{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:17:43Z","timestamp":1783423063759,"version":"3.54.6"},"reference-count":22,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Musculoskeletal"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Tocilizumab (TCZ), an interleukin-6 receptor inhibitor, is effective for moderate to severe rheumatoid arthritis (RA). However, maintaining remission after TCZ withdrawal remains challenging, and the treatment duration required before discontinuation to minimize relapse risk is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To identify a TCZ treatment-duration threshold before withdrawal that is associated with a lower risk of relapse in patients with RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>This was a retrospective study including 97 patients with RA who discontinued intravenous TCZ after stable disease control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We retrospectively analyzed 97 RA patients who achieved remission or low disease activity prior to TCZ withdrawal. The primary outcome was relapse within 12\u2009months post-discontinuation. Cox proportional hazards regression identified independent predictors, while restricted cubic spline (RCS) modeling assessed non-linear associations between treatment duration and relapse risk. A simplified risk stratification tool was developed and internally validated using bootstrap resampling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Among 97 patients with RA who discontinued TCZ after stable disease control, most were biologic-na\u00efve (98.9%), the mean disease duration was 72.9\u2009\u00b1\u200952.7\u2009months, and concomitant methotrexate and hydroxychloroquine were used in 73.2% and 47.4% of patients, respectively. During the 12-month follow-up, 54 patients (55.7%) relapsed. TCZ treatment duration was an independent protective factor (adjusted HR\u2009=\u20090.892\u2009per month,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.002), whereas anti-citrullinated protein antibody (ACPA) positivity was associated with increased relapse risk (adjusted HR\u2009=\u20092.122,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.031). RCS analysis demonstrated an L-shaped non-linear relationship, identifying an empirically derived duration threshold at approximately 200\u2009days associated with lower relapse risk. A simplified score assigning 1 point each for ACPA positivity and TCZ duration\u2009&lt;\u2009200\u2009days stratified patients into low- (0 points), intermediate- (1 point), and high-risk (2 points) groups, with relapse rates of 27.3%, 53.8%, and 91.7%, respectively; the model showed acceptable discrimination (AUC\u2009=\u20090.76).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Longer TCZ treatment duration and ACPA negativity were associated with a lower risk of relapse after TCZ withdrawal. An approximately 200-day treatment duration may serve as a clinically informative threshold for risk-stratified withdrawal decisions in routine practice, although disease control after withdrawal should be interpreted in the context of ongoing background therapy rather than confirmed drug-free remission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1759720x261464266","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T12:17:44Z","timestamp":1783167464000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Restricted cubic spline analysis of treatment duration before tocilizumab withdrawal and relapse risk in rheumatoid arthritis"],"prefix":"10.1177","volume":"18","author":[{"given":"Houhui","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0110-4912","authenticated-orcid":false,"given":"Rui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwaizheng Street, Donghu District, Nanchang, Jiangxi 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01525-8"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1470488"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2022.102308"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-016-3490-8"},{"issue":"5","key":"e_1_3_4_6_2","article-title":"Down-titration and discontinuation strategies of tumour necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity","volume":"5","author":"Verhoef LM","year":"2019","unstructured":"Verhoef LM, van den Bemt BJ, van der Maas A, et al. Down-titration and discontinuation strategies of tumour necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity. Cochrane Database Syst Rev 2019; 5(5): Cd010455.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.2024-0383"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214981"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2023.2157814"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41927-019-0109-0"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60250-0"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2024-092478"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00010"},{"key":"e_1_3_4_14_2","article-title":"Tocilizumab vs prednisone in established rheumatoid arthritis patients (TOPIRA): an investigator-initiated randomised clinical trial","volume":"65","author":"Fadaei S","year":"2025","unstructured":"Fadaei S, van der Leeuw MS, Linn-Rasker SP, et al. Tocilizumab vs prednisone in established rheumatoid arthritis patients (TOPIRA): an investigator-initiated randomised clinical trial. Rheumatology (Oxford) 2025; 65: keaf591.","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.13103"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.153"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-222784"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keae196"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0627-z"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114015"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kev006"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-0927-z"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab276"}],"container-title":["Therapeutic Advances in Musculoskeletal Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1759720X261464266","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1759720X261464266","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1759720X261464266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:46:37Z","timestamp":1783421197000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1759720X261464266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":22,"alternative-id":["10.1177\/1759720X261464266"],"URL":"https:\/\/doi.org\/10.1177\/1759720x261464266","relation":{},"ISSN":["1759-720X","1759-7218"],"issn-type":[{"value":"1759-720X","type":"print"},{"value":"1759-7218","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"article-number":"1759720X261464266"}}