{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:36:44Z","timestamp":1791419804185,"version":"4.3.3"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012068","name":"Health and Care Research Wales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012068","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,1]]},"DOI":"10.1093\/rheumatology\/key339","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T15:19:27Z","timestamp":1539962367000},"page":"953-962","source":"Crossref","is-referenced-by-count":255,"title":["Clinical significance of Janus Kinase inhibitor selectivity"],"prefix":"10.1093","volume":"58","author":[{"given":"Ernest H","family":"Choy","sequence":"first","affiliation":[{"name":"CREATE Centre, Section of Rheumatology, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,12,1]]},"reference":[{"key":"2019052308203693500_key339-B1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1186\/gb-2004-5-12-253","article-title":"The Janus kinases (Jaks)","volume":"5","author":"Yamaoka","year":"2004","journal-title":"Genome Biol"},{"key":"2019052308203693500_key339-B2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/rheumatology\/kep329","article-title":"Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor","volume":"49","author":"Dayer","year":"2010","journal-title":"Rheumatology (Oxford)"},{"key":"2019052308203693500_key339-B3","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1242\/jcs.00963","article-title":"The JAK\/STAT signaling pathway","volume":"117","author":"Rawlings","year":"2004","journal-title":"J Cell Sci"},{"key":"2019052308203693500_key339-B4","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s40265-017-0701-9","article-title":"JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects","volume":"77","author":"Banerjee","year":"2017","journal-title":"Drugs"},{"key":"2019052308203693500_key339-B5","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0092-8674(00)81166-6","article-title":"Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses","volume":"93","author":"Rodig","year":"1998","journal-title":"Cell"},{"key":"2019052308203693500_key339-B6","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0092-8674(00)81167-8","article-title":"Jak2 is essential for signaling through a variety of cytokine receptors","volume":"93","author":"Parganas","year":"1998","journal-title":"Cell"},{"key":"2019052308203693500_key339-B7","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1126\/science.270.5237.794","article-title":"Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3","volume":"270","author":"Thomis","year":"1995","journal-title":"Science"},{"key":"2019052308203693500_key339-B8","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/377065a0","article-title":"Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)","volume":"377","author":"Macchi","year":"1995","journal-title":"Nature"},{"key":"2019052308203693500_key339-B9","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1126\/science.270.5237.797","article-title":"Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development","volume":"270","author":"Russell","year":"1995","journal-title":"Science"},{"key":"2019052308203693500_key339-B10","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1074-7613(00)00054-6","article-title":"Partial impairment of cytokine responses in Tyk2-deficient mice","volume":"13","author":"Karaghiosoff","year":"2000","journal-title":"Immunity"},{"key":"2019052308203693500_key339-B11","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1056\/NEJMoa1112072","article-title":"Tofacitinib or adalimumab versus placebo in rheumatoid arthritis","volume":"367","author":"van Vollenhoven","year":"2012","journal-title":"N Engl J Med"},{"key":"2019052308203693500_key339-B12","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1056\/NEJMoa1608345","article-title":"Baricitinib versus placebo or adalimumab in rheumatoid arthritis","volume":"376","author":"Taylor","year":"2017","journal-title":"N Engl J Med"},{"key":"2019052308203693500_key339-B13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.7326\/0003-4819-159-4-201308200-00006","article-title":"Tofacitinib in combination with nonbiologic disease\u2010modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial","volume":"159","author":"Kremer","year":"2013","journal-title":"Ann Intern Med"},{"key":"2019052308203693500_key339-B14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/annrheumdis-2016-210094","article-title":"Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study","volume":"76","author":"Dougados","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2019052308203693500_key339-B15","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0140-6736(12)61424-X","article-title":"Tofacitinib (CP-690, 550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial","volume":"381","author":"Burmester","year":"2013","journal-title":"Lancet"},{"key":"2019052308203693500_key339-B16","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1056\/NEJMoa1507247","article-title":"Baricitinib in patients with refractory rheumatoid arthritis","volume":"374","author":"Genovese","year":"2016","journal-title":"N Engl J Med"},{"key":"2019052308203693500_key339-B17","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1056\/NEJMoa1310476","article-title":"Tofacitinib versus methotrexate in rheumatoid arthritis","volume":"370","author":"Lee","year":"2014","journal-title":"N Engl J Med"},{"key":"2019052308203693500_key339-B18","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/art.39953","article-title":"Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment","volume":"69","author":"Fleischmann","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B19","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMoa1109071","article-title":"Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis","volume":"367","author":"Fleischmann","year":"2012","journal-title":"N Engl J Med"},{"key":"2019052308203693500_key339-B20","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/art.37816","article-title":"Tofacitinib (CP-690, 550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study","volume":"65","author":"van der Heijde","year":"2013","journal-title":"Arthritis Rheum"},{"key":"2019052308203693500_key339-B21","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0140-6736(17)31618-5","article-title":"Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b\/4, double-blind, head-to-head, randomised controlled trial","volume":"390","author":"Fleischmann","year":"2017","journal-title":"Lancet"},{"key":"2019052308203693500_key339-B22","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1002\/art.39801","article-title":"A phase IIb study of ABT-494, a selective JAK-1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to anti-tumor necrosis factor therapy","volume":"68","author":"Kremer","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B23","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1002\/art.39808","article-title":"Efficacy and safety of ABT-494, a selective JAK-1 inhibitor, in a phase IIb study in patients with rheumatoid arthritis and an inadequate response to methotrexate","volume":"68","author":"Genovese","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B24","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1136\/annrheumdis-2016-210104","article-title":"Filgotinib (GLPG0634\/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1)","volume":"76","author":"Westhovens","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2019052308203693500_key339-B25","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1136\/annrheumdis-2016-210105","article-title":"Filgotinib (GLPG0634\/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2)","volume":"76","author":"Kavanaugh","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2019052308203693500_key339-B26","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/art.40054","article-title":"Peficitinib, a JAK inhibitor, in combination with limited conventional synthetic disease-modifying antirheumatic drugs in the treatment of moderate-to-severe rheumatoid arthritis","volume":"69","author":"Genovese","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B27","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1002\/art.39955","article-title":"Peficitinib, a JAK inhibitor, in the treatment of moderate-to-severe rheumatoid arthritis in patients with an inadequate response to methotrexate","volume":"69","author":"Kivitz","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B28","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/art.38949","article-title":"A randomized, double-blind, placebo-controlled, twelve-week, dose-ranging study of decernotinib, an oral selective JAK-3 inhibitor, as monotherapy in patients with active rheumatoid arthritis","volume":"67","author":"Fleischmann","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B29","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/art.39473","article-title":"VX-509 (decernotinib), an oral selective JAK-3 inhibitor, in combination with methotrexate in patients with rheumatoid arthritis","volume":"68","author":"Genovese","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B30","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1016\/S0140-6736(18)31115-2","article-title":"Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial","volume":"391","author":"Burmester","year":"2018","journal-title":"Lancet"},{"key":"2019052308203693500_key339-B31","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1016\/S0140-6736(18)31116-4","article-title":"Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial","volume":"391","author":"Genovese","year":"2018","journal-title":"Lancet"},{"key":"2019052308203693500_key339-B32","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s40744-018-0097-3","article-title":"Worldwide, 3-year, post-marketing surveillance experience with tofacitinib in rheumatoid arthritis","volume":"5","author":"Cohen","year":"2018","journal-title":"Rheumatol Ther"},{"key":"2019052308203693500_key339-B33","first-page":"1","article-title":"Safety of biologics in rheumatoid arthritis: data from randomized controlled trials and registries","volume":"9","author":"Codreanu","year":"2015","journal-title":"Biologics"},{"key":"2019052308203693500_key339-B34","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1136\/annrheumdis-2016-210457","article-title":"Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials","volume":"76","author":"Cohen","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2019052308203693500_key339-B35","first-page":"3","article-title":"Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 5.5 years: an updated integrated safety analysis. Presented at the ACR\/ARHP Annual Meeting","author":"Genovese","year":"2017","journal-title":"San Diego, CA, USA"},{"key":"2019052308203693500_key339-B36","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1002\/art.40189","article-title":"Herpes zoster and tofacitinib. Clinical outcomes and the risk of concomitant therapy","volume":"69","author":"Winthrop","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B37","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1002\/art.40187","article-title":"The safety and immunogenicity of live zoster vaccination in patients with rheumatoid arthritis before starting tofacitinib: a randomized phase II trial","volume":"69","author":"Winthrop","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B38","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1136\/annrheumdis-2016-209773","article-title":"Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs","volume":"76","author":"Strangfeld","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2019052308203693500_key339-B39","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1002\/art.39761","article-title":"Brief report: risk of gastrointestinal perforation among rheumatoid arthritis patients receiving tofacitinib, tocilizumab, or other biologic treatments","volume":"68","author":"Xie","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B40","first-page":"3","author":"Weinblatt","year":"2017"},{"key":"2019052308203693500_key339-B41","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.semarthrit.2008.08.002","article-title":"Treatment with infliximab plus methotrexate improves anemia in patients with rheumatoid arthritis independent of improvement in other clinical outcome measures-a pooled analysis from three large, multicenter, double-blind, randomized clinical trials","volume":"39","author":"Doyle","year":"2009","journal-title":"Semin Arthritis Rheum"},{"key":"2019052308203693500_key339-B42","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.semarthrit.2017.08.001","article-title":"Effectiveness of biologic and non-biologic antirheumatic drugs on anaemia markers in 153,788 patients with rheumatoid arthritis: new evidence from real-world data","volume":"47","author":"Paul","year":"2018","journal-title":"Semin Arthritis Rheum"},{"key":"2019052308203693500_key339-B43","doi-asserted-by":"crossref","first-page":"3536","DOI":"10.1182\/blood-2014-11-575357","article-title":"Emerging EPO and EPO receptor regulators and signal transducers","volume":"125","author":"Kuhrt","year":"2015","journal-title":"Blood"},{"key":"2019052308203693500_key339-B44","first-page":"8","author":"Smolen","year":"2016"},{"key":"2019052308203693500_key339-B45","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1093\/rheumatology\/kew329","article-title":"Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies","volume":"56","author":"Schulze-Koops","year":"2017","journal-title":"Rheumatology (Oxford)"},{"key":"2019052308203693500_key339-B46","year":"2017"},{"key":"2019052308203693500_key339-B47","year":"2017"},{"key":"2019052308203693500_key339-B48","first-page":"14","author":"Kremer","year":"2017"},{"key":"2019052308203693500_key339-B49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.semarthrit.2016.03.004","article-title":"Effects of tofacitinib and other DMARDs on lipid profiles in rheumatoid arthritis: implications for the rheumatologist","volume":"46","author":"Charles-Schoeman","year":"2016","journal-title":"Semin Arthritis Rheum"},{"key":"2019052308203693500_key339-B50","author":"McInnes","year":"2016"},{"key":"2019052308203693500_key339-B51","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.semarthrit.2016.05.014","article-title":"Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor","volume":"46","author":"Charles-Schoeman","year":"2016","journal-title":"Semin Arthritis Rheum"},{"key":"2019052308203693500_key339-B52","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/art.38974","article-title":"Potential mechanisms leading to the abnormal lipid profile in patients with rheumatoid arthritis versus healthy volunteers and reversal by tofacitinib","volume":"67","author":"Charles-Schoeman","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B53","doi-asserted-by":"crossref","first-page":"e000491","DOI":"10.1136\/rmdopen-2017-000491","article-title":"Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies","volume":"3","author":"Fleischmann","year":"2017","journal-title":"RMD Open"},{"key":"2019052308203693500_key339-B54","doi-asserted-by":"crossref","first-page":"R158","DOI":"10.1186\/ar4673","article-title":"Changes in serum creatinine in patients with active rheumatoid arthritis treated with tofacitinib: results from clinical trials","volume":"16","author":"Isaacs","year":"2014","journal-title":"Arthritis Res Ther"},{"key":"2019052308203693500_key339-B55","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1136\/annrheumdis-2014-206478","article-title":"Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate","volume":"74","author":"Keystone","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"2019052308203693500_key339-B56","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/030097401316909530","article-title":"Randomized, double-blind trial of anti-interferon-gamma antibodies in rheumatoid arthritis","volume":"30","author":"Sigidin","year":"2001","journal-title":"Scand J Rheumatol"},{"key":"2019052308203693500_key339-B57","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1136\/annrheumdis-2016-210624","article-title":"A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis","volume":"76","author":"Burmester","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2019052308203693500_key339-B58","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/art.40323","article-title":"A randomized phase IIb study of mavrilimumab and golimumab in rheumatoid arthritis","volume":"70","author":"Weinblatt","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"2019052308203693500_key339-B59","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.thromres.2014.03.042","article-title":"Role of a Janus kinase 2-dependent signaling pathway in platelet activation","volume":"133","author":"Lu","year":"2014","journal-title":"Thromb Res"}],"container-title":["Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/rheumatology\/article-pdf\/58\/6\/953\/28697447\/key339.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T08:46:37Z","timestamp":1558601197000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/rheumatology\/article\/58\/6\/953\/5224985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,1]]},"references-count":59,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,12,1]]},"published-print":{"date-parts":[[2019,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/rheumatology\/key339","relation":{},"ISSN":["1462-0324","1462-0332"],"issn-type":[{"value":"1462-0324","type":"print"},{"value":"1462-0332","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,6]]},"published":{"date-parts":[[2018,12,1]]}}}