{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:41:16Z","timestamp":1783960876967,"version":"3.55.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Chugai Pharmaceutical Co., Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder characterized by multifocal lymphadenopathy and systemic inflammatory symptoms. This single-arm, prospective, observational, postmarketing surveillance (UMIN000023071) assessed the real-world effectiveness and safety of tocilizumab in Japanese patients with MCD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with MCD received tocilizumab intravenous infusion 8\u00a0mg\/kg every 2\u00a0weeks for up to 3 years. Effectiveness outcomes included enlarged lymph node regression; improvement in laboratory findings, associated symptoms, and organ involvement; and change in corticosteroid doses. Safety was assessed through adverse events (AEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 342 patients were included. Tocilizumab was continued for &amp;gt;152\u00a0weeks in 70.1% of patients. After treatment, 58.9% of patients showed lymph node regression. Laboratory test values were improved, and most evaluable patients reported improvements in associated symptoms, including night sweats, anorexia, fever, and fatigue. Organ involvement, including pulmonary disease, rash, and hepatosplenomegaly, was \u2018improved\u2019 or \u2018stable\u2019 in more than half of evaluable patients. Tocilizumab treatment resulted in corticosteroid dose reduction. The most commonly reported AEs were infections and infestations; respiratory, thoracic, and mediastinal disorders; and gastrointestinal disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The effectiveness and safety of tocilizumab in Japanese patients with MCD was confirmed for up to 3\u00a0years, without new safety concerns.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/mr\/roaf100","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:26:26Z","timestamp":1760959586000},"page":"456-468","source":"Crossref","is-referenced-by-count":2,"title":["Effectiveness and safety of tocilizumab, an anti\u2013interleukin-6 receptor antibody, in 342 Japanese patients with multicentric Castleman disease: a 3-year, prospective, observational study"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8241-8010","authenticated-orcid":false,"given":"Norihiro","family":"Nishimoto","sequence":"first","affiliation":[{"name":"Osaka Rheumatology Clinic , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Murakami","sequence":"additional","affiliation":[{"name":"Osaka Rheumatology Clinic , Osaka ,","place":["Japan"]},{"name":"Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, The University of Osaka , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Johkoh","sequence":"additional","affiliation":[{"name":"Department of Radiology, Kansai Rosai Hospital , Hyogo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Hayashi","sequence":"additional","affiliation":[{"name":"National Hospital Organization Kinki Chuo Chest Medical Center , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Ohshima","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, National Hospital Organization, Osaka Minami Medical Center , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Mizuki","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy, The University of Osaka Hospital , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kakehi","sequence":"additional","affiliation":[{"name":"Safety Science 2 Department, Chugai Pharmaceutical Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Kawata","sequence":"additional","affiliation":[{"name":"Biometric Department, Chugai Pharmaceutical Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Safety Science 1 Department, Chugai Pharmaceutical Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misato","family":"Hashizume","sequence":"additional","affiliation":[{"name":"Oncology Lifecycle Management Department, Chugai Pharmaceutical Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Nakatsuka","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Safety Evaluation Committee of tocilizumab for Castleman disease","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"2026041500574313500_ref1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/1097-0142(195607\/08)9:4<822::AID-CNCR2820090430>3.0.CO;2-4","article-title":"Localized mediastinal lymphnode hyperplasia resembling thymoma","volume":"9","author":"Castleman","year":"1956","journal-title":"Cancer"},{"key":"2026041500574313500_ref2","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1182\/blood-2016-10-746933","article-title":"International, evidence-based consensus diagnostic criteria for HHV-8-negative\/idiopathic multicentric Castleman disease","volume":"129","author":"Fajgenbaum","year":"2017","journal-title":"Blood"},{"key":"2026041500574313500_ref3","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1182\/blood-2018-07-862334","article-title":"International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease","volume":"132","author":"Rhee","year":"2018","journal-title":"Blood"},{"key":"2026041500574313500_ref4","doi-asserted-by":"crossref","first-page":"292","DOI":"10.7861\/clinmedicine.15-3-292","article-title":"Malignant causes of fever of unknown origin","volume":"15","author":"Foggo","year":"2015","journal-title":"Clin Med (Lond)"},{"key":"2026041500574313500_ref5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/ajcp\/69.1.86","article-title":"Multicentric giant lymph node hyperplasia","volume":"69","author":"Gaba","year":"1978","journal-title":"Am J Clin Pathol"},{"key":"2026041500574313500_ref6","first-page":"636","article-title":"Multicentric Castleman\u2019s disease","volume":"20","author":"Peterson","year":"1993","journal-title":"Semin Oncol"},{"key":"2026041500574313500_ref7","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1182\/blood.V74.4.1360.1360","article-title":"Pathogenic significance of interleukin-6 (IL-6\/BSF-2) in Castleman\u2019s disease","volume":"74","author":"Yoshizaki","year":"1989","journal-title":"Blood"},{"key":"2026041500574313500_ref8","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1182\/bloodadvances.2021004441","article-title":"Epidemiology and treatment patterns of idiopathic multicentric Castleman disease in the era of IL-6-directed therapy","volume":"6","author":"Mukherjee","year":"2022","journal-title":"Blood Adv"},{"key":"2026041500574313500_ref9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3960\/jslrt.19021","article-title":"Epidemiological analysis of multicentric and unicentric Castleman disease and TAFRO syndrome in Japan","volume":"59","author":"Masaki","year":"2019","journal-title":"J Clin Exp Hematop"},{"key":"2026041500574313500_ref10","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1182\/blood-2013-12-545087","article-title":"HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy","volume":"123","author":"Fajgenbaum","year":"2014","journal-title":"Blood"},{"key":"2026041500574313500_ref11","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/ajh.25495","article-title":"POEMS syndrome: 2019 update on diagnosis, risk-stratification, and management","volume":"94","author":"Dispenzieri","year":"2019","journal-title":"Am J Hematol"},{"key":"2026041500574313500_ref12","doi-asserted-by":"crossref","first-page":"7547","DOI":"10.1073\/pnas.86.19.7547","article-title":"IgG1 plasmacytosis in interleukin 6 transgenic mice","volume":"86","author":"Suematsu","year":"1989","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026041500574313500_ref13","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1006\/cyto.2002.2012","article-title":"Anti-interleukin 6 (IL-6) receptor antibody suppresses Castleman\u2019s disease like symptoms emerged in IL-6 transgenic mice","volume":"20","author":"Katsume","year":"2002","journal-title":"Cytokine"},{"key":"2026041500574313500_ref14","doi-asserted-by":"crossref","first-page":"i21","DOI":"10.1136\/ard.59.suppl_1.i21","article-title":"Anti-interleukin 6 receptor antibody treatment in rheumatic disease","volume":"59","author":"Nishimoto","year":"2000","journal-title":"Ann Rheum Dis"},{"key":"2026041500574313500_ref15","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1080\/14397595.2019.1704983","article-title":"Clinicopathologic characteristics of 342 patients with multicentric Castleman disease in Japan","volume":"30","author":"Murakami","year":"2020","journal-title":"Mod Rheumatol"},{"key":"2026041500574313500_ref16","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1182\/blood-2004-12-4602","article-title":"Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease","volume":"106","author":"Nishimoto","year":"2005","journal-title":"Blood"},{"key":"2026041500574313500_ref17","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/S1470-2045(14)70319-5","article-title":"Siltuximab for multicentric Castleman\u2019s disease: a randomised, double-blind, placebo-controlled trial","volume":"15","author":"Rhee","year":"2014","journal-title":"Lancet Oncol"},{"key":"2026041500574313500_ref18","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.1182\/bloodadvances.2022007112","article-title":"Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease","volume":"6","author":"Rhee","year":"2022","journal-title":"Blood Adv"},{"key":"2026041500574313500_ref19","article-title":"Table-18. List of approved drugs","author":"Pharmaceuticals and Medical Devices Agency","year":"2004   2025"},{"key":"2026041500574313500_ref20","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1080\/14397595.2018.1532383","article-title":"A benefit and the prospects of IL-6 inhibitors in idiopathic multicentric Castleman's disease","volume":"29","author":"Koga","year":"2019","journal-title":"Mod Rheumatol"},{"key":"2026041500574313500_ref21","article-title":"WHO handbook for reporting results of cancer treatment","author":"World Health Organization","year":"1979"},{"key":"2026041500574313500_ref22","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3960\/jslrt.53.69","article-title":"Clinical features and treatment of multicentric Castleman\u2019s disease: a retrospective study of 21 Japanese patients at a single institute","volume":"53","author":"Kawabata","year":"2013","journal-title":"J Clin Exp Hematop"},{"key":"2026041500574313500_ref23","doi-asserted-by":"publisher","DOI":"10.1136\/jcp-2023-209280","article-title":"Diagnostic challenges of the idiopathic plasmacytic lymphadenopathy (IPL) subtype of idiopathic multicentric Castleman disease (iMCD): factors to differentiate from IgG4-related disease","author":"Nishikori","year":"2024","journal-title":"J Clin Pathol"},{"key":"2026041500574313500_ref24","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1002\/ajh.26292","article-title":"Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease","volume":"96","author":"Nishimura","year":"2021","journal-title":"Am J Hematol"},{"key":"2026041500574313500_ref25","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s40271-015-0120-5","article-title":"Patient-reported outcomes for multicentric Castleman\u2019s disease in a randomized, placebo-controlled study of siltuximab","volume":"8","author":"Rhee","year":"2015","journal-title":"Patient"},{"key":"2026041500574313500_ref26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/14397595.2017.1366093","article-title":"Tentative diagnostic criteria and disease severity classification for Castleman disease: a report of the research group on Castleman disease in Japan","volume":"28","author":"Fujimoto","year":"2018","journal-title":"Mod Rheumatol"},{"key":"2026041500574313500_ref27","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1136\/ard.2008.092866","article-title":"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","volume":"68","author":"Nishimoto","year":"2009","journal-title":"Ann Rheum Dis"},{"key":"2026041500574313500_ref28","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3109\/14397595.2013.854069","article-title":"Remission in patients with active rheumatoid arthritis by tocilizumab treatment in routine clinical practice: results from 3 years of prospectively registered data","volume":"24","author":"Nakashima","year":"2014","journal-title":"Mod Rheumatol"},{"key":"2026041500574313500_ref29","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13075-019-1880-4","article-title":"Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis-the ANSWER cohort study","volume":"21","author":"Ebina","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"2026041500574313500_ref30","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1136\/ard.2011.151092","article-title":"Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients","volume":"70","author":"Koike","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"2026041500574313500_ref31","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1136\/annrheumdis-2015-207818","article-title":"Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan","volume":"75","author":"Yokota","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"2026041500574313500_ref32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3899\/jrheum.130466","article-title":"Effectiveness and Safety of Tocilizumab: Postmarketing Surveillance of 7901 Patients with Rheumatoid Arthritis in Japan","volume":"41","author":"Koike","year":"2014","journal-title":"J Rheumatol"}],"container-title":["Modern Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mr\/advance-article-pdf\/doi\/10.1093\/mr\/roaf100\/64825716\/roaf100.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/36\/3\/456\/64825716\/roaf100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mr\/article-pdf\/36\/3\/456\/64825716\/roaf100.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:57:53Z","timestamp":1776229073000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mr\/article\/36\/3\/456\/8294004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,10,21]]},"published-print":{"date-parts":[[2026,4,13]]}},"URL":"https:\/\/doi.org\/10.1093\/mr\/roaf100","relation":{},"ISSN":["1439-7595","1439-7609"],"issn-type":[{"value":"1439-7595","type":"print"},{"value":"1439-7609","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2025,10,21]]}}}