{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:29:37Z","timestamp":1793449777048,"version":"4.5.0"},"reference-count":27,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2022,2,4]]},"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p>The US Food and Drug Administration (FDA) has recently added a new \u2018black box warning\u2019 on all currently approved Janus kinase (JAK) inhibitors indicated for the treatment of arthritis and other inflammatory conditions based on results from the ORAL Surveillance study of tofacitinib versus tumour necrosis factor alpha inhibitors in rheumatoid arthritis. This is a warning difficult to ignore because the data, being from a randomised controlled trial, are of high fidelity and hard to reproach. It is especially problematic because safety data for all the other JAK inhibitors will be pending for several years. So how might we proceed, without being bound by our stasis? The lack of absolute certainty seems to require a pragmatic approach to the routine care use of JAK inhibitors. The patients who were at greatest risk were older and had other risk factors for the corresponding adverse events, in keeping with effect modification. This highlights the need to focus on risk stratification when tailoring therapy. In this viewpoint, we propose a simple illustration to guide clinical decision-making. First, identify general risk factors for venous thromboembolic event (VTE), major adverse cardiac event (MACE) and cancer (age&gt;65 years and smoking) and whether there is a previous history of VTE, MACE or cancer. Then, evaluate risk based on the number of other risk factors for VTE and the number of other risk factors for MACE. Ultimately, \u2018treat-to-target\u2019 will in the end always be \u2018treat-to-agreement\u2019. As we have done in the past, and will do in the future, the optimal treatment strategy will have to be tailored based on individual patient risk factors and preferences in a shared-decision process.<\/jats:p>","DOI":"10.1136\/rmdopen-2022-002236","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T11:30:31Z","timestamp":1645615831000},"page":"e002236","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":84,"title":["Waiting for JAK inhibitor safety data"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct02092467","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03915964","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02629159","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6439-397X","authenticated-orcid":false,"given":"Tue Wenzel","family":"Kragstrup","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"},{"name":"Diagnostic Center, Silkeborg Regional Hospital, Silkeborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8931-8482","authenticated-orcid":false,"given":"Bente","family":"Glintborg","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Copenhagen, Kobenhavn, Denmark"},{"name":"DANBIO and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, University Hospital of Copenhagen Rigshospitalet, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie L","family":"Svensson","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, University Hospital of Copenhagen Rigshospitalet, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"McMaster","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Austin Health, Heidelberg, Victoria, Australia"},{"name":"Department of Clinical Pharmacology and Therapeutics, Austin Health, Heidelberg, Victoria, Australia"},{"name":"The Centre for Digital Transformation of Health, University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3156-3418","authenticated-orcid":false,"given":"Philip C","family":"Robinson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Queensland School of Clinical Medicine, Brisbane, Queensland, Australia"},{"name":"Department of Rheumatology, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7079-1587","authenticated-orcid":false,"given":"Bent","family":"Deleuran","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"},{"name":"Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-8883","authenticated-orcid":false,"given":"David FL","family":"Liew","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Austin Health, Heidelberg, Victoria, Australia"},{"name":"Department of Clinical Pharmacology and Therapeutics, Austin Health, Heidelberg, Victoria, Australia"},{"name":"Department of Medicine, University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"2025090313371616000_8.1.e002236.1","unstructured":"Administration UFaD . 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Available: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/203214s028,208246s013,213082s003lbl.pdf [Accessed 2 Feb 2022]."},{"key":"2025090313371616000_8.1.e002236.4","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":"2025090313371616000_8.1.e002236.5","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218398"},{"key":"2025090313371616000_8.1.e002236.6","unstructured":"Administration UFaD . 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Arthritis Rheumatol 2021;73."},{"key":"2025090313371616000_8.1.e002236.10","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1056\/NEJMoa2109927","article-title":"Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis","volume":"386","author":"Ytterberg","year":"2022","journal-title":"N Engl J Med"},{"key":"2025090313371616000_8.1.e002236.11","unstructured":"Pfizer . Pfizer announces modification to ongoing tofacitinib FDA post-marketing requirement study in patients with rheumatoid arthritis, 2019."},{"key":"2025090313371616000_8.1.e002236.12","unstructured":"Charles-Schoeman CHC , Guan S , Parikh N . Relationship Between Paraoxonase-1 Genotype, Activity, and Malignancies in Patients with RA Receiving Tofacitinib [abstract]. 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