{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T04:12:56Z","timestamp":1769746376917,"version":"3.49.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","funder":[{"name":"Janssen Pharmaceutical K.K."},{"name":"Glaxo SmithKline"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s13075-018-1536-9","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T11:54:15Z","timestamp":1520423655000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Sirukumab in rheumatoid arthritis refractory to sulfasalazine or methotrexate: a randomized phase 3 safety and efficacy study in Japanese patients"],"prefix":"10.1186","volume":"20","author":[{"given":"Tsutomu","family":"Takeuchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayoshi","family":"Harigai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Tamamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshifumi","family":"Ukyo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshikazu","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,3,7]]},"reference":[{"issue":"10","key":"1536_CR1","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1038\/nrrheum.2009.181","volume":"5","author":"PC Taylor","year":"2009","unstructured":"Taylor PC, Feldmann M. Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. Nat Rev Rheumatol. 2009;5(10):578\u201382.","journal-title":"Nat Rev Rheumatol"},{"issue":"4","key":"1536_CR2","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1111\/j.1476-5381.2010.01099.x","volume":"162","author":"D Mewar","year":"2011","unstructured":"Mewar D, Wilson AG. Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors. Br J Pharmacol. 2011;162(4):785\u201391.","journal-title":"Br J Pharmacol"},{"issue":"11","key":"1536_CR3","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1002\/eji.1830181122","volume":"18","author":"T Hirano","year":"1988","unstructured":"Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B, et al. Excessive production of interleukin 6\/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol. 1988;18(11):1797\u2013802.","journal-title":"Eur J Immunol"},{"issue":"9","key":"1536_CR4","doi-asserted-by":"publisher","first-page":"2817","DOI":"10.1002\/art.22033","volume":"54","author":"RN Maini","year":"2006","unstructured":"Maini RN, Taylor PC, Szechinski J, Pavelka K, Broll J, Balint G, et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 2006;54(9):2817\u201329. \n                    https:\/\/doi.org\/10.1002\/art.22033","journal-title":"Arthritis Rheum"},{"issue":"10","key":"1536_CR5","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1136\/ard.2008.092866","volume":"68","author":"N Nishimoto","year":"2009","unstructured":"Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J. Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis. 2009;68(10):1580\u20134.","journal-title":"Ann Rheum Dis"},{"issue":"9617","key":"1536_CR6","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/S0140-6736(08)60453-5","volume":"371","author":"JS Smolen","year":"2008","unstructured":"Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371(9617):987\u201397.","journal-title":"Lancet"},{"issue":"2","key":"1536_CR7","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1111\/j.1365-2125.2011.03964.x","volume":"72","author":"Z Xu","year":"2011","unstructured":"Xu Z, Bouman-Thio E, Comisar C, Frederick B, Van Hartingsveldt B, Marini JC, et al. Pharmacokinetics, pharmacodynamics and safety of a human anti-IL-6 monoclonal antibody (sirukumab) in healthy subjects in a first-in-human study. Br J Clin Pharmacol. 2011;72(2):270\u201381.","journal-title":"Br J Clin Pharmacol"},{"issue":"9","key":"1536_CR8","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1136\/annrheumdis-2013-205137","volume":"73","author":"JS Smolen","year":"2014","unstructured":"Smolen JS, Weinblatt ME, Sheng S, Zhuang Y, Hsu B. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2014;73(9):1616\u201325.","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"1536_CR9","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/art.1780370304","volume":"37","author":"JM Kremer","year":"1994","unstructured":"Kremer JM, Alarcon GS, Lightfoot RW Jr, Willkens RF, Furst DE, Williams HJ, et al. Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum. 1994;37(3):316\u201328.","journal-title":"Arthritis Rheum"},{"issue":"8","key":"1536_CR10","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1002\/acr.22294","volume":"66","author":"G Schmajuk","year":"2014","unstructured":"Schmajuk G, Miao Y, Yazdany J, Boscardin WJ, Daikh DI, Steinman MA. Identification of risk factors for elevated transaminases in methotrexate users through an electronic health record. Arthritis Care Res (Hoboken). 2014;66(8):1159\u201366.","journal-title":"Arthritis Care Res (Hoboken)"},{"issue":"12","key":"1536_CR11","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1136\/annrheumdis-2017-211328","volume":"76","author":"T Takeuchi","year":"2017","unstructured":"Takeuchi T, Thorne C, Karpouzas G, Sheng S, Xu W, Rao R, et al. Sirukumab for rheumatoid arthritis: the phase III SIRROUND-D study. Ann Rheum Dis. 2017;76(12):2001\u201308.","journal-title":"Ann Rheum Dis"},{"issue":"10075","key":"1536_CR12","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/S0140-6736(17)30401-4","volume":"389","author":"D Aletaha","year":"2017","unstructured":"Aletaha D, Bingham CO 3rd, Tanaka Y, Agarwal P, Kurrasch R, Tak PP, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study. Lancet. 2017;389(10075):1206\u201317.","journal-title":"Lancet"},{"issue":"6","key":"1536_CR13","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1080\/14712598.2017.1315099","volume":"17","author":"E Pelechas","year":"2017","unstructured":"Pelechas E, Voulgari PV, Drosos AA. Sirukumab: a promising therapy for rheumatoid arthritis. Expert Opin Biol Ther. 2017;17(6):755\u201363.","journal-title":"Expert Opin Biol Ther"},{"issue":"9","key":"1536_CR14","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1136\/annrheumdis-2012-201796","volume":"72","author":"T Takeuchi","year":"2013","unstructured":"Takeuchi T, Harigai M, Tanaka Y, Yamanaka H, Ishiguro N, Yamamoto K, et al. Golimumab monotherapy in Japanese patients with active rheumatoid arthritis despite prior treatment with disease-modifying antirheumatic drugs: results of the phase 2\/3, multicentre, randomised, double-blind, placebo-controlled GO-MONO study through 24 weeks. Ann Rheum Dis. 2013;72(9):1488\u201395.","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"1536_CR15","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1136\/annrheumdis-2013-204760","volume":"73","author":"MC Genovese","year":"2014","unstructured":"Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B, et al. Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised phase IIb study. Ann Rheum Dis. 2014;73(9):1607\u201315.","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"1536_CR16","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1136\/annrheumdis-2013-204405","volume":"73","author":"TW Huizinga","year":"2014","unstructured":"Huizinga TW, Fleischmann RM, Jasson M, Radin AR, van Adelsberg J, Fiore S, et al. Sarilumab, a fully human monoclonal antibody against IL-6R\u03b1 in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014;73(9):1626\u201334.","journal-title":"Ann Rheum Dis"},{"issue":"10","key":"1536_CR17","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.1002\/art.39249","volume":"67","author":"ME Weinblatt","year":"2015","unstructured":"Weinblatt ME, Mease P, Mysler E, Takeuchi T, Drescher E, Berman A, et al. The efficacy and safety of subcutaneous clazakizumab in patients with moderate-to-severe rheumatoid arthritis and an inadequate response to methotrexate: results from a multinational, phase IIb, randomized, double-blind, placebo\/active-controlled, dose-ranging study. Arthritis Rheumatol. 2015;67(10):2591\u2013600.","journal-title":"Arthritis Rheumatol"},{"issue":"7","key":"1536_CR18","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1136\/annrheumdis-2011-200704","volume":"71","author":"P Mease","year":"2012","unstructured":"Mease P, Strand V, Shalamberidze L, Dimic A, Raskina T, Xu L-A, et al. A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate. Ann Rheum Dis. 2012;71(7):1183\u201389.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"1536_CR19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1136\/annrheumdis-2013-203523","volume":"73","author":"GR Burmester","year":"2014","unstructured":"Burmester GR, Rubbert-Roth A, Cantagrel A, Hall S, Leszczynski P, Feldman D, et al. A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe rheumatoid arthritis (SUMMACTA study). Ann Rheum Dis. 2014;73(1):69\u201374.","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"1536_CR20","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1002\/acr.22110","volume":"66","author":"A Ogata","year":"2014","unstructured":"Ogata A, Tanimura K, Sugimoto T, Inoue H, Urata Y, Matsubara T, et al. Phase III study of the efficacy and safety of subcutaneous versus intravenous tocilizumab monotherapy in patients with rheumatoid arthritis. Arthritis Care Res. 2014;66(3):344\u201354.","journal-title":"Arthritis Care Res"}],"container-title":["Arthritis Research & Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-018-1536-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:23:05Z","timestamp":1551918185000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-018-1536-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,7]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["1536"],"URL":"https:\/\/doi.org\/10.1186\/s13075-018-1536-9","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,7]]},"assertion":[{"value":"14 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the institutional review board (Keio University Hospital) of the lead investigator (TT) and by the institutional review boards of each of the 20 other participating study sites. The study was conducted in accordance with the Declaration of Helsinki consistent with Good Clinical Practices and applicable regulatory requirements. All participants provided written informed consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"TT has received research grants from Astellas Pharma, Bristol-Myers K.K., Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Eisai Co. Ltd, Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd, Teijin Pharma Ltd, AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co. Ltd and SymBio Pharmaceuticals Ltd; has received consulting fees from Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co. Ltd, Bristol-Myers K.K. and Nippon Kayaku Co. Ltd; and has received speaking fees from AbbVie GK, Bristol-Myers K.K., Chugai Pharmaceutical Co. Ltd, Eisai Co. Ltd, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd, Astellas Pharma, Daiichi Sankyo Co. Ltd, Celtrion and Nippon Kayaku Co. Ltd.HY has received research grants from AbbVie, Asahi Kasei, Astellas, AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, GlaxoSmithKline, Janssen Pharmaceutical Product, L.P., Mitsubishi Tanabe, MSD, Nippon Kayaku, Pfizer Inc., Santen, Taisho Toyama, Takeda and Teijin; has received consulting fees from AbbVie, Astellas, AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Nippon Kayaku, Pfizer Inc., Takeda and Teijin; and has served on a speakers\u2019 bureau for AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Mitsubishi Tanabe, Pfizer Inc., Takeda and Teijin.MH has received research grants from AbbVie Japan, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Ono Pharmaceuticals, Santen Pharmaceutical, Takeda Pharmaceutical, UCB Japan and Teijin Pharma; and has received consulting fees from AbbVie Japan, Janssen Pharma, Chugai Pharmaceutical, Teijin Pharma, Eli Lilly Japan and Zenyaku Kogyo.YT has received research grants from Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie and Eisai; and has received consulting fees from Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi Kasei, YL Biologics, Sanofi, Janssen, Eli Lilly and GlaxoSmithKline.RT, YK, YU and TN are employees of Janssen Pharmaceutical K.K.BH is an employee and stockholder of Johnson & Johnson.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"42"}}