{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:31:41Z","timestamp":1772166701424,"version":"3.50.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":31,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Rheumatol"],"DOI":"10.1186\/s41927-025-00611-x","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T15:33:28Z","timestamp":1767108808000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Add-on iguratimod or tacrolimus in methotrexate in patients with rheumatoid arthritis not achieving remission with methotrexate: a retrospective propensity score-matched study"],"prefix":"10.1186","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1900-4522","authenticated-orcid":false,"given":"Yuji","family":"Kishimoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Nakazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manami","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Kuranobu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"611_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/annrheumdis-2015-207524","volume":"75","author":"JS Smolen","year":"2016","unstructured":"Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75:3\u201315. https:\/\/doi.org\/10.1136\/annrheumdis-2015-207524.","journal-title":"Ann Rheum Dis"},{"key":"611_CR2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/ard-2022-223356","volume":"82","author":"JS Smolen","year":"2023","unstructured":"Smolen JS, Landew\u00e9 RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82:3\u201318. https:\/\/doi.org\/10.1136\/ard-2022-223356.","journal-title":"Ann Rheum Dis"},{"key":"611_CR3","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1093\/mr\/roaf006","volume":"35","author":"M Harigai","year":"2025","unstructured":"Harigai M, Kaneko Y, Tanaka E, et al. 2024 update of the Japan college of rheumatology clinical practice guidelines for the management of rheumatoid arthritis: secondary publication. Mod Rheumatol. 2025;35:387\u2013401. https:\/\/doi.org\/10.1093\/mr\/roaf006.","journal-title":"Mod Rheumatol"},{"key":"611_CR4","doi-asserted-by":"publisher","first-page":"e000993","DOI":"10.1136\/rmdopen-2019-000993","volume":"5","author":"K Chatzidionysiou","year":"2019","unstructured":"Chatzidionysiou K, Sfikakis PP. Low rates of remission with methotrexate monotherapy in rheumatoid arthritis: review of randomised controlled trials could point towards a paradigm shift. RMD Open. 2019;5:e000993. https:\/\/doi.org\/10.1136\/rmdopen-2019-000993.","journal-title":"RMD Open"},{"key":"611_CR5","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/j.jos.2023.03.020","volume":"29","author":"M Suzuki","year":"2024","unstructured":"Suzuki M, Asai S, Hara R, et al. Choice of and response to treatment in patients with early-diagnosed rheumatoid arthritis: Real-world data from an inception cohort in Japan (NICER-J). J Orthop Sci Off J Jpn Orthop Assoc. 2024;29:921\u20136. https:\/\/doi.org\/10.1016\/j.jos.2023.03.020.","journal-title":"J Orthop Sci Off J Jpn Orthop Assoc"},{"key":"611_CR6","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s40266-025-01195-4","volume":"42","author":"M Harigai","year":"2025","unstructured":"Harigai M, Sugihara T. Management of Late-Onset rheumatoid arthritis with Treat-to-Target strategy. Drugs Aging. 2025;42:413\u201333. https:\/\/doi.org\/10.1007\/s40266-025-01195-4.","journal-title":"Drugs Aging"},{"key":"611_CR7","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1093\/rheumatology\/keaa557","volume":"60","author":"K Thomas","year":"2021","unstructured":"Thomas K, Lazarini A, Kaltsonoudis E, et al. Incidence, risk factors and validation of the RABBIT score for serious infections in a cohort of 1557 patients with rheumatoid arthritis. Rheumatol Oxf Engl. 2021;60:2223\u201330. https:\/\/doi.org\/10.1093\/rheumatology\/keaa557.","journal-title":"Rheumatol Oxf Engl"},{"key":"611_CR8","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1016\/S0140-6736(12)60027-0","volume":"379","author":"RF van Vollenhoven","year":"2012","unstructured":"van Vollenhoven RF, Geborek P, Forslind K, et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet Lond Engl. 2012;379:1712\u201320. https:\/\/doi.org\/10.1016\/S0140-6736(12)60027-0.","journal-title":"Lancet Lond Engl"},{"key":"611_CR9","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3109\/14397595.2015.1059984","volume":"26","author":"H Matsuno","year":"2016","unstructured":"Matsuno H, Okada M, Sakai Y, et al. The usefulness of a new triple combination treatment utilizing methotrexate, salazosulfapyridine, and bucillamine in rheumatoid arthritis. Mod Rheumatol. 2016;26:51\u20136. https:\/\/doi.org\/10.3109\/14397595.2015.1059984.","journal-title":"Mod Rheumatol"},{"key":"611_CR10","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1007\/s10165-012-0724-8","volume":"23","author":"N Ishiguro","year":"2013","unstructured":"Ishiguro N, Yamamoto K, Katayama K, et al. Concomitant Iguratimod therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate: a randomized, double-blind, placebo-controlled trial. Mod Rheumatol. 2013;23:430\u20139. https:\/\/doi.org\/10.1007\/s10165-012-0724-8.","journal-title":"Mod Rheumatol"},{"key":"611_CR11","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1007\/s10165-011-0425-8","volume":"21","author":"S Kawai","year":"2011","unstructured":"Kawai S, Takeuchi T, Yamamoto K, et al. Efficacy and safety of additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to DMARDs\u2013a multicenter, double-blind, parallel-group trial. Mod Rheumatol. 2011;21:458\u201368. https:\/\/doi.org\/10.1007\/s10165-011-0425-8.","journal-title":"Mod Rheumatol"},{"key":"611_CR12","doi-asserted-by":"publisher","first-page":"410","DOI":"10.3109\/14397595.2013.843756","volume":"24","author":"M Hara","year":"2014","unstructured":"Hara M, Ishiguro N, Katayama K, et al. Safety and efficacy of combination therapy of Iguratimod with methotrexate for patients with active rheumatoid arthritis with an inadequate response to methotrexate: an open-label extension of a randomized, double-blind, placebo-controlled trial. Mod Rheumatol. 2014;24:410\u20138. https:\/\/doi.org\/10.3109\/14397595.2013.843756.","journal-title":"Mod Rheumatol"},{"key":"611_CR13","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1093\/mr\/roac060","volume":"33","author":"Y Nozaki","year":"2023","unstructured":"Nozaki Y, Oribe M, Tomita D, et al. Iguratimod versus Salazosulfapyridine in rheumatoid arthritis patients with an inadequate response to methotrexate: adjusted with propensity score matching. Mod Rheumatol. 2023;33:472\u201380. https:\/\/doi.org\/10.1093\/mr\/roac060.","journal-title":"Mod Rheumatol"},{"key":"611_CR14","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1136\/ard.2011.149765","volume":"70","author":"DT Felson","year":"2011","unstructured":"Felson DT, Smolen JS, Wells G, et al. American college of Rheumatology\/European league against rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis. 2011;70:404\u201313. https:\/\/doi.org\/10.1136\/ard.2011.149765.","journal-title":"Ann Rheum Dis"},{"key":"611_CR15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1080\/14397595.2018.1472358","volume":"29","author":"H Kameda","year":"2019","unstructured":"Kameda H, Fujii T, Nakajima A, et al. Japan college of rheumatology guideline for the use of methotrexate in patients with rheumatoid arthritis. Mod Rheumatol. 2019;29:31\u201340. https:\/\/doi.org\/10.1080\/14397595.2018.1472358.","journal-title":"Mod Rheumatol"},{"key":"611_CR16","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1002\/art.27584","volume":"62","author":"D Aletaha","year":"2010","unstructured":"Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American college of Rheumatology\/European league against rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569\u201381. https:\/\/doi.org\/10.1002\/art.27584.","journal-title":"Arthritis Rheum"},{"key":"611_CR17","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1136\/ard-2022-223413","volume":"82","author":"P Studenic","year":"2023","unstructured":"Studenic P, Aletaha D, de Wit M, et al. American college of Rheumatology\/EULAR remission criteria for rheumatoid arthritis: 2022 revision. Ann Rheum Dis. 2023;82:74\u201380. https:\/\/doi.org\/10.1136\/ard-2022-223413.","journal-title":"Ann Rheum Dis"},{"key":"611_CR18","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1002\/acr.22456","volume":"67","author":"BR England","year":"2015","unstructured":"England BR, Sayles H, Mikuls TR, et al. Validation of the rheumatic disease comorbidity index. Arthritis Care Res Hoboken. 2015;67:865\u201372. https:\/\/doi.org\/10.1002\/acr.22456.","journal-title":"Arthritis Care Res Hoboken"},{"key":"611_CR19","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/00273171.2011.568786","volume":"46","author":"PC Austin","year":"2011","unstructured":"Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res. 2011;46:399\u2013424. https:\/\/doi.org\/10.1080\/00273171.2011.568786.","journal-title":"Multivar Behav Res"},{"key":"611_CR20","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bmt.2012.244","volume":"48","author":"Y Kanda","year":"2013","unstructured":"Kanda Y. Investigation of the freely available easy-to-use software EZR for medical statistics. Bone Marrow Transpl. 2013;48:452\u20138. https:\/\/doi.org\/10.1038\/bmt.2012.244.","journal-title":"Bone Marrow Transpl"},{"key":"611_CR21","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez461","author":"E Nikiphorou","year":"2019","unstructured":"Nikiphorou E, Norton SJ, Carpenter L, et al. Remission vs low disease activity: function, quality of life and structural outcomes in the early rheumatoid arthritis study and network. Rheumatol Oxf. 2019. https:\/\/doi.org\/10.1093\/rheumatology\/kez461.","journal-title":"Rheumatol Oxf"},{"key":"611_CR22","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/s13075-023-03176-7","volume":"25","author":"A Ruyssen-Witrand","year":"2023","unstructured":"Ruyssen-Witrand A, Guernec G, Dupont J, et al. Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity. Arthritis Res Ther. 2023;25:207. https:\/\/doi.org\/10.1186\/s13075-023-03176-7.","journal-title":"Arthritis Res Ther"},{"key":"611_CR23","doi-asserted-by":"publisher","first-page":"1150661","DOI":"10.3389\/fimmu.2023.1150661","volume":"14","author":"Z Long","year":"2023","unstructured":"Long Z, Zeng L, He Q, et al. Research progress on the clinical application and mechanism of Iguratimod in the treatment of autoimmune diseases and rheumatic diseases. Front Immunol. 2023;14:1150661. https:\/\/doi.org\/10.3389\/fimmu.2023.1150661.","journal-title":"Front Immunol"},{"key":"611_CR24","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/s41584-020-0373-9","volume":"16","author":"BN Cronstein","year":"2020","unstructured":"Cronstein BN, Aune TM. Methotrexate and its mechanisms of action in inflammatory arthritis. Nat Rev Rheumatol. 2020;16:145\u201354. https:\/\/doi.org\/10.1038\/s41584-020-0373-9.","journal-title":"Nat Rev Rheumatol"},{"key":"611_CR25","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1177\/1759720X11419038","volume":"3","author":"S Dutta","year":"2011","unstructured":"Dutta S, Ahmad Y. The efficacy and safety of tacrolimus in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2011;3:283\u201391. https:\/\/doi.org\/10.1177\/1759720X11419038.","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"611_CR26","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1007\/s10165-012-0745-3","volume":"23","author":"M Kitahama","year":"2013","unstructured":"Kitahama M, Nakajima A, Inoue E, et al. Efficacy of adjunct tacrolimus treatment in patients with rheumatoid arthritis with inadequate responses to methotrexate. Mod Rheumatol. 2013;23:788\u201393. https:\/\/doi.org\/10.1007\/s10165-012-0745-3.","journal-title":"Mod Rheumatol"},{"key":"611_CR27","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s10165-008-0071-y","volume":"18","author":"Y Morita","year":"2008","unstructured":"Morita Y, Sasae Y, Sakuta T, et al. Efficacy of low-dose tacrolimus added to methotrexate in patients with rheumatoid arthritis in japan: a retrospective study. Mod Rheumatol. 2008;18:379\u201384. https:\/\/doi.org\/10.1007\/s10165-008-0071-y.","journal-title":"Mod Rheumatol"},{"key":"611_CR28","doi-asserted-by":"publisher","first-page":"105053","DOI":"10.1016\/j.jbspin.2020.07.002","volume":"88","author":"JA Singh","year":"2021","unstructured":"Singh JA, Tornberg H, Goodman SM. Pop a pill or give myself a shot? Patient perspectives of disease-modifying anti-rheumatic drug choice for rheumatoid arthritis. Joint Bone Spine. 2021;88:105053. https:\/\/doi.org\/10.1016\/j.jbspin.2020.07.002.","journal-title":"Joint Bone Spine"},{"key":"611_CR29","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3109\/14397595.2013.854074","volume":"24","author":"T Takeuchi","year":"2014","unstructured":"Takeuchi T, Kawai S, Yamamoto K, et al. Post-marketing surveillance of the safety and effectiveness of tacrolimus in 3,267 Japanese patients with rheumatoid arthritis. Mod Rheumatol. 2014;24:8\u201316. https:\/\/doi.org\/10.3109\/14397595.2013.854074.","journal-title":"Mod Rheumatol"},{"key":"611_CR30","doi-asserted-by":"publisher","first-page":"e0253513","DOI":"10.1371\/journal.pone.0253513","volume":"16","author":"K Shibata","year":"2021","unstructured":"Shibata K, Yoshimura A, Ikeuchi S, Ishii M. Effectiveness of drug safety measures for reducing the incidence of adverse drug reactions: Post-hoc analysis of data from all-case surveillance of Iguratimod using generalized estimating equations. PLoS ONE. 2021;16:e0253513. https:\/\/doi.org\/10.1371\/journal.pone.0253513.","journal-title":"PLoS ONE"}],"container-title":["BMC Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41927-025-00611-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41927-025-00611-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41927-025-00611-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:57:31Z","timestamp":1769785051000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s41927-025-00611-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,30]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["611"],"URL":"https:\/\/doi.org\/10.1186\/s41927-025-00611-x","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-8026013\/v1","asserted-by":"object"}]},"ISSN":["2520-1026"],"issn-type":[{"value":"2520-1026","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,30]]},"assertion":[{"value":"4 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Institutional Review Board of Tottori Red Cross Hospital (Approval No. 262) and conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12"}}