{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:56:00Z","timestamp":1761630960255,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"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: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn\u2019s disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156\/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48\/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16\u201322, 87\/156 (55.5%) patients and 27\/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41\/156 (26.2%) and 15\/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89\/103 (86%) patients and 25\/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31\/103 (30%) and 47\/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.<\/jats:p>","DOI":"10.3390\/jcm10132914","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:52:46Z","timestamp":1624963966000},"page":"2914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effectiveness of Third-Class Biologic Treatment in Crohn\u2019s Disease: A Multi-Center Retrospective Cohort Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8962-4263","authenticated-orcid":false,"given":"Ahmad","family":"Albshesh","sequence":"first","affiliation":[{"name":"Sheba Medical Center, Department of Gastroenterology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 52621, Israel"}]},{"given":"Joshua","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Montreal General Hospital, Montreal, QC 1650, Canada"}]},{"given":"Edoardo V.","family":"Savarino","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy"}]},{"given":"Marie","family":"Truyens","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, Ghent University Hospital, 9000 Ghent, Belgium"}]},{"given":"Alessandro","family":"Armuzzi","sequence":"additional","affiliation":[{"name":"IBD Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-3087","authenticated-orcid":false,"given":"Davide G.","family":"Ribaldone","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}]},{"given":"Ariella Bar-Gil","family":"Shitrit","sequence":"additional","affiliation":[{"name":"Shaare Zedek Medical Center, Faculty of Medicine, Digestive Diseases Institute, Hebrew University of Jerusalem, Jerusalem 9372212, Israel"}]},{"given":"Morine","family":"Fibelman","sequence":"additional","affiliation":[{"name":"Tel Aviv Medical Center, Department of Gastroenterology and Liver Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6423906, Israel"}]},{"given":"Pauliina","family":"Molander","sequence":"additional","affiliation":[{"name":"Abdominal Center, Department of Gastroenterology, Helsinki University Hospital, 00101 Helsinki, Finland"}]},{"given":"Claire","family":"Liefferinckx","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Erasme University Hopital, 1070 Brussels, Belgium"}]},{"given":"Stephane","family":"Nancey","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospices Civils de Lyon, University Claude Bernard Lyon, 69495 Lyon, France"},{"name":"INSERM, U1111, CIRI, 69007 Lyon, France"}]},{"given":"Mohamed","family":"Korani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester M8 6RB, UK"},{"name":"Manchester Academic Health Sciences, University of Manchester, Manchester BL97TD, UK"}]},{"given":"Mariann","family":"Rutka","sequence":"additional","affiliation":[{"name":"First Department of Medicine, University of Szeged, H-6720 Szeged, Hungary"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5915-1477","authenticated-orcid":false,"given":"Manuel","family":"Barreiro-de Acosta","sequence":"additional","affiliation":[{"name":"IBD Unit, Gastroenterology Department, University Hospital of Santiago de Compostela, 15706 Santiago, Spain"}]},{"given":"Viktor","family":"Domislovic","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Nutrition, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}]},{"given":"Gerard","family":"Suris","sequence":"additional","affiliation":[{"name":"Digestive System Service, Bellvitge University Hospital, Catalan Institute of Health, 08907 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-383X","authenticated-orcid":false,"given":"Carl","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine and Health, \u00d6rebro University, SE-70182 \u00d6rebro, Sweden"}]},{"given":"Catarina","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Centro Hospitalar S\u00e3o Jo\u00e3o, 4200319 Porto, Portugal"}]},{"given":"Afroditi","family":"Mpitouli","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Venizeleion General Hospital, Heraklion, 71409 Crete, Greece"}]},{"given":"Caroline","family":"di Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Addenbrooke\u2019s Hospital, Cambridge University Hospitals, Cambridge CB2 0QQ, UK"}]},{"given":"Katja","family":"Tepe\u0161","sequence":"additional","affiliation":[{"name":"University Medical Centre Ljubljana, Department of Gastroenterology, Medical Faculty, University of Ljubljana, 1231 Ljubljana, Slovenia"}]},{"given":"Marina","family":"Coletta","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Clinical Gastroenterology, ASST Santi Paolo e Carlo-Ospedale San Polo Universitario Milano Mariabeatrice, 20142 Milan, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0554-5256","authenticated-orcid":false,"given":"Kalliopi","family":"Foteinogiannopoulou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital of Heraklion, 71500 Crete, Greece"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2090-3445","authenticated-orcid":false,"given":"Javier P.","family":"Gisbert","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Hospital Universitario de La Princesa, Instituto de Investigaci\u00f3n Sanitaria Princesa (IIS-IP), Universidad Aut\u00f3noma de Madrid, 28001 Madrid, Spain"}]},{"given":"Hadar","family":"Amir-Barak","sequence":"additional","affiliation":[{"name":"IBD Center, Division of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 49100, Israel"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0323-7030","authenticated-orcid":false,"given":"Mohamed","family":"Attauabi","sequence":"additional","affiliation":[{"name":"Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, 2650 Copenhagen, Denmark"}]},{"given":"Jakob","family":"Seidelin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Herlev University Hospital, 3400 Copenhagen, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6869-0982","authenticated-orcid":false,"given":"Waqqas","family":"Afif","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Montreal General Hospital, Montreal, QC 1650, Canada"}]},{"given":"Carla","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1817-7704","authenticated-orcid":false,"given":"Triana","family":"Lobaton","sequence":"additional","affiliation":[{"name":"IBD Unit, Department of Gastroenterology, Ghent University Hospital, 9000 Ghent, Belgium"}]},{"given":"Daniela","family":"Pugliese","sequence":"additional","affiliation":[{"name":"IBD Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}]},{"given":"Nitsan","family":"Maharshak","sequence":"additional","affiliation":[{"name":"Tel Aviv Medical Center, Department of Gastroenterology and Liver Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6423906, Israel"}]},{"given":"Anneline","family":"Cremer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Erasme University Hopital, 1070 Brussels, Belgium"}]},{"given":"Jimmy K.","family":"Limdi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester M8 6RB, UK"},{"name":"Manchester Academic Health Sciences, University of Manchester, Manchester BL97TD, UK"}]},{"given":"Tam\u00e1s","family":"Moln\u00e1r","sequence":"additional","affiliation":[{"name":"First Department of Medicine, University of Szeged, H-6720 Szeged, Hungary"}]},{"given":"Borja","family":"Otero-Alvarin","sequence":"additional","affiliation":[{"name":"IBD Unit, Gastroenterology Department, University Hospital of Santiago de Compostela, 15706 Santiago, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3758-4540","authenticated-orcid":false,"given":"Zeljko","family":"Krznaric","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Nutrition, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}]},{"given":"Fernando","family":"Magro","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Centro Hospitalar S\u00e3o Jo\u00e3o, 4200319 Porto, Portugal"}]},{"given":"Konstantinos","family":"Karmiris","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Venizeleion General Hospital, Heraklion, 71409 Crete, Greece"}]},{"given":"Tim","family":"Raine","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Addenbrooke\u2019s Hospital, Cambridge University Hospitals, Cambridge CB2 0QQ, UK"}]},{"given":"David","family":"Drobne","sequence":"additional","affiliation":[{"name":"University Medical Centre Ljubljana, Department of Gastroenterology, Medical Faculty, University of Ljubljana, 1231 Ljubljana, Slovenia"}]},{"given":"Ioannis","family":"Koutroubakis","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital of Heraklion, 71500 Crete, Greece"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9275-4242","authenticated-orcid":false,"given":"Maria","family":"Chaparro","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Hospital Universitario de La Princesa, Instituto de Investigaci\u00f3n Sanitaria Princesa (IIS-IP), Universidad Aut\u00f3noma de Madrid, 28001 Madrid, Spain"}]},{"given":"Henit","family":"Yanai","sequence":"additional","affiliation":[{"name":"IBD Center, Division of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 49100, Israel"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-5139","authenticated-orcid":false,"given":"Johan","family":"Burisch","sequence":"additional","affiliation":[{"name":"Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, 2650 Copenhagen, Denmark"}]},{"given":"Uri","family":"Kopylov","sequence":"additional","affiliation":[{"name":"Sheba Medical Center, Department of Gastroenterology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 52621, Israel"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/apt.14452","article-title":"Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn\u2019s disease who lose clinical response","volume":"47","author":"Dreesen","year":"2017","journal-title":"Aliment. 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