{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:46:46Z","timestamp":1785422806516,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002632","name":"Hallym University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002632","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03sbhge02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Background: Mirikizumab, a first-in-class interleukin-23p19 antagonist, was approved for ulcerative colitis (2023) and Crohn\u2019s disease (2025). The US Food and Drug Administration (FDA) identified a hepatotoxicity signal during pre-approval review, mandating post-marketing surveillance. No independent pharmacovigilance analysis has been published. Aims: To characterise the post-marketing safety profile of mirikizumab using multi-database pharmacovigilance, with a focus on hepatotoxicity and IL-23 inhibitor class comparison. Methods: Disproportionality analysis of the FDA Adverse Event Reporting System (FAERS; Q4 2023\u2013Q4 2025) and Japanese Adverse Drug Event Report database (JADER) was performed using four algorithms (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, empirical Bayesian geometric mean). Signals of disproportionate reporting were defined by concordance of all four methods. Active comparator analysis against risankizumab, guselkumab and ustekinumab, Weibull time-to-onset modelling and hepatotoxicity case characterisation were conducted. Reporting followed READUS-PV guidelines. Results: We identified 564 mirikizumab reports in FAERS and 123 in JADER. Nine signals met all four criteria in FAERS, including spontaneous abortion (Reporting odds ratio (ROR) 10.16, 95% CI 5.16\u201320.02), pulmonary embolism (ROR 5.56, 2.93\u201310.56) and injection site reactions. Hepatotoxicity showed no disproportionate reporting in either FAERS (ROR 1.19, 0.74\u20131.92; n = 17) or JADER (ROR 0.24, 0.05\u20131.19; n = 1). Comparator analysis identified cytomegalovirus infection and interstitial lung disease as mirikizumab-specific versus the IL-23 class. Weibull analysis (\u03b2 = 0.65) indicated early-onset adverse event clustering. Discussion: This first multi-database pharmacovigilance study of mirikizumab did not confirm the FDA-flagged hepatotoxicity signal. Potential signals warranting further investigation include thromboembolic events and pulmonary toxicity.<\/jats:p>","DOI":"10.3390\/bioengineering13070789","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:17:51Z","timestamp":1783606671000},"page":"789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Post-Marketing Safety Profile of Mirikizumab: A Multi-Database Pharmacovigilance Study Using FAERS and JADER with IL-23 Inhibitor Class Comparison"],"prefix":"10.3390","volume":"13","author":[{"given":"Jeong-Gyu","family":"Choi","sequence":"first","affiliation":[{"name":"Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3996-3472","authenticated-orcid":false,"given":"Eun Jeong","family":"Gong","sequence":"additional","affiliation":[{"name":"Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24253, Republic of Korea"},{"name":"Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4908-5431","authenticated-orcid":false,"given":"Chang Seok","family":"Bang","sequence":"additional","affiliation":[{"name":"Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24253, Republic of Korea"},{"name":"Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24253, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Hallym University College of Medicine, Chuncheon 24253, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nri3707","article-title":"The IL-23\u2013IL-17 immune axis: From mechanisms to therapeutic testing","volume":"14","author":"Gaffen","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41575-018-0084-8","article-title":"IL-12, IL-23 and IL-17 in IBD: Immunobiology and therapeutic targeting","volume":"16","author":"Moschen","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1126\/science.1135245","article-title":"A genome-wide association study identifies IL23R as an inflammatory bowel disease gene","volume":"314","author":"Duerr","year":"2006","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nm.3895","article-title":"IL-12 and IL-23 cytokines: From discovery to targeted therapies for immune-mediated inflammatory diseases","volume":"21","author":"Teng","year":"2015","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1053\/j.gastro.2024.05.036","article-title":"Targeting the Interleukin 23 Pathway in Inflammatory Bowel Disease","volume":"168","author":"Bourgonje","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1056\/NEJMoa2207940","article-title":"Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis","volume":"388","author":"Dubinsky","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1007\/s40265-023-01909-1","article-title":"Mirikizumab: First Approval","volume":"83","author":"Keam","year":"2023","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1016\/S0140-6736(24)01762-8","article-title":"Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn\u2019s disease: A phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study","volume":"404","author":"Ferrante","year":"2024","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1053\/j.gastro.2024.10.001","article-title":"AGA Living Clinical Practice Guideline on Pharmacological Management of Moderate-to-Severe Ulcerative Colitis","volume":"167","author":"Singh","year":"2024","journal-title":"Gastroenterology"},{"key":"ref_10","unstructured":"US Food and Drug Administration. Center for Drug Evaluation and Research (2026, March 15). BLA 761279 Other Reviews (ARIA, DILI Consultation), Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2023\/761279Orig1s000Approv.pdf."},{"key":"ref_11","unstructured":"US Food and Drug Administration (2026, March 15). OMVOH (Mirikizumab-Mrkz) Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/761279s003lbl.pdf."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shu, Y., Chen, J., Ding, Y., and Zhang, Q. (2023). Adverse events with risankizumab in the real world: Postmarketing pharmacovigilance assessment of the FDA adverse event reporting system. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1169735"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1111\/bcp.15581","article-title":"Potential cerebrovascular accident signal for risankizumab: A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS)","volume":"89","author":"Woods","year":"2023","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.3390\/pharmaceutics15071933","article-title":"Pharmacovigilance of Risankizumab in the Treatment of Psoriasis and Arthritic Psoriasis: Real-World Data from EudraVigilance Database","volume":"15","author":"Calapai","year":"2023","journal-title":"Pharmaceutics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1080\/14740338.2023.2223956","article-title":"Adverse events of guselkumab in the real world: Emerging signals to target preventive strategies from the FDA adverse event reporting system","volume":"22","author":"Xiang","year":"2023","journal-title":"Expert. Opin. Drug Saf."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, J., Geng, X., Zhang, X., Xiao, Y., and Wang, W. (2022). Hepatitis B Virus Reactivation and Mycobacterial Infections Associated With Ustekinumab: A Retrospective Study of an International Pharmacovigilance Database. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.921084"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Guo, C., and Zhao, S. (2025). Adverse events associated with ustekinumab in Crohn\u2019s disease treatment: An analysis based on the FAERS database. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1657247"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s40001-025-03676-z","article-title":"Safety assessment of ustekinumab in inflammatory bowel disease: A real-world analysis based on the FDA adverse event reporting system (FAERS)","volume":"31","author":"Xu","year":"2025","journal-title":"Eur. J. Med. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"796","DOI":"10.7150\/ijms.6048","article-title":"Data mining of the public version of the FDA Adverse Event Reporting System","volume":"10","author":"Sakaeda","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/pds.4944","article-title":"Quality evaluation of the Japanese Adverse Drug Event Report database (JADER)","volume":"29","author":"Tsuchiya","year":"2020","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fujiwara, M., Kawasaki, Y., and Yamada, H. (2016). A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER) Database and Association Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154425"},{"key":"ref_22","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":"Bate","year":"2002","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_23","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":"Evans","year":"2001","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_24","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":"Bate","year":"1998","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/00031305.1999.10474456","article-title":"Bayesian Data Mining in Large Frequency Tables, with an Application to FDA Spontaneous Reporting System","volume":"53","author":"Dumouchel","year":"1999","journal-title":"Am. Stat."},{"key":"ref_26","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":"Szarfman","year":"2002","journal-title":"Drug Saf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"617","DOI":"10.2165\/00002018-200730070-00009","article-title":"Standardised MedDRA queries: Their role in signal detection","volume":"30","author":"Mozzicato","year":"2007","journal-title":"Drug Saf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s40264-013-0061-7","article-title":"Illustration of the Weibull shape parameter signal detection tool using electronic healthcare record data","volume":"36","author":"Sauzet","year":"2013","journal-title":"Drug Saf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"599","DOI":"10.2165\/11599740-000000000-00000","article-title":"A signal detection method to detect adverse drug reactions using a parametric time-to-event model in simulated cohort data","volume":"35","author":"Cornelius","year":"2012","journal-title":"Drug Saf."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s40264-024-01421-9","article-title":"The Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Development and Statement","volume":"47","author":"Fusaroli","year":"2024","journal-title":"Drug Saf."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s40264-024-01423-7","article-title":"The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration","volume":"47","author":"Fusaroli","year":"2024","journal-title":"Drug Saf."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jentzer, A., Veyrard, P., Roblin, X., Saint-Sardos, P., Rochereau, N., Paul, S., Bourlet, T., Pozzetto, B., and Pillet, S. (2020). Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC). Microorganisms, 8.","DOI":"10.3390\/microorganisms8071078"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shi, W., Zhao, Z., Zhai, Y., Ye, X., and Xu, F. (2025). Adverse events associated with IL-23 and IL-12\/23 inhibitors in the clinical management of psoriasis: A comprehensive pharmacovigilance analysis. BMC Pharmacol. Toxicol., 26.","DOI":"10.1186\/s40360-025-00837-y"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1053\/j.gastro.2020.11.038","article-title":"Pregnancy and Neonatal Outcomes After Fetal Exposure to Biologics and Thiopurines Among Women With Inflammatory Bowel Disease","volume":"160","author":"Mahadevan","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"468","DOI":"10.14309\/ajg.0000000000002553","article-title":"Maternal and Neonatal Outcomes in Vedolizumab- and Ustekinumab-Exposed Pregnancies: Results From the PIANO Registry","volume":"119","author":"Chugh","year":"2024","journal-title":"Am. J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1053\/j.gastro.2014.01.042","article-title":"Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology","volume":"146","author":"Nguyen","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jaad.2020.08.026","article-title":"The risk of respiratory tract infections and interstitial lung disease with interleukin 12\/23 and interleukin 23 antagonists in patients with autoimmune diseases: A systematic review and meta-analysis","volume":"84","author":"Akiyama","year":"2021","journal-title":"J. Am. Acad. Dermatol."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/7\/789\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:17:48Z","timestamp":1783743468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/7\/789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["bioengineering13070789"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13070789","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]}}}