms will comprise RA and drugs names, including the thesaurus terms and the International Nonproprietary Names. The assessment of the methodological quality of the included studies will be performed through the RoB 2 tool: a revised Cochrane risk of bias tool for randomised trials. Network meta-analyses will be performed using STATA V.13.0. For each outcome, treatments will be ranked according to the probability of being the safest (best) alternative using the surface under the cumulative ranking curve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval is not required as no primary data are collected. This systematic review will be disseminated through peer-reviewed publications and at conference meetings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-041420","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T02:21:25Z","timestamp":1678846885000},"page":"e041420","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Risk of infections and cardiovascular and venous thromboembolic events associated with JAK inhibitors in rheumatoid arthritis: protocols of two systematic reviews and network meta-analyses"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-4718","authenticated-orcid":false,"given":"Carlos","family":"Alves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-4718","authenticated-orcid":false,"given":"Ana","family":"Penedones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo","family":"Mendes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Batel-Marques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"2024101904053094000_10.12.e041420.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2007.04.005"},{"key":"2024101904053094000_10.12.e041420.2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216655"},{"key":"2024101904053094000_10.12.e041420.3","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key276"},{"key":"2024101904053094000_10.12.e041420.4","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1177\/1060028019839650","article-title":"Baricitinib: the second FDA-approved JAK inhibitor for the treatment of rheumatoid arthritis","volume":"53","author":"Mogul","year":"2019","journal-title":"Ann Pharmacother"},{"key":"2024101904053094000_10.12.e041420.5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/1744666X.2019.1544892","article-title":"Upadacitinib for the treatment of rheumatoid arthritis","volume":"15","author":"Serhal","year":"2019","journal-title":"Expert Rev Clin Immunol"},{"key":"2024101904053094000_10.12.e041420.6","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214846"},{"key":"2024101904053094000_10.12.e041420.7","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1093\/rheumatology\/kez087","article-title":"A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis","volume":"58","author":"Bechman","year":"2019","journal-title":"Rheumatology"},{"key":"2024101904053094000_10.12.e041420.8","unstructured":"Food and Drug Administration . FDA approves Boxed warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR)."},{"key":"2024101904053094000_10.12.e041420.9","unstructured":"European Medicines Agency . Increased risk of blood clots in lungs and death with higher dose of Xeljanz (tofacitinib) for rheumatoid arthritis."},{"key":"2024101904053094000_10.12.e041420.10","unstructured":"European Medicines Agency . Rinvoq."},{"key":"2024101904053094000_10.12.e041420.11","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"},{"key":"2024101904053094000_10.12.e041420.12","unstructured":"European Medicines Agency . 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EMA confirms Xeljanz to be used with caution in patients at high risk of blood clots."},{"key":"2024101904053094000_10.12.e041420.38","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key432"},{"key":"2024101904053094000_10.12.e041420.39","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s40259-019-00333-w","article-title":"Selective JAKinibs: prospects in inflammatory and autoimmune diseases","volume":"33","author":"T Virtanen","year":"2019","journal-title":"BioDrugs"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2020-041420","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T07:07:29Z","timestamp":1729321649000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2020-041420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,31]]},"published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1136\/bmjopen-2020-041420"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2020-041420","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]}}}