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The aim of this study is to investigate the therapeutic effects of targeted therapies in moderate\u2010to\u2010severe UC. The Cochrane Library, Web of Science, PubMed, and Embase were searched from the inception to November 12, 2024. Statistical analyses included multivariate random effects models and Bayesian modeling. Stratified and sensitivity analyses were also performed. Publication bias was assessed using funnel plots. Outcomes such as clinical response\/remission, endoscopic remission, mucosal healing, quality of life, adverse events (AEs), and serious adverse events (SAEs) were used to quantify the relative therapeutic effects. Thirty\u2010three studies (33 reported on the induction phase; 13 reported on the maintenance phase) were identified. In the induction phase, Upadacitinib 45\u2009mg demonstrated the highest efficacy in achieving clinical remission (OR 10.03; 95% CI, 4.83\u201320.80), clinical response (OR 7.96; 95% CI, 3.89\u201316.28), and mucosal healing rate (OR 8.91; 95% CI, 3.36\u201323.62). Cobitolimod 250\u2009mg was the first\u2010ranked treatment (SUCRA, 92.67%) in Endoscopic remission. Vedolizumab 108\u2009mg was the best dosage in reducing Adverse Events (AEs). The optimal dosage for reducing Serious Adverse Events (SAEs) was found to be Tulisokibart 1000\/500\u2009mg. During the maintenance phase, Etrasimod 2\u2009mg\/kg ranked first in clinical remission (OR 9.58; 95% CI, 2.82\u201332.59), and Upadacitinib 45\u2009mg was superior in endoscopic remission. Additionally, the most effective medication for raising quality of life was Guselkumab 200\u2009mg (OR 3.04; 95% CI, 1.70\u20135.40). Consequently, there is a need for further high\u2010quality research to conclusively determine the best therapeutic option.<\/jats:p>","DOI":"10.1002\/prp2.70108","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T07:50:47Z","timestamp":1749109847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparative Efficacy of Different Targeted Therapies in Patients With Moderate\u2010to\u2010Severe Ulcerative Colitis: Systematic Review\/Network Meta\u2010Analysis and Mechanistic Overview"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1289-4426","authenticated-orcid":false,"given":"Youran","family":"Dai","sequence":"first","affiliation":[{"name":"The First Clinical College Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Clinical College Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anorectal Surgery The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingting","family":"Pan","sequence":"additional","affiliation":[{"name":"The Second Clinical College Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Clinical Evaluation and Analysis The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhe","family":"Sun","sequence":"additional","affiliation":[{"name":"The College of Stomatology Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suying","family":"Hu","sequence":"additional","affiliation":[{"name":"The school of Pharmacy Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5176-3719","authenticated-orcid":false,"given":"Qiushuang","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Clinical Evaluation and Analysis The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3311-9821","authenticated-orcid":false,"given":"Fang","family":"Hu","sequence":"additional","affiliation":[{"name":"GCP Clinical Triallnstitution Office The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izx100"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04234.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000152"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00966-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.08.003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0272989X12458724"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102832"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jcag\/gwad032"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2023.07.001"},{"key":"e_1_2_10_11_1","unstructured":"Excellence N.I.f.C \u201cVedolizumab for Treating Moderately to Severely Active Ulcerative Colitis \u201d2015 https:\/\/www.nice.org.uk\/guidance\/ta342."},{"key":"e_1_2_10_12_1","unstructured":"J. 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