{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:50:10Z","timestamp":1792788610026,"version":"4.5.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Grant-in-Aid for Scientific Research","award":["20K08777"],"award-info":[{"award-number":["20K08777"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan\u2013Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0306714","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T13:41:07Z","timestamp":1720705267000},"page":"e0306714","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Real-world comparative study of drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis"],"prefix":"10.1371","volume":"19","author":[{"given":"Kenji","family":"Saito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honoka","family":"Ebina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Miyata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kanno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Sumichika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumpei","family":"Temmoku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Asano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzo","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1339-5622","authenticated-orcid":true,"given":"Kiyoshi","family":"Migita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"issue":"10055","key":"pone.0306714.ref001","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid 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New players in the field of immune-mediated diseases, beyond rheumatoid arthritis","volume":"58","author":"GE Fragoulis","year":"2019","journal-title":"Rheumatology (Oxford)"},{"issue":"7","key":"pone.0306714.ref017","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1002\/eji.202048922","article-title":"JAK inhibitors: Ten years after","volume":"51","author":"FR Spinelli","year":"2021","journal-title":"Eur J Immunol"},{"key":"pone.0306714.ref018","doi-asserted-by":"crossref","first-page":"110660","DOI":"10.1016\/j.intimp.2023.110660","article-title":"Current application status and structure-activity relationship of selective and non-selective JAK inhibitors in diseases","volume":"122","author":"T Li","year":"2023","journal-title":"Int Immunopharmacol"},{"issue":"7","key":"pone.0306714.ref019","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/annrheumdis-2020-219012","article-title":"JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib","volume":"80","author":"PG Traves","year":"2021","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"pone.0306714.ref020","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1136\/ard-2023-223850","article-title":"Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story","volume":"83","author":"M Bonelli","year":"2024","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"pone.0306714.ref021","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1136\/annrheumdis-2020-219699","article-title":"Efficacy and safety of tofacitinib versus baricitinib in patients with rheumatoid arthritis in real clinical practice: analyses with propensity score-based inverse probability of treatment weighting","volume":"80","author":"Y Miyazaki","year":"2021","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"pone.0306714.ref022","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2020-001174","article-title":"Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternative mode of action and tofacitinib in an observational cohort of patients with rheumatoid arthritis in Switzerland","volume":"6","author":"A Finckh","year":"2020","journal-title":"RMD Open"},{"issue":"3","key":"pone.0306714.ref023","doi-asserted-by":"crossref","first-page":"e063198","DOI":"10.1136\/bmjopen-2022-063198","article-title":"Discontinuation of tofacitinib and TNF inhibitors in patients with rheumatoid arthritis: analysis of pooled data from two registries in Canada","volume":"13","author":"M Movahedi","year":"2023","journal-title":"BMJ Open"},{"issue":"7","key":"pone.0306714.ref024","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/acr2.11432","article-title":"Time-Varying Association of Rheumatoid Arthritis Disease Activity to Subsequent Cardiovascular Risk","volume":"4","author":"K Yoshida","year":"2022","journal-title":"ACR Open Rheumatol"},{"issue":"2","key":"pone.0306714.ref025","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41584-023-01062-9","article-title":"Efficacy and safety of JAK inhibitors in rheumatoid arthritis: update for the practising clinician","volume":"20","author":"Z Szekanecz","year":"2024","journal-title":"Nat Rev Rheumatol"},{"issue":"4","key":"pone.0306714.ref026","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrrheum.2017.23","article-title":"The emerging safety profile of JAK inhibitors in rheumatic disease","volume":"13","author":"KL Winthrop","year":"2017","journal-title":"Nat Rev Rheumatol"},{"issue":"3","key":"pone.0306714.ref027","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/1744666X.2022.2039122","article-title":"Recent issues in JAK inhibitor safety: perspective for the clinician","volume":"18","author":"R. 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