{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T01:34:26Z","timestamp":1772847266717,"version":"3.50.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and\/or endoscopic outcomes in moderately-to-severely active ulcerative colitis [UC].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Endoscopic remission [ER], histological improvement [HI], histological remission [HR], histological-endoscopic mucosal improvement [HEMI], and histological-endoscopic mucosal remission [HEMR] were assessed at Week [W]12 [LUCENT-1: N\u2005=\u20051162, induction] and W40 [LUCENT-2: N\u2005=\u2005544, maintenance] for patients randomised to mirikizumab or placebo. Analyses were performed to evaluate predictors of: HEMI at W12 with mirikizumab and HEMR at W40 in patients re-randomised to subcutaneous [SC] mirikizumab; associations between W12 histological\/endoscopic endpoints and W40 outcomes in mirikizumab responders re-randomised to mirikizumab SC; and associations between W40 endoscopic normalisation [EN] with\/without HR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Significantly more patients treated with mirikizumab achieved HI, HR, ER, HEMI, and HEMR vs placebo [p\u2005&amp;lt;0.001], irrespective of prior biologic\/tofacitinib failure [p\u2005&amp;lt;0.05]. Lower clinical baseline disease activity, female sex, no baseline immunomodulator use, and no prior biologic\/tofacitinib failure were predictors of HEMI at W12 [p\u2005&amp;lt;0.05]. Corticosteroid use and longer disease duration were negative predictors of achieving HEMR at W40 [p\u2005&amp;lt;0.05]. W12 HI, HR, or ER was associated with W40 HEMI or HEMR [p\u2005&amp;lt;0.05]; ER at W12 was associated with clinical remission [CR] [p\u2005&amp;lt;0.05] and corticosteroid-free remission [CSFR] at W40 [p\u2005=\u20050.052]. HR and HEMR at W12 were associated with CSFR, CR, and symptomatic remission at W40. Alternate HEMR [EN\u2005+\u2005HR] at W40 was associated with bowel urgency remission at W40 [p\u2005&amp;lt;0.05].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Early resolution of endoscopic and histological inflammation with mirikizumab is associated with better UC outcomes. Clinicaltrials.gov: LUCENT-1, NCT03518086; LUCENT-2, NCT03524092.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjad050","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T11:54:37Z","timestamp":1681473277000},"page":"1457-1470","source":"Crossref","is-referenced-by-count":31,"title":["Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2634-9668","authenticated-orcid":false,"given":"Fernando","family":"Magro","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, University Hospital S\u00e3o Jo\u00e3o , Porto , Portugal"},{"name":"CINTESIS@RISE - Health Research Network, Faculty of Medicine, University of Porto , Porto , Portugal"}]},{"given":"Rish K","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Scottsdale, AZ , USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2073-4234","authenticated-orcid":false,"given":"Taku","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital , Minato-ku, Tokyo , Japan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8603-898X","authenticated-orcid":false,"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Western University , London, ON , Canada"},{"name":"Alimentiv Inc. , London, ON , Canada"},{"name":"Department of Epidemiology and Biostatistics, Western University , London, ON , Canada"}]},{"given":"Florian","family":"Rieder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation , Cleveland, OH , USA"},{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland, OH , USA"}]},{"given":"Isabel","family":"Redondo","sequence":"additional","affiliation":[{"name":"Eli Lilly Portugal, Produtos Farmac\u00eauticos Lda., Lisbon , Portugal"}]},{"given":"Trevor","family":"Lissoos","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN , USA"}]},{"given":"Nathan","family":"Morris","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN , USA"}]},{"given":"Mingyang","family":"Shan","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN , USA"}]},{"given":"Meekyong","family":"Park","sequence":"additional","affiliation":[{"name":"TechData Service Company LLC , Philadelphia, PA , USA"}]},{"given":"Laurent","family":"Peyrin-Biroulet","sequence":"additional","affiliation":[{"name":"University of Lorraine, Inserm, NGERE, Nancy, and Groupe Hospitalier Priv\u00e9 Ambroise Par\u00e9 - Hartmann, Paris IBD Center , Neuilly sur Seine , France"}]}],"member":"286","published-online":{"date-parts":[[2023,4,14]]},"reference":[{"key":"2023102016292405200_CIT0001","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41572-020-0205-x","article-title":"Ulcerative colitis","volume":"6","author":"Kobayashi","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2023102016292405200_CIT0002","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s11938-014-0044-5","article-title":"Ulcerative colitis: what is the optimal treatment goal and how do we achieve it","volume":"13","author":"Ho","year":"2015","journal-title":"Curr Treat Options Gastroenterol"},{"key":"2023102016292405200_CIT0003","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1053\/j.gastro.2006.12.038","article-title":"A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis","volume":"132","author":"D\u2019Haens","year":"2007","journal-title":"Gastroenterology"},{"key":"2023102016292405200_CIT0004","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1365-2036.2011.04701.x","article-title":"Review article: defining remission in ulcerative colitis","volume":"34","author":"Travis","year":"2011","journal-title":"Aliment Pharmacol Ther"},{"key":"2023102016292405200_CIT0005","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1053\/j.gastro.2020.12.031","article-title":"STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease [STRIDE] initiative of the International Organization for the Study of IBD [IOIBD]: determining therapeutic goals for treat-to-target strategies in IBD","volume":"160","author":"Turner","year":"2021","journal-title":"Gastroenterology"},{"key":"2023102016292405200_CIT0006","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1093\/ecco-jcc\/jjaa110","article-title":"ECCO position paper: harmonisation of the approach to ulcerative colitis histopathology","volume":"14","author":"Magro","year":"2020","journal-title":"J Crohns Colitis"},{"key":"2023102016292405200_CIT0007","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/j.cgh.2017.02.016","article-title":"Histologic normalization occurs in ulcerative colitis and is associated with improved clinical outcomes","volume":"15","author":"Christensen","year":"2017","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023102016292405200_CIT0008","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1053\/j.gastro.2011.06.054","article-title":"Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis","volume":"141","author":"Colombel","year":"2011","journal-title":"Gastroenterology"},{"key":"2023102016292405200_CIT0009","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1136\/gutjnl-2015-309598","article-title":"Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up","volume":"65","author":"Bryant","year":"2016","journal-title":"Gut"},{"key":"2023102016292405200_CIT0010","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1016\/j.cgh.2020.09.017","article-title":"Histologic features of colon biopsies [Geboes Score] associated with progression of ulcerative colitis for the first 36 months after biopsy","volume":"19","author":"Magro","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023102016292405200_CIT0011","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1053\/j.gastro.2020.08.037","article-title":"Relationship between combined histologic and endoscopic endpoints and efficacy of ustekinumab treatment in patients with ulcerative colitis","volume":"159","author":"Li","year":"2020","journal-title":"Gastroenterology"},{"key":"2023102016292405200_CIT0012","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1053\/j.gastro.2020.06.043","article-title":"Incremental benefit of achieving endoscopic and histologic remission in patients with ulcerative colitis: a systematic review and meta-analysis","volume":"159","author":"Yoon","year":"2020","journal-title":"Gastroenterology"},{"key":"2023102016292405200_CIT0013","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1097\/MEG.0000000000000378","article-title":"Characterizing unmet medical need and the potential role of new biologic treatment options in patients with ulcerative colitis and Crohn\u2019s disease: a systematic review and clinician surveys","volume":"27","author":"Gordon","year":"2015","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"2023102016292405200_CIT0014","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.3748\/wjg.v21.i11.3282","article-title":"Real-life outcome of anti-tumor necrosis factor alpha in the ambulatory treatment of ulcerative colitis","volume":"21","author":"Baki","year":"2015","journal-title":"World J Gastroenterol"},{"key":"2023102016292405200_CIT0015","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1053\/j.gastro.2019.08.043","article-title":"Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with ulcerative colitis","volume":"158","author":"Sandborn","year":"2020","journal-title":"Gastroenterology"},{"key":"2023102016292405200_CIT0016","doi-asserted-by":"crossref","first-page":"297645","DOI":"10.1155\/2009\/297645","article-title":"Interleukin-23 and Th17 cells in the control of gut inflammation","volume":"2009","author":"Monteleone","year":"2009","journal-title":"Mediators Inflamm"},{"key":"2023102016292405200_CIT0017","article-title":"Mirikizumab as induction and maintenance therapy for ulcerative colitis","author":"D\u2019Haens","year":"2022","journal-title":"N Engl J Med"},{"key":"2023102016292405200_CIT0018","first-page":"305","article-title":"A simplified Geboes score for ulcerative colitis","volume":"11","author":"Jauregui-Amezaga","year":"2017","journal-title":"J Crohns Colitis"},{"key":"2023102016292405200_CIT0019","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1016\/j.cgh.2019.12.011","article-title":"Complete resolution of mucosal neutrophils associates with improved long-term clinical outcomes of patients with ulcerative colitis","volume":"18","author":"Pai","year":"2020","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023102016292405200_CIT0020","doi-asserted-by":"crossref","first-page":"e1509","DOI":"10.1016\/j.cgh.2021.08.003","article-title":"Epithelial neutrophilic infiltrate: the rising star in ulcerative colitis","volume":"20","author":"Estevinho","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023102016292405200_CIT0021","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1053\/j.gastro.2021.02.035","article-title":"An international consensus to standardize integration of histopathology in ulcerative colitis clinical trials","volume":"160","author":"Ma","year":"2021","journal-title":"Gastroenterology"},{"key":"2023102016292405200_CIT0022","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.cgh.2021.07.005","article-title":"Early change in epithelial neutrophilic infiltrate predicts long-term response to biologics in ulcerative colitis","volume":"20","author":"Narula","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023102016292405200_CIT0023","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.cgh.2020.07.012","article-title":"Combination therapy does not improve rate of clinical or endoscopic remission in patients with inflammatory bowel diseases treated with vedolizumab or ustekinumab","volume":"19","author":"Hu","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023102016292405200_CIT0024","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.cgh.2020.06.071","article-title":"No benefit of concomitant immunomodulator therapy on efficacy of biologics that are not tumor necrosis factor antagonists in patients with inflammatory bowel diseases: a meta-analysis","volume":"19","author":"Yzet","year":"2021","journal-title":"Clin Gastroenterol Hepatol"}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/advance-article-pdf\/doi\/10.1093\/ecco-jcc\/jjad050\/51715993\/jjad050.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/17\/9\/1457\/52307957\/jjad050.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/17\/9\/1457\/52307957\/jjad050.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T18:20:59Z","timestamp":1697826059000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/17\/9\/1457\/7119064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,14]]},"references-count":24,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,4,14]]},"published-print":{"date-parts":[[2023,10,20]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjad050","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,9,1]]},"published":{"date-parts":[[2023,4,14]]}}}