{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:13:02Z","timestamp":1788541982429,"version":"build-2803163510"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Obinutuzumab is the first glycosylated type II anti-CD20 monoclonal antibody for the treatment of lymphocytic leukemia and follicular lymphoma. This research aimed to identify significant and unexpected adverse events (AEs) associated with obinutuzumab by utilizing data from the US Food and Drug Administration\u2019s Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases, with the intention of providing a reference for the safe and rational clinical use of the drug.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Research design and methods<\/jats:title>\n<jats:p>The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric average (EBGM) were employed to analyze the AEs of obinutuzumab using the registration data from the FAERS and JADER databases spanning from 2013 to 2025.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The study screened 7,868 and 1,584 AE reports related to obinutuzumab from the FAERS and JADER databases, respectively. These AEs involved 198 and 39 risk signals, respectively, and were associated with 16 and 8 system organ classes. In the analysis of the top 30 preferred terms, 19 and 15 risk signals in the FAERS and JADER databases, respectively, were not documented in the drug instruction. Moreover, when obinutuzumab is used for tumor indications, the frequency and signal strength of AEs related to infection and infusion-related reaction (IRR) are higher than those when it is used for non-tumor indications.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The results of signal mining indicate that more attention should be paid to the risks of obinutuzumab-related AEs. Strengthening clinical medication monitoring is necessary to mitigate the impact of AEs on patients\u2019 prognosis and quality of life.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0334317","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:31:11Z","timestamp":1760117471000},"page":"e0334317","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Safety assessment of obinutuzumab: Real-world adverse event analysis based on the FAERS and JADER databases from 2013 to 2025"],"prefix":"10.1371","volume":"20","author":[{"given":"Xiangpeng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Leng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-5167","authenticated-orcid":true,"given":"Zhanqi","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"issue":"1","key":"pone.0334317.ref001","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/bjh.15232","article-title":"A tale of two antibodies: obinutuzumab versus rituximab","volume":"182","author":"CL Freeman","year":"2018","journal-title":"Br J Haematol"},{"issue":"6","key":"pone.0334317.ref002","doi-asserted-by":"crossref","first-page":"3762","DOI":"10.4049\/jimmunol.1000303","article-title":"Mechanism of action of type II, glycoengineered, anti-CD20 monoclonal antibody GA101 in B-chronic lymphocytic leukemia whole blood assays in comparison with rituximab and alemtuzumab","volume":"186","author":"L Bologna","year":"2011","journal-title":"J Immunol"},{"issue":"22","key":"pone.0334317.ref003","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1182\/blood-2009-06-225979","article-title":"Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity","volume":"115","author":"E M\u00f6ssner","year":"2010","journal-title":"Blood"},{"issue":"4","key":"pone.0334317.ref004","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000381524","article-title":"Obinutuzumab (GA101) for the treatment of chronic lymphocytic leukemia and other B-cell non-hodgkin\u2019s lymphomas: a glycoengineered type II CD20 antibody","volume":"38","author":"V Goede","year":"2015","journal-title":"Oncol Res Treat"},{"issue":"10","key":"pone.0334317.ref005","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1080\/13696998.2020.1791890","article-title":"Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients","volume":"23","author":"S Ohno","year":"2020","journal-title":"J Med Econ"},{"issue":"14","key":"pone.0334317.ref006","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1056\/NEJMoa1614598","article-title":"Obinutuzumab for the first-line treatment of follicular lymphoma","volume":"377","author":"R Marcus","year":"2017","journal-title":"N Engl J Med"},{"issue":"2","key":"pone.0334317.ref007","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/hon.2828","article-title":"Obinutuzumab-related adverse events: a systematic review and meta-analysis","volume":"39","author":"I Amitai","year":"2021","journal-title":"Hematol Oncol"},{"issue":"1","key":"pone.0334317.ref008","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1038\/s41598-021-82841-w","article-title":"Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis","volume":"11","author":"C Luo","year":"2021","journal-title":"Sci Rep"},{"issue":"12","key":"pone.0334317.ref009","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1007\/s00277-020-04021-6","article-title":"Health-related quality of life in the phase III GALLIUM study of obinutuzumab- or rituximab-based chemotherapy in patients with previously untreated advanced follicular lymphoma","volume":"99","author":"A Davies","year":"2020","journal-title":"Ann Hematol"},{"issue":"7","key":"pone.0334317.ref010","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/leu.2015.14","article-title":"Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study","volume":"29","author":"V Goede","year":"2015","journal-title":"Leukemia"},{"issue":"31","key":"pone.0334317.ref011","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1200\/JCO.2017.73.3402","article-title":"Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma","volume":"35","author":"U Vitolo","year":"2017","journal-title":"J Clin Oncol"},{"issue":"24","key":"pone.0334317.ref012","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1182\/blood-2015-09-670802","article-title":"Cytokine release in patients with CLL treated with obinutuzumab and possible relationship with infusion-related reactions","volume":"126","author":"CL Freeman","year":"2015","journal-title":"Blood"},{"key":"pone.0334317.ref013","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.2147\/DDDT.S81998","article-title":"Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases","volume":"9","author":"K Nomura","year":"2015","journal-title":"Drug Des Devel Ther"},{"issue":"12","key":"pone.0334317.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0260980","article-title":"Analysis of anticholinergic adverse effects using two large databases: the US food and drug administration adverse event reporting system database and the Japanese adverse drug event report database","volume":"16","author":"J Nagai","year":"2021","journal-title":"PLoS One"},{"issue":"6","key":"pone.0334317.ref015","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/pds.677","article-title":"Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports","volume":"10","author":"SJ Evans","year":"2001","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"1","key":"pone.0334317.ref016","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/pds.668","article-title":"A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions","volume":"11","author":"EP van Puijenbroek","year":"2002","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"4","key":"pone.0334317.ref017","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s002280050466","article-title":"A Bayesian neural network method for adverse drug reaction signal generation","volume":"54","author":"A Bate","year":"1998","journal-title":"Eur J Clin Pharmacol"},{"issue":"6","key":"pone.0334317.ref018","doi-asserted-by":"crossref","first-page":"381","DOI":"10.2165\/00002018-200225060-00001","article-title":"Use of screening algorithms and computer systems to efficiently signal higher-than-expected combinations of drugs and events in the US FDA\u2019s spontaneous reports database","volume":"25","author":"A Szarfman","year":"2002","journal-title":"Drug Saf"},{"issue":"4","key":"pone.0334317.ref019","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s00262-019-02304-0","article-title":"Mutations resulting in the formation of hyperactive complement convertases support cytocidal effect of anti-CD20 immunotherapeutics","volume":"68","author":"A Felberg","year":"2019","journal-title":"Cancer Immunol Immunother"},{"issue":"6","key":"pone.0334317.ref020","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1158\/1535-7163.MCT-20-0864","article-title":"Obinutuzumab in combination with chemotherapy enhances direct cell death in CD20-positive obinutuzumab-resistant non-hodgkin lymphoma cells","volume":"20","author":"T Fujimura","year":"2021","journal-title":"Mol Cancer Ther"},{"issue":"3","key":"pone.0334317.ref021","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"F Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"pone.0334317.ref022","first-page":"5","article-title":"Epidemiology of Non-Hodgkin\u2019s Lymphoma","volume":"9","author":"KC Thandra","year":"2021","journal-title":"Med Sci (Basel)"},{"issue":"1","key":"pone.0334317.ref023","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00277-014-2120-2","article-title":"Invasive fungal infections after obinutuzumab monotherapy for refractory chronic lymphocytic leukemia","volume":"94","author":"E Tse","year":"2015","journal-title":"Ann Hematol"},{"issue":"10","key":"pone.0334317.ref024","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1158\/1535-7163.MCT-12-1182","article-title":"Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models","volume":"12","author":"S Herter","year":"2013","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"pone.0334317.ref025","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s12985-024-02484-x","article-title":"Outcomes of COVID-19 in patients with obinutuzumab compared with patients with rituximab: a retrospective cohort study","volume":"21","author":"W Shu","year":"2024","journal-title":"Virol J"},{"issue":"2","key":"pone.0334317.ref026","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.idc.2020.02.009","article-title":"Hepatitis B Virus Reactivation Potentiated by Biologics","volume":"34","author":"E Ogawa","year":"2020","journal-title":"Infect Dis Clin North Am"},{"issue":"4","key":"pone.0334317.ref027","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jbspin.2011.11.002","article-title":"Progressive multifocal leukoencephalopathy in autoimmune diseases","volume":"79","author":"E Palazzo","year":"2012","journal-title":"Joint Bone Spine"},{"issue":"7","key":"pone.0334317.ref028","doi-asserted-by":"crossref","DOI":"10.1016\/j.clml.2021.02.016","article-title":"Progressive multifocal leukoencephalopathy following treatment with obinutuzumab in a patient with non-hodgkin follicular lymphoma: a case report","volume":"21","author":"S Diavati","year":"2021","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"6","key":"pone.0334317.ref029","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/ana.26198","article-title":"Advances in treatment of progressive multifocal leukoencephalopathy","volume":"90","author":"R Bernard-Valnet","year":"2021","journal-title":"Ann Neurol"},{"key":"pone.0334317.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-0716-1111-1_1","article-title":"Overview of human cytomegalovirus pathogenesis","volume":"2244","author":"HL Fulkerson","year":"2021","journal-title":"Methods Mol Biol"},{"issue":"4","key":"pone.0334317.ref031","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.DMIH2-0022-2015","article-title":"Cytomegalovirus","volume":"4","author":"MV Dioverti","year":"2016","journal-title":"Microbiol Spectr"},{"issue":"2","key":"pone.0334317.ref032","doi-asserted-by":"crossref","first-page":"923","DOI":"10.21873\/invivo.13520","article-title":"Cytomegalovirus occurrence and time-to-onset analysis under bendamustine with anti-CD20 antibodies using the JADER database","volume":"38","author":"K Ito","year":"2024","journal-title":"In Vivo"},{"issue":"4","key":"pone.0334317.ref033","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/ajh.20028","article-title":"Case report of rituximab-induced thrombocytopenia","volume":"75","author":"C Shah","year":"2004","journal-title":"Am J Hematol"},{"issue":"8","key":"pone.0334317.ref034","doi-asserted-by":"crossref","DOI":"10.1097\/HS9.0000000000000751","article-title":"Successful use of intravenous immunoglobulins in an obinutuzumab-related acute thrombocytopenia","volume":"6","author":"TR Haage","year":"2022","journal-title":"Hemasphere"},{"issue":"6","key":"pone.0334317.ref035","doi-asserted-by":"crossref","DOI":"10.1038\/bcj.2016.42","article-title":"Obinutuzumab-induced coagulopathy in chronic lymphocytic leukaemia with trisomy 12","volume":"6","author":"HS Walter","year":"2016","journal-title":"Blood Cancer J"},{"issue":"1","key":"pone.0334317.ref036","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1182\/hematology.2020000120","article-title":"Preventing and monitoring for tumor lysis syndrome and other toxicities of venetoclax during treatment of chronic lymphocytic leukemia","volume":"2020","author":"K Fischer","year":"2020","journal-title":"Hematology Am Soc Hematol Educ Program"},{"issue":"1","key":"pone.0334317.ref037","first-page":"000516","article-title":"Tumour lysis syndrome and partial remission occurring after administration of a test dose of obinutuzumab","volume":"4","author":"M Mustafa","year":"2017","journal-title":"Eur J Case Rep Intern Med"},{"issue":"5","key":"pone.0334317.ref038","doi-asserted-by":"crossref","DOI":"10.1053\/j.ackd.2021.09.007","article-title":"Tumor lysis syndrome","volume":"28","author":"T Barbar","year":"2021","journal-title":"Adv Chronic Kidney Dis"},{"issue":"11","key":"pone.0334317.ref039","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.3324\/haematol.2017.186387","article-title":"Safety of obinutuzumab alone or combined with chemotherapy for previously untreated or relapsed\/refractory chronic lymphocytic leukemia in the phase IIIb GREEN study","volume":"103","author":"V Leblond","year":"2018","journal-title":"Haematologica"},{"issue":"5","key":"pone.0334317.ref040","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1177\/0192623317723539","article-title":"Hypersensitivity reactions to obinutuzumab in cynomolgus monkeys and relevance to humans","volume":"45","author":"E Husar","year":"2017","journal-title":"Toxicol Pathol"},{"issue":"2","key":"pone.0334317.ref041","doi-asserted-by":"crossref","DOI":"10.1188\/16.CJON.E41-E48","article-title":"Managing infusion-related reactions for patients with chronic lymphocytic leukemia receiving obinutuzumab","volume":"20","author":"K Dawson","year":"2016","journal-title":"Clin J Oncol Nurs"},{"issue":"7","key":"pone.0334317.ref042","doi-asserted-by":"crossref","first-page":"437","DOI":"10.6004\/jadpro.2024.15.7.2","article-title":"Obinutuzumab infusion-related reactions: multicenter retrospective evaluation of incidence, severity, and risk factors","volume":"15","author":"EH Zacholski","year":"2024","journal-title":"J Adv Pract Oncol"},{"issue":"5","key":"pone.0334317.ref043","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1002\/art.41608","article-title":"The type II Anti-CD20 antibody obinutuzumab (GA101) is more effective than rituximab at depleting B cells and treating disease in a murine lupus model","volume":"73","author":"AD Marinov","year":"2021","journal-title":"Arthritis Rheumatol"},{"issue":"12","key":"pone.0334317.ref044","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1093\/rheumatology\/keac150","article-title":"Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab","volume":"61","author":"J Arnold","year":"2022","journal-title":"Rheumatology (Oxford)"},{"issue":"1","key":"pone.0334317.ref045","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1136\/annrheumdis-2021-220920","article-title":"B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial","volume":"81","author":"RA Furie","year":"2022","journal-title":"Ann Rheum Dis"},{"issue":"15","key":"pone.0334317.ref046","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1056\/NEJMoa2410965","article-title":"Efficacy and safety of obinutuzumab in active lupus nephritis","volume":"392","author":"RA Furie","year":"2025","journal-title":"N Engl J Med"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0334317","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:31:19Z","timestamp":1760117479000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0334317"}},"subtitle":[],"editor":[{"given":"Nestor","family":"Oliva Damaso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0334317","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]}}}