{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:50:53Z","timestamp":1788871853545,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Anti-tumour necrosis factor (TNF) agents are effective in Crohn\u2019s disease (CD), but some patients lose responsiveness and require alternative biologic therapy. Until recently, ustekinumab and vedolizumab were the only other biological agents approved for use in CD. There are no randomised trials which compare the efficacy of these two agents in patients with anti-TNF refractory disease, but several retrospective cohort studies have compared their effectiveness in this setting. Aim: To review the effectiveness of ustekinumab and vedolizumab in anti-TNF refractory patients with CD. Methods: We included studies that compared the effectiveness of ustekinumab and vedolizumab in treating patients with anti-TNF refractory CD. We recorded the sample size, primary and secondary outcome measures and whether the studies employed adjustments for appropriate confounders. Results: Fourteen studies were included with a total sample size of 5651, of whom 2181 (38.6%) were treated with vedolizumab and the rest were treated with ustekinumab (61.4%). Of the fourteen studies included, eight found ustekinumab to be more effective in achieving clinical remission\/steroid-free remission in the induction phase or during maintenance therapy (at least 1-year post-treatment) or that treatment persistence rates with ustekinumab were higher than with vedolizumab. Only one study reported vedolizumab to be superior during the maintenance phase in terms of clinical remission or treatment persistence rates. Biochemical outcomes were reported in five studies, two of which showed superiority for ustekinumab at 14 weeks and the other at 52 weeks. Only two studies reported endoscopic and\/or radiologic outcomes; of these, one study showed ustekinumab to be significantly better at achieving endoscopic and radiologic responses. Adverse outcomes were broadly comparable, barring a single study which reported a lower hospitalisation rate for severe infection with ustekinumab. Conclusions: Most studies found ustekinumab to be more effective or non-inferior to vedolizumab in treating patients with anti-TNF refractory CD. Although many studies adjusted appropriately for confounders, the possibility of residual confounding remains and further data from prospective studies are warranted to confirm these findings. Further studies are required to compare these two therapies to other emerging therapies, such as Janus-kinase inhibitors.<\/jats:p>","DOI":"10.3390\/jcm13082187","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T06:07:46Z","timestamp":1712729266000},"page":"2187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ustekinumab or Vedolizumab after Failure of Anti-TNF Agents in Crohn\u2019s Disease: A Review of Comparative Effectiveness Studies"],"prefix":"10.3390","volume":"13","author":[{"given":"Mohmmed","family":"Sharip","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilanga","family":"Nishad","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lushen","family":"Pillay","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilkantsingh","family":"Goordyal","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Goerge","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreedhar","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Cambridge University Hospital NHS Foundation Trust, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/ecco-jcc\/jjw092","article-title":"An Overview of the Mechanism of Action of the Monoclonal Antibody Vedolizumab","volume":"10","author":"Wyant","year":"2016","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.4161\/mabs.3.6.17815","article-title":"Discovery and mechanism of ustekinumab: A human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders","volume":"3","author":"Benson","year":"2011","journal-title":"MAbs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.autrev.2013.06.002","article-title":"Optimizing anti-TNF treatments in inflammatory bowel disease","volume":"13","author":"Kopylov","year":"2014","journal-title":"Autoimmun. Rev"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1016\/j.cgh.2008.06.007","article-title":"Treatment of active Crohn\u2019s disease with MLN0002, a humanized antibody to the \u03b14\u03b27 integrin","volume":"6","author":"Feagan","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1056\/NEJMoa1203572","article-title":"Ustekinumab induction and maintenance therapy in refractory Crohn\u2019s disease","volume":"367","author":"Sandborn","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"i117","DOI":"10.1093\/ecco-jcc\/jjab232.113","article-title":"Comparative effectiveness of vedolizumab and ustekinumab in Crohn\u2019s Disease patients who failed anti-TNF treatment: Interrogating 1019 patients from the UK IBD BioResource","volume":"16","author":"Desoki","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102337","DOI":"10.1016\/j.eclinm.2023.102337","article-title":"Comparative effectiveness of ustekinumab vs. vedolizumab for anti-TNF-na\u00efve or anti-TNF-exposed Crohn\u2019s disease: A multicenter cohort study","volume":"66","author":"Yang","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1111\/apt.16057","article-title":"Comparative effectiveness of ustekinumab or vedolizumab after one year in 130 patients with anti-TNF-refractory Crohn\u2019s disease","volume":"52","author":"Townsend","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1243080","DOI":"10.3389\/fphar.2023.1243080","article-title":"Effectiveness of vedolizumab and ustekinumab as second biologic agent in achieving target outcomes in tumor necrosis factor antagonists experienced patients with inflammatory bowel disease (enroll-ex study)","volume":"14","author":"Alrashed","year":"2023","journal-title":"Front. Pharmacol"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hyun, H.K., Zhang, H.S., Yu, J., Kang, E.A., Park, J., Park, S.J., Park, J.J., Kim, T.I., Kim, W.H., and Cheon, J.H. (2022). Comparative effectiveness of second-line biological therapies for ulcerative colitis and Crohn\u2019s disease in patients with prior failure of anti-tumour necrosis factor treatment. BMC Gastroenterol., 22.","DOI":"10.1186\/s12876-022-02225-w"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rayer, C., Nachury, M., Bourreille, A., Roblin, X., Peyrin-Biroulet, L., Viennot, S., Flamant, M., Laharie, D., Caron, B., and Dewitte, M. (2022). Efficacy of ustekinumab, vedolizumab, or a second anti-TNF agent after the failure of a first anti-TNF agent in patients with Crohn\u2019s disease: A multicentre retrospective study. BMC Gastroenterol., 22.","DOI":"10.1186\/s12876-022-02583-5"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1111\/apt.15706","article-title":"The effectiveness of either ustekinumab or vedolizumab in 239 patients with Crohn\u2019s disease refractory to anti-tumour necrosis factor","volume":"51","author":"Alric","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/apt.15745","article-title":"Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn\u2019s disease patients with prior failure to anti-TNF treatment","volume":"52","author":"Biemans","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1111\/apt.16377","article-title":"Comparison of short-and long-term effectiveness between ustekinumab and vedolizumab in patients with Crohn\u2019s disease refractory to anti-tumour necrosis factor therapy","volume":"53","author":"Manlay","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/apt.16742","article-title":"A propensity score-matched, real-world comparison of ustekinumab vs vedolizumab as a second-line treatment for Crohn\u2019s disease. The cross Pennine study II","volume":"55","author":"Lenti","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.14309\/ajg.0000000000001773","article-title":"An objective comparison of vedolizumab and ustekinumab effectiveness in Crohn\u2019s disease patients\u2019 failure to TNF-alpha inhibitors Off","volume":"117","author":"Onali","year":"2022","journal-title":"J. Am. Coll. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"674","DOI":"10.14309\/ajg.0000000000002068","article-title":"Real-world evidence comparing vedolizumab and ustekinumab in antitumor necrosis factor-experienced patients with Crohn\u2019s disease","volume":"118","author":"Kappelman","year":"2023","journal-title":"Off. J. Am. Coll. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/ecco-jcc\/jjad124","article-title":"Comparative Study of the Effectiveness of Vedolizumab versus Ustekinumab After Anti-TNF Failure in Crohn\u2019s Disease (Versus-CD): Data from the ENEIDA Registry","volume":"18","author":"Rivero","year":"2024","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kapizioni, C., Desoki, R., Lam, D., Balendran, K., Al-Sulais, E., Subramanian, S., Rimmer, J.E., De La Revilla Negro, J., Pavey, H., and Pele, L. (2023). Biologic therapy for inflammatory bowel disease: Real-world comparative effectiveness and impact of drug sequencing in 13222 patients within the UK IBD BioResource. J. Crohn\u2019s Colitis, jjad203.","DOI":"10.1093\/ecco-jcc\/jjad203"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17562848221144349","DOI":"10.1177\/17562848221144349","article-title":"Ustekinumab is associated with superior treatment persistence but not with higher remission rates versus vedolizumab in patients with refractory Crohn\u2019s disease: Results from a multicentre cohort study","volume":"15","author":"Bacsur","year":"2022","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/apt.16802","article-title":"Systematic review with meta-analysis: Loss of response and requirement of ustekinumab dose escalation in inflammatory bowel diseases","volume":"55","author":"Yang","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_22","first-page":"361","article-title":"The outcomes of patients treated with 2nd and 3rd line biological in perianal Crohn\u2019s disease (PCD)\u2014A multicentre propensity score matched study","volume":"11","author":"Shani","year":"2023","journal-title":"UEG J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.14309\/ajg.0000000000000810","article-title":"Ustekinumab for perianal Crohn\u2019s disease: The BioLAP multicenter study from the GETAID","volume":"115","author":"Kirchgesner","year":"2020","journal-title":"Off. J. Am. Coll. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.cgh.2018.06.026","article-title":"Loss of response to vedolizumab and ability of dose intensification to restore response in patients with Crohn\u2019s disease or ulcerative colitis: A systematic review and meta-analysis","volume":"17","author":"Danese","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1053\/j.gastro.2014.05.008","article-title":"Effects of vedolizumab induction therapy for patients with Crohn\u2019s disease in whom tumor necrosis factor antagonist treatment failed","volume":"147","author":"Sands","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/apt.15609","article-title":"A clinical decision support tool may help to optimise vedolizumab therapy in Crohn\u2019s disease","volume":"51","author":"Dulai","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/ecco-jcc\/jjy019","article-title":"Efficacy of vedolizumab in fistulising Crohn\u2019s disease: Exploratory analyses of data from GEMINI 2","volume":"12","author":"Feagan","year":"2018","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S185","DOI":"10.1016\/S0016-5085(17)30930-7","article-title":"Fistula healing in pivotal studies of ustekinumab in Crohn\u2019s disease","volume":"152","author":"Sands","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/apt.15665","article-title":"Vedolizumab for perianal Crohn\u2019s disease: A multicentre cohort study in 151 patients","volume":"51","author":"Bourrier","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1111\/apt.16073","article-title":"Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study","volume":"52","author":"Asscher","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1053\/j.gastro.2020.02.032","article-title":"Pretreatment Frailty Is Independently Associated with Increased Risk of Infections after Immunosuppression in Patients with Inflammatory Bowel Diseases","volume":"158","author":"Kochar","year":"2020","journal-title":"Gastroenterology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/8\/2187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:25:37Z","timestamp":1760106337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/8\/2187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,10]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["jcm13082187"],"URL":"https:\/\/doi.org\/10.3390\/jcm13082187","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,10]]}}}