{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:00:54Z","timestamp":1790150454630,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To compare risks of malignancy, opportunistic infections, and venous thromboembolism between the targeted synthetic disease\u2010modifying antirheumatic drugs (tsDMARDs) and biologic DMARDs (bDMARDs) at the 2nd and 3rd lines of therapy (LOT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a cohort study using the National Database of Health Insurance Claims (2013\u20132021). Patients with rheumatoid arthritis (RA) initiating tsDMARDs or bDMARDs after conventional synthetic DMARDs (csDMARDs) were identified at the 2nd LOT or 3rd LOT. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox models weighted by inverse probability of treatment weighting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 498\u2009813 csDMARD initiators, 66\u2009638 and 4177 initiated bDMARDs and tsDMARDs at 2nd LOT; 14\u2009085 and 1757 initiated bDMARDs and tsDMARDs at 3rd LOT. For malignancy, HRs (95% CIs) for tsDMARDs versus bDMARDs were 0.92 (0.60\u20131.43) at 2nd LOT and 0.94 (0.53\u20131.65) at 3rd LOT. HRs (95% CIs) for pneumocystis pneumonia (PCP) and deep vein thrombosis (DVT) were as follows: PCP, 0.98 (0.75\u20131.29) at 2nd LOT and 1.12 (0.81\u20131.54) at 3rd LOT; DVT, 1.13 (0.64\u20131.99) at 2nd LOT and 0.96 (0.52\u20131.78) at 3rd LOT. In contrast, herpes zoster (HZ) risk was consistently higher with tsDMARDs (2nd LOT: HR, 2.61 [95% CI, 2.24\u20133.05]; 3rd LOT: HR, 2.90 [95% CI, 2.38\u20133.53]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In the nationwide Japanese cohort, tsDMARDs did not show increased malignancy risk compared to bDMARDs, and PCP risk had no clear difference at 2nd and 3rd LOTs, whereas the risk of HZ was higher with tsDMARDs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.70838","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T07:41:31Z","timestamp":1787902891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Safety Analysis of Targeted Synthetic and Biologic Disease\u2010Modifying Antirheumatic Drugs Among Patients With Rheumatoid Arthritis: A Nationwide Cohort Study in Japan"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1319-3158","authenticated-orcid":false,"given":"Shiori","family":"Nishimura","sequence":"first","affiliation":[{"name":"Department of Healthcare Quality Assessment The University of Tokyo Graduate School of Medicine  Bunkyo Tokyo Japan"},{"name":"Department of Health Data Science Graduate School of Data Science, Yokohama City University  Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2932-6375","authenticated-orcid":false,"given":"Toshitaka","family":"Hirano","sequence":"additional","affiliation":[{"name":"Pfizer Japan Inc.  Shibuya Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soko","family":"Setoguchi","sequence":"additional","affiliation":[{"name":"Department of Medicine Rutgers Robert Wood Johnson Medical School  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology and Health Economics, School of Public Health The University of Tokyo  Bunkyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Data Science, School of Data Science Yokohama City University  Yokohama Kanagawa Japan"},{"name":"Department of Biostatistics, School of Public Health Graduate School of Medicine, The University of Tokyo  Bunkyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Japanese Red Cross Fukuoka Hospital  Fukuoka Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Molecular Targeted Therapeutics University of Occupational and Environmental Health  Kitakyushu Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8858-9435","authenticated-orcid":false,"given":"Kunihiro","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Kitasato University School of Medicine  Sagamihara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6418-0547","authenticated-orcid":false,"given":"Yoichi","family":"Ii","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan G.K.  Shibuya Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Hiro","sequence":"additional","affiliation":[{"name":"Pfizer R&amp;D Japan G.K.  Shibuya Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-1807","authenticated-orcid":false,"given":"Masato","family":"Hoshi","sequence":"additional","affiliation":[{"name":"Pfizer Japan Inc.  Shibuya Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naonobu","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Pfizer Japan Inc (at time of study)  Shibuya Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2009-6831","authenticated-orcid":false,"given":"Yutaka","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health Graduate School of Medicine, The University of Tokyo  Bunkyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9759-6191","authenticated-orcid":false,"given":"Hiraku","family":"Kumamaru","sequence":"additional","affiliation":[{"name":"Department of Healthcare Quality Assessment The University of Tokyo Graduate School of Medicine  Bunkyo Tokyo Japan"},{"name":"Department of Health Data Science Graduate School of Data Science, Yokohama City University  Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/14397595.2013.854059"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2007.08.006"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30134"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010015\u20100728\u20109"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2404"},{"issue":"2","key":"e_1_2_12_7_1","first-page":"217","article-title":"Chronic Inflammation and Cancer","volume":"16","author":"Shacter E.","year":"2002","journal-title":"Oncology (Williston Park, N.Y.)"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.20.2337"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24596"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/mr\/roac017"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard\u20102022\u2010223356"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/mr\/roaf006"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/mr\/road098"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key287"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102016\u2010210457"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen\u20102020\u2010001395"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102019\u2010216761"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42846"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102014\u2010205847"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2022.2014323"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/mr\/roaf017"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/mr\/road063"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109927"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.37737\/ace.24011"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5263"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879\u2010023\u201008466\u20108"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard\u20102022\u2010222543"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard\u20102022\u2010223715"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42250"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11232"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.20064"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102021\u2010220651"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard\u20102022\u2010223762"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010022\u201002871\u20101"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/mr\/roac133"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102017\u2010211796"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab647"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem076"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.144741"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b25\u201000126"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185x.70838","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1756-185x.70838","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185x.70838","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:05:56Z","timestamp":1790147156000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185x.70838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":39,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/1756-185x.70838"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.70838","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"value":"1756-1841","type":"print"},{"value":"1756-185X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"assertion":[{"value":"2026-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70838"}}