{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:43:36Z","timestamp":1765889016660,"version":"3.37.3"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To investigate the efficacy and safety of hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients with active RA, despite conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), were recruited. HCQ was administered for 24\u2009weeks, in addition to prior treatment. The primary end-point was the proportion of patients achieving American College of Rheumatology (ACR) 20 at Week 24, compared to that of a propensity score\u2013matched historical control group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Sixty patients were enrolled and administered HCQ. We also identified 276 patients as candidates for the historical control group. Propensity score matching yielded 46 patients in each group. The proportion of patients achieving ACR20 at Week 24 was significantly higher in the HCQ group than in the control group (54.4% vs. 28.3%, P\u2009=\u2009.007). The proportion of patients achieving ACR50 and ACR70 at Week 24 were also higher in the HCQ group than in the control group (ACR50, 30.4% vs. 4.3%, P\u2009=\u2009.006; ACR70, 17.4% vs. 0%, P\u2009=\u2009.005). Neither HCQ retinopathy nor any new safety signal was observed during the study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The addition of HCQ to csDMARDs was effective, with no new safety signal in patients with RA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/mr\/roac153","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T13:19:10Z","timestamp":1670591950000},"page":"50-59","source":"Crossref","is-referenced-by-count":3,"title":["Clinical and immunological effects of hydroxychloroquine in patients with active rheumatoid arthritis despite antirheumatic treatment"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5167-0715","authenticated-orcid":false,"given":"Hiroshi","family":"Takei","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Takanashi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotaro","family":"Otomo","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan"},{"name":"Otomo Rheumatology Clinic , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironari","family":"Hanaoka","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan"},{"name":"Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine , Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Abe","sequence":"additional","affiliation":[{"name":"School of Data Science, Yokohama City University , Yokohama, Japan"},{"name":"Biostatistics, Clinical and Translational Research Center, Keio University School of Medicine , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan"},{"name":"Saitama Medical University , Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"2024061306505866100_R1","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and management of rheumatoid arthritis: a review","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA"},{"key":"2024061306505866100_R2","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"2024061306505866100_R3","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1002\/art.21405","article-title":"Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial","volume":"52","author":"Goekoop-Ruiterman","year":"2005","journal-title":"Arthritis Rheum"},{"key":"2024061306505866100_R4","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1002\/1529-0131(200009)43:9<1927::AID-ANR3>3.0.CO;2-B","article-title":"The course of radiologic damage during the first six years of rheumatoid arthritis","volume":"43","author":"Hulsmans","year":"2000","journal-title":"Arthritis Rheum"},{"key":"2024061306505866100_R5","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/rheumatology\/kem257","article-title":"Clinical identification and treatment of a rapidly progressing disease state in patients with rheumatoid arthritis","volume":"47","author":"Emery","year":"2008","journal-title":"Rheumatology (Oxford)"},{"key":"2024061306505866100_R6","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N Engl J Med"},{"key":"2024061306505866100_R7","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.2169\/internalmedicine.53.2834","article-title":"A paradigm shift in rheumatoid arthritis over the past decade","volume":"53","author":"Kaneko","year":"2014","journal-title":"Intern Med"},{"key":"2024061306505866100_R8","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"2024061306505866100_R9","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/art.40018","article-title":"Effects of hydroxychloroquine in patients with cutaneous lupus erythematosus: a multicenter, double-blind, randomized, parallel-group trial","volume":"69","author":"Yokogawa","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2024061306505866100_R10","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u2018EZR\u2019 for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant"},{"key":"2024061306505866100_R11","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1002\/(SICI)1097-0258(19981015)17:19<2265::AID-SIM918>3.0.CO;2-B","article-title":"Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group","volume":"17","author":"D\u2019Agostino","year":"1998","journal-title":"Stat Med"},{"key":"2024061306505866100_R12","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1136\/annrheumdis-2015-207784","article-title":"Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching","volume":"75","author":"Kubo","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"2024061306505866100_R13","article-title":"Antimalarials for treating rheumatoid arthritis","author":"Suarez-Almazor","year":"2000","journal-title":"Cochrane Database Syst Rev"},{"key":"2024061306505866100_R14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0002-9343(99)80399-4","article-title":"A randomized trial of hydroxychloroquine in early rheumatoid arthritis: the HERA study","volume":"98","year":"1995","journal-title":"Am J Med"},{"key":"2024061306505866100_R15","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1136\/ard.52.10.711","article-title":"Hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis: a randomised double blind trial","volume":"52","author":"Faarvang","year":"1993","journal-title":"Ann Rheum Dis"},{"key":"2024061306505866100_R16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/acr.23826","article-title":"Clinical and structural efficacy of hydroxychloroquine in rheumatoid arthritis: a systematic review","volume":"72","author":"Rempenault","year":"2020","journal-title":"Arthritis Care Res"},{"key":"2024061306505866100_R17","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrrheum.2015.8","article-title":"Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges","volume":"11","author":"Smolen","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"2024061306505866100_R18","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nrrheum.2010.154","article-title":"The Japanese experience with biologic therapies for rheumatoid arthritis","volume":"6","author":"Takeuchi","year":"2010","journal-title":"Nat Rev Rheumatol"},{"key":"2024061306505866100_R19","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/rheumatology\/ker356","article-title":"Effectiveness of sulfasalazine and methotrexate in 1102 DMARD-naive patients with early RA","volume":"51","author":"Lie","year":"2012","journal-title":"Rheumatology (Oxford)"},{"key":"2024061306505866100_R20","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/14397595.2017.1332471","article-title":"Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): post-marketing surveillance in Japan","volume":"28","author":"Takeuchi","year":"2018","journal-title":"Mod Rheumatol"},{"key":"2024061306505866100_R21","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1080\/14397595.2016.1265695","article-title":"Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan","volume":"27","author":"Mimori","year":"2017","journal-title":"Mod Rheumatol"},{"key":"2024061306505866100_R22","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1056\/NEJM199605163342002","article-title":"Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications","volume":"334","author":"O\u2019Dell","year":"1996","journal-title":"N Engl J Med"},{"key":"2024061306505866100_R23","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1002\/art.34498","article-title":"A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of early aggressive rheumatoid arthritis trial","volume":"64","author":"Moreland","year":"2012","journal-title":"Arthritis Rheum"},{"key":"2024061306505866100_R24","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1016\/S0140-6736(12)60027-0","article-title":"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","volume":"379","author":"van Vollenhoven","year":"2012","journal-title":"Lancet"},{"key":"2024061306505866100_R25","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/art.23913","article-title":"Use of nonbiologic disease-modifying antirheumatic drugs and risk of infection in patients with rheumatoid arthritis","volume":"59","author":"Lacaille","year":"2008","journal-title":"Arthritis Rheum"},{"key":"2024061306505866100_R26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.autrev.2008.05.001","article-title":"DMARDs and infections in rheumatoid arthritis","volume":"8","author":"Caporali","year":"2008","journal-title":"Autoimmun Rev"},{"key":"2024061306505866100_R27","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.jaad.2019.04.068","article-title":"Adverse cutaneous drug reactions with antimalarials in cutaneous lupus and dermatomyositis: a retrospective cohort study","volume":"81","author":"Gonzalez","year":"2019","journal-title":"J Am Acad Dermatol"},{"key":"2024061306505866100_R28","first-page":"297","article-title":"Nationwide product registry for hydroxychloroquine in Japanese patients with cutaneous and systemic lupus erythematosus (in Japanese)","volume":"41","author":"Yamada","year":"2020","journal-title":"Ther Res"},{"key":"2024061306505866100_R29","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1007\/s10067-013-2309-0","article-title":"Reduction of plasma IL-6 but not TNF-\u03b1 by methotrexate in patients with early rheumatoid arthritis: a potential biomarker for radiographic progression","volume":"32","author":"Nishina","year":"2013","journal-title":"Clin Rheumatol"},{"key":"2024061306505866100_R30","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-015-0526-4","article-title":"Peripheral blood CD4(+)CD25(+)CD127(low) regulatory T cells are significantly increased by tocilizumab treatment in patients with rheumatoid arthritis: increase in regulatory T cells correlates with clinical response","volume":"17","author":"Kikuchi","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"2024061306505866100_R31","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.3899\/jrheum.150644","article-title":"Altered natural killer cell subsets in seropositive arthralgia and early rheumatoid arthritis are associated with autoantibody status","volume":"43","author":"Chalan","year":"2016","journal-title":"J Rheumatol"},{"key":"2024061306505866100_R32","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.622306","article-title":"The role of natural killer cells in autoimmune diseases","volume":"12","author":"Kucuksezer","year":"2021","journal-title":"Front Immunol"},{"key":"2024061306505866100_R33","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0049-0172(10)80012-5","article-title":"Mechanism of action of hydroxychloroquine as an antirheumatic drug","volume":"23","author":"Fox","year":"1993","journal-title":"Semin Arthritis Rheum"},{"key":"2024061306505866100_R34","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.4049\/jimmunol.1000702","article-title":"Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines","volume":"186","author":"Kuznik","year":"2011","journal-title":"J Immunol"},{"key":"2024061306505866100_R35","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.autrev.2017.11.009","article-title":"Targeting interferons and their pathways in systemic lupus erythematosus","volume":"17","author":"Chasset","year":"2018","journal-title":"Autoimmun Rev"}],"container-title":["Modern Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mr\/advance-article-pdf\/doi\/10.1093\/mr\/roac153\/54151979\/roac153.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/34\/1\/50\/58214237\/roac153.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/34\/1\/50\/58214237\/roac153.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T10:23:54Z","timestamp":1718274234000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mr\/article\/34\/1\/50\/6885349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12,9]]},"published-print":{"date-parts":[[2023,12,22]]}},"URL":"https:\/\/doi.org\/10.1093\/mr\/roac153","relation":{},"ISSN":["1439-7595","1439-7609"],"issn-type":[{"type":"print","value":"1439-7595"},{"type":"electronic","value":"1439-7609"}],"subject":[],"published-other":{"date-parts":[[2024,1,1]]},"published":{"date-parts":[[2022,12,9]]}}}