{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:53:28Z","timestamp":1790855608657,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["UEG Journal"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>The availability of biological agents for inflammatory bowel disease has increased over the past years. In this systematic review and meta\u2010analysis, we aimed to explore time trends in clinical response and clinical remission rates in Crohn's disease (CD) patients treated with biologics while discussing the need for new strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MEDLINE, Cochrane, and ISI Web of Science databases were searched for randomized placebo\u2010controlled trials with biological agents in moderate\u2010to\u2010severe CD patients. Sub\u2010group and meta\u2010regression analyses compared treatment and placebo by calculating the pooled odds ratios of clinical remission and clinical response, across time categories and publication year. We also estimated the proportion of patients achieving clinical remission and clinical response by comparing both groups according to the publication year.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010five trials were included in the systematic review, which enrolled 8879 patients between 1997 and 2022. The clinical remission and clinical response odds, in induction and maintenance, have been constant over time, as no statistically significant differences were found between time categories (interaction <jats:italic>p<\/jats:italic>\u2010values: clinical remission [induction, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.19; maintenance, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.24]; clinical response [induction, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.43; maintenance, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.59]). In meta\u2010regression analyses, publication year did not influence these outcomes (clinical remission [induction, OR 1.01{95% CI 0.97\u20131.05}, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.72; clinical response [induction, OR 1.01{95% CI 0.97\u20131.04]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.63; maintenance, OR 1.03{95% CI 0.98\u20131.07}; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.21]), with the exception of clinical remission in maintenance studies, which presented a decreased effect (odds ratio 0.97{95% CI 0.94\u20131.00}, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.03]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our review highlights that the odds of clinical outcomes in CD patients receiving biological treatment relative to placebo have been stable in the last decades.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ueg2.12366","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T10:45:07Z","timestamp":1678099507000},"page":"202-217","source":"Crossref","is-referenced-by-count":31,"title":["Has the therapeutical ceiling been reached in Crohn's disease randomized controlled trials? A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2634-9668","authenticated-orcid":false,"given":"Fernando","family":"Magro","sequence":"first","affiliation":[{"name":"Department of Gastroenterology S\u00e3o Jo\u00e3o University Hospital Center  Porto Portugal"},{"name":"Clinical Pharmacology Unit S\u00e3o Jo\u00e3o University Hospital Center  Porto Portugal"},{"name":"Department of Biomedicine Unit of Pharmacology and Therapeutics Faculty of Medicine University of Porto  Porto Portugal"},{"name":"CINTESIS\u2014Center for Health Technology and Services Research  Porto Portugal"},{"name":"RISE\u2014Health Research Network  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Le\u00e3o","family":"Moreira","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit S\u00e3o Jo\u00e3o University Hospital Center  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Catalano","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Vita\u2010Salute San Raffaele  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Alves","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5098-8729","authenticated-orcid":false,"given":"Joana","family":"Roseira","sequence":"additional","affiliation":[{"name":"Gastroenterology Department Algarve University Hospital Center  Faro Portugal"},{"name":"ABC\u2014Algarve Biomedical Center  Loul\u00e9 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7171-0139","authenticated-orcid":false,"given":"Maria Manuela","family":"Estevinho","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Centro Hospitalar de Vila Nova de Gaia\/Espinho EPE  Vila Nova de Gaia Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Silva","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit S\u00e3o Jo\u00e3o University Hospital Center  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9724-054X","authenticated-orcid":false,"given":"Axel","family":"Dignass","sequence":"additional","affiliation":[{"name":"Department of Medicine I Agaplesion Markus Hospital Goethe\u2010University  Frankfurt Am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2536-6618","authenticated-orcid":false,"given":"Laurent","family":"Peyrin\u2010Biroulet","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Inserm NGERE U1256 University Hospital of Nancy University of Lorraine  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Danese","sequence":"additional","affiliation":[{"name":"Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and University Vita\u2010Salute San Raffaele  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Gastroenterology Western University  London Ontario Canada"},{"name":"Lawson Health Research Institute Western University  London Ontario Canada"},{"name":"Department of Epidemiology and Biostatistics Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Camila","family":"Dias","sequence":"additional","affiliation":[{"name":"CINTESIS\u2014Center for Health Technology and Services Research  Porto Portugal"},{"name":"MEDCIDS \u2010 Department of Community Medicine, Information and Health Decision Sciences Faculty of Medicine University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafalda","family":"Santiago","sequence":"additional","affiliation":[{"name":"CINTESIS\u2014Center for Health Technology and Services Research  Porto Portugal"},{"name":"GEDII\u2014Portuguese Inflammatory Bowel Disease Study Group  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050640615590302"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140\u20106736(93)91375\u2010v"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl16308"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.135"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/mog.0000000000000735"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.18902.1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.04.022"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otac002"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.10.037"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.04.068"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2010.02.007"},{"key":"e_1_2_11_13_1","unstructured":"HigginsJPT ThomasJ ChandlerJ CumpstonM LiT PageMJ WelchVA(editors).Cochrane Handbook for systematic reviews of interventions version 6.3. (updated February 2022)."},{"key":"e_1_2_11_14_1","unstructured":"Critical Appraisal Skills Programme CASP.(Randomised controlled trial) checklist;2022. [online]."},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050640617725668"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050640619854670"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.11.041"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(17)30570\u20106"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(02)08512\u20104"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.02.014"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0016\u20105085(99)70332\u2010x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa067594"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2011.04.031"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.05.008"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa062897"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.06.064"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejm199710093371502"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.01.035"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.030"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.01.047"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535\u2010019\u201001647\u2010w"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2011.07.013"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010146\u201012\u2010200706190\u201000159"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1602773"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1215739"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1203572"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.10.050"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjab133"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102036.2004.02285.x"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102036.2009.04125.x"}],"container-title":["United European Gastroenterology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ueg2.12366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ueg2.12366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ueg2.12366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T08:07:57Z","timestamp":1692691677000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ueg2.12366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/ueg2.12366"],"URL":"https:\/\/doi.org\/10.1002\/ueg2.12366","archive":["Portico"],"relation":{},"ISSN":["2050-6406","2050-6414"],"issn-type":[{"value":"2050-6406","type":"print"},{"value":"2050-6414","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3]]}}}