{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:58:17Z","timestamp":1786114697879,"version":"build-2736575974"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100024017","name":"Sheba Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100024017","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mucosal healing (MH) is associated with improved long-term outcomes in Crohn\u2019s disease (CD), but longitudinal pan-enteric data are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective observational study enrolled adults with CD initiating first-line biologic who were assessed at weeks 0, 14, 26, 52, 78, and 104 using fecal calprotectin (FCP), intestinal ultrasound (IUS), and pan-enteric video capsule endoscopy (VCE). The primary outcome was biologic discontinuation for any reason within 104\u2009weeks. Secondary outcomes included MH (Lewis score\u2009&amp;lt;\u2009135 and Eliakim score\u2009=\u20090) and flare-driven biologic discontinuation. Analyses used generalized estimating equations (GEE), Kaplan\u2013Meier, and Cox models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 59 patients (median age-30 [23-43] years, male-52.5%, inflammatory phenotype-79.7%), 35 received anti-TNF, 21 vedolizumab, and 3 ustekinumab. Overall, 29 (49.2%) patients discontinued biologics after 39 (28-52) weeks, including 21 (35.6%) flare-driven discontinuations. With non-responder imputation, pan-enteric MH increased from 3.4% to 16.9%, 18.6%, and 32.2% at weeks 14, 52, and 104 (P\u2009&amp;lt;\u2009.001), consistent on observed-data GEE. Week-14 log-transformed FCP was most strongly associated with week-52 MH (area under the curve 0.804, 95% CI, 0.685-0.923, P\u2009=\u2009.002, optimal cutoff 172\u2009mcg\/g; lagged GEE odds ratio [OR] 0.59, 0.39-0.89, P\u2009=\u2009.012), whereas same-visit transmural remission (bowel wall thickness\u2009\u2264\u20093mm) showed the strongest association with MH (OR 4.97, 1.91-12.91, P\u2009=\u2009.001). Week-14 Lewis score\u2009\u2265\u2009350 (Hazard ratio [HR] 3.18, 95% CI, 1.16-8.73, P\u2009=\u2009.025) and perianal disease (HR 3.93, 95% CI, 1.45-10.62, P\u2009=\u2009.007) were independently associated with flare-driven discontinuation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pan-enteric MH accrues incrementally beyond year 1. Integrated FCP, IUS, and VCE assessments may optimize individualized biologic decisions in CD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjag118","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:48:26Z","timestamp":1784116106000},"source":"Crossref","is-referenced-by-count":0,"title":["Multimodal monitoring of pan-enteric mucosal healing and biologic persistence in Crohn\u2019s disease\u2014the MILESTONE-CD prospective cohort"],"prefix":"10.1093","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8601-6550","authenticated-orcid":false,"given":"Offir","family":"Ukashi","sequence":"first","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8962-4263","authenticated-orcid":false,"given":"Ahmad","family":"Albshesh","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Ungar","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Varon","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]},{"name":"Department of Diagnostic Imaging, Sheba Medical Center , Ramat Gan,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadar","family":"Levy","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi Talan","family":"Asher","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moran","family":"Goren","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Haj","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asaf","family":"Zlotnik","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]},{"name":"Department of Internal Medicine, Sheba Medical Center , Ramat Gan,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Zimlichman","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]},{"name":"ARC Innovation, Sheba Medical Center , Ramat Gan,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Eliakim","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shomron","family":"Ben-Horin","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7156-0588","authenticated-orcid":false,"given":"Uri","family":"Kopylov","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center , Tel Hashomer,","place":["Israel"]},{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"issue":"Suppl 2","key":"2026080517253418900_jjag118-B1","doi-asserted-by":"publisher","first-page":"S54","DOI":"10.1002\/ibd.20561","article-title":"Does the behavior of Crohn\u2019s disease change over time?","volume":"14","author":"Louis","year":"2008","journal-title":"Inflamm Bowel Dis"},{"key":"2026080517253418900_jjag118-B2","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1053\/j.gastro.2010.06.070","article-title":"Risk factors associated with progression to intestinal complications of Crohn\u2019s disease in a population-based cohort","volume":"139","author":"Thia","year":"2010","journal-title":"Gastroenterology"},{"key":"2026080517253418900_jjag118-B3","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1053\/j.gastro.2016.10.005","article-title":"Advances in use of endoscopy, radiology, and biomarkers to monitor inflammatory bowel diseases","volume":"152","author":"Panes","year":"2017","journal-title":"Gastroenterology"},{"key":"2026080517253418900_jjag118-B4","doi-asserted-by":"publisher","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":"2026080517253418900_jjag118-B5","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/S2468-1253(24)00034-7","article-title":"A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn\u2019s disease (PROFILE): a multicentre, open-label randomised controlled trial","volume":"9","author":"Noor","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2026080517253418900_jjag118-B6","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1093\/ibd\/izad149","article-title":"Early biologic treatment decreases risk of surgery in Crohn\u2019s disease but not in ulcerative colitis: systematic review and meta-analysis","volume":"30","author":"Law","year":"2024","journal-title":"Inflamm Bowel Dis"},{"key":"2026080517253418900_jjag118-B7","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1097\/MOG.0000000000000830","article-title":"Small bowel Crohn\u2019s disease: optimal modality for diagnosis and monitoring","volume":"38","author":"Carretero","year":"2022","journal-title":"Curr Opin Gastroenterol"},{"key":"2026080517253418900_jjag118-B8","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.giec.2024.07.002","article-title":"Capsule endoscopy in inflammatory bowel disease: evolving role and recent advances","volume":"35","author":"Eidler","year":"2025","journal-title":"Gastrointest Endosc Clin N Am"},{"key":"2026080517253418900_jjag118-B9","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1080\/00365521.2021.2018491","article-title":"Assessment of endoscopic response using pan-enteric capsule endoscopy in Crohn\u2019s disease; the Sensitivity to Change (STOC) study","volume":"57","author":"Volkers","year":"2022","journal-title":"Scand J Gastroenterol"},{"key":"2026080517253418900_jjag118-B10","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1093\/ibd\/izae254","article-title":"Assessment of treatment response in known Crohn\u2019s disease-a prospective blinded study comparing the diagnostic accuracy of intestinal ultrasound, magnetic resonance enterocolonography, panenteric capsule endoscopy, and fecal calprotectin","volume":"31","author":"Brodersen","year":"2025","journal-title":"Inflamm Bowel Dis"},{"key":"2026080517253418900_jjag118-B11","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1002\/ueg2.70103","article-title":"Vedolizumab achieves pan-enteric mucosal healing in Crohn\u2019s disease: a prospective observational study","volume":"13","author":"Ukashi","year":"2025","journal-title":"United European Gastroenterol J. Published J"},{"key":"2026080517253418900_jjag118-B12","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1093\/ibd\/izae296","article-title":"Intestinal ultrasound measures are strongly correlated with small bowel endoscopic lewis score in active Crohn\u2019s disease","volume":"31","author":"Ukashi","year":"2025","journal-title":"Inflamm Bowel Dis"},{"key":"2026080517253418900_jjag118-B13","doi-asserted-by":"publisher","first-page":"9657053","DOI":"10.1155\/2016\/9657053","article-title":"Clinical experience with the PillCam patency capsule prior to video capsule endoscopy: a real-world experience. Chun HJ, ed","volume":"2016","author":"R\u00f6mmele","year":"2016","journal-title":"Gastroenterol Res Pract"},{"key":"2026080517253418900_jjag118-B14","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/j.1365-2036.2007.03556.x","article-title":"Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change","volume":"27","author":"Gralnek","year":"2008","journal-title":"Aliment Pharmacol Ther"},{"key":"2026080517253418900_jjag118-B15","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1093\/ecco-jcc\/jjae068","article-title":"Pan-enteric Crohn\u2019s capsule [Eliakim] score reliability and responsiveness to change in active Crohn\u2019s disease","volume":"18","author":"Ukashi","year":"2024","journal-title":"J Crohns Colitis"},{"key":"2026080517253418900_jjag118-B16","doi-asserted-by":"publisher","first-page":"17562848251343008","DOI":"10.1177\/17562848251343008","article-title":"Intestinal ultrasound measurement of bowel wall thickness can be used as a sole marker for defining anti-TNF maintenance therapy failure in Crohn\u2019s disease","volume":"18","author":"Albshesh","year":"2025","journal-title":"Ther Adv Gastroenterol"},{"issue":"Suppl A","key":"2026080517253418900_jjag118-B17","doi-asserted-by":"publisher","first-page":"5A","DOI":"10.1155\/2005\/269076","article-title":"Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology","volume":"19","author":"Silverberg","year":"2005","journal-title":"Can J Gastroenterol."},{"key":"2026080517253418900_jjag118-B18","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/S2468-1253(19)30088-3","article-title":"Assessment of small bowel mucosal healing by video capsule endoscopy for the prediction of short-term and long-term risk of Crohn\u2019s disease flare: a prospective cohort study","volume":"4","author":"Ben-Horin","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2026080517253418900_jjag118-B19","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1053\/j.gastro.2025.02.031","article-title":"Capsule endoscopy-guided proactive treat-to-target versus continued standard care in patients with quiescent Crohn\u2019s disease: a randomized controlled trial","volume":"169","author":"Ben-Horin","year":"2025","journal-title":"Gastroenterology."},{"key":"2026080517253418900_jjag118-B20","doi-asserted-by":"publisher","first-page":"603","DOI":"10.5152\/tjg.2023.22527","article-title":"Mucosal healing and clinical efficacy of adalimumab in Small Intestinal Crohn\u2019s Disease (SIMCHA Study): final results from a prospective, open-label, single-arm study","volume":"34","author":"Wetwittayakhlang","year":"2023","journal-title":"Turk J Gastroenterol"},{"key":"2026080517253418900_jjag118-B21","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1093\/ibd\/izad173","article-title":"A treat-to-target strategy guided by pan-enteric evaluation in children with Crohn\u2019s disease improves outcomes at 2 years","volume":"30","author":"D\u2019Arcangelo","year":"2024","journal-title":"Inflamm Bowel Dis"},{"key":"2026080517253418900_jjag118-B22","doi-asserted-by":"publisher","first-page":"17562848231159452","DOI":"10.1177\/17562848231159452","article-title":"Is there an optimal sequence of biologic therapies for inflammatory bowel disease?","volume":"16","author":"Bressler","year":"2023","journal-title":"Ther Adv Gastroenterol"},{"key":"2026080517253418900_jjag118-B23","doi-asserted-by":"publisher","first-page":"2779","DOI":"10.1016\/S0140-6736(17)32641-7","article-title":"Effect of tight control management on Crohn\u2019s disease (CALM): a multicentre, randomised, controlled phase 3 trial","volume":"390","author":"Colombel","year":"2017","journal-title":"Lancet"},{"key":"2026080517253418900_jjag118-B24","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.cgh.2019.05.029","article-title":"Monitoring a combination of calprotectin and infliximab identifies patients with mucosal healing of Crohn\u2019s disease","volume":"18","author":"Dreesen","year":"2020","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2026080517253418900_jjag118-B25","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjae123","article-title":"Fecal calprotectin diagnostic level gradient along the small bowel in patients with Crohn\u2019s disease","author":"Ukashi","journal-title":"J Crohns Colitis"},{"key":"2026080517253418900_jjag118-B26","doi-asserted-by":"publisher","first-page":"102559","DOI":"10.1016\/j.eclinm.2024.102559","article-title":"Ultrasound remission after biologic induction and long-term endoscopic remission in Crohn\u2019s disease: a prospective cohort study","volume":"71","author":"Allocca","year":"2024","journal-title":"EClinicalMedicine"},{"key":"2026080517253418900_jjag118-B27","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1093\/ecco-jcc\/jjac072","article-title":"Intestinal ultrasound early on in treatment follow-up predicts endoscopic response to anti-TNF\u03b1 treatment in Crohn\u2019s disease","volume":"16","author":"de Voogd","year":"2022","journal-title":"J Crohns Colitis"},{"key":"2026080517253418900_jjag118-B28","doi-asserted-by":"publisher","first-page":"308","DOI":"10.14366\/usg.25079","article-title":"How to use intestinal ultrasonography in patients with Crohn disease: its role in the assessment of disease activity and disease monitoring in the era of the treat-to-target strategy","volume":"44","author":"You","year":"2025","journal-title":"Ultrasonography"},{"key":"2026080517253418900_jjag118-B29","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgast-2019-000365","article-title":"Panenteric capsule endoscopy versus ileocolonoscopy plus magnetic resonance enterography in Crohn\u2019s disease: a multicentre, prospective study","author":"Bruining","journal-title":"BMJ Open Gastroenterol"},{"key":"2026080517253418900_jjag118-B30","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.2147\/PPA.S99690","article-title":"Magnetic resonance enterography or video capsule endoscopy\u2014what do Crohn\u2019s disease patients prefer?","volume":"10","author":"Lahat","year":"2016","journal-title":"Patient Prefer Adherence"},{"key":"2026080517253418900_jjag118-B31","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.221","article-title":"Detection of small bowel mucosal healing and deep remission in patients with known small bowel Crohn\u2019s disease using biomarkers, capsule endoscopy, and imaging","volume-title":"Am J Gastroenterol","author":"Kopylov","year":"2015"}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/20\/8\/jjag118\/70500538\/jjag118.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/20\/8\/jjag118\/70500538\/jjag118.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T21:25:38Z","timestamp":1785965138000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/doi\/10.1093\/ecco-jcc\/jjag118\/8752925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,5]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjag118","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,8]]},"article-number":"jjag118"}}