Histologic assessments in ulcerative colitis: the evidence behind a new endpoint in clinical trials

References

• Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis. Lancet (London, England). 2017 Apr 29;389(10080):1756–1770. doi: 10.1016/S0140-6736(16)32126-2
   PubMed Web of Science ®Google Scholar
• Dignass A, Eliakim R, Magro F, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohn’s & Colitis. 2012 Dec;6(10):965–990.
   PubMed Web of Science ®Google Scholar
• Kobayashi T, Siegmund B, Le Berre C, et al. Ulcerative colitis. Nat Rev Dis Primers. 2020 Sep 10;6(1):74. doi: 10.1038/s41572-020-0205-x
   PubMed Web of Science ®Google Scholar
• Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011 Nov 3;365(18):1713–1725. doi: 10.1056/NEJMra1102942
   PubMed Web of Science ®Google Scholar
• Lamb CA, Kennedy NA, Raine T, et al. British society of gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019 Dec;68(Suppl 3):s1–s106.
   PubMed Web of Science ®Google Scholar
• Feuerstein JD, Cheifetz AS. Ulcerative colitis: epidemiology, diagnosis, and management. Mayo Clin Proc. 2014 Nov;89(11):1553–1563. doi: 10.1016/j.mayocp.2014.07.002
   PubMed Web of Science ®Google Scholar
• Peyrin-Biroulet L, Panés J, Sandborn WJ, et al. Defining disease severity in inflammatory bowel diseases: current and future directions. Clin Gastroenterol Hepatol. 2016 Mar;14(3):348–354.e17.
   PubMed Web of Science ®Google Scholar
• Yarlas A, Willian MK, Nag A. The impact of clinical symptoms and endoscopic and histologic disease activity on health-related quality of life in patients with ulcerative colitis following treatment with multimatrix mesalazine. Quality of life research: an international journal of quality of life aspects of treatment, care and rehabilitation. Qual Life Res. 2021 Jul;30(7):1925–1938. doi: 10.1007/s11136-021-02787-4
   PubMed Web of Science ®Google Scholar
• Yarlas A, Rubin DT, Panés J, et al. Burden of ulcerative colitis on functioning and well-being: a systematic literature review of the SF-36® health survey. J Crohn’s & Colitis. 2018 Apr 27;12(5):600–609. doi: 10.1093/ecco-jcc/jjy024
   PubMed Web of Science ®Google Scholar
• Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384–413.
   PubMed Web of Science ®Google Scholar
• Feuerstein JD, Isaacs KL, Schneider Y, et al. AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020 Apr;158(5):1450–1461.
   PubMed Web of Science ®Google Scholar
• Singh S, Allegretti JR, Siddique SM, et al. AGA technical review on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020 Apr;158(5):1465–1496.e17.
   PubMed Web of Science ®Google Scholar
• Levesque BG, Sandborn WJ, Ruel J, et al. Converging goals of treatment of inflammatory bowel disease from clinical trials and practice. Gastroenterology. 2015 Jan;148(1):37–51.e1.
   PubMed Web of Science ®Google Scholar
• Mosli MH, Parker CE, Nelson SA, et al. Histologic scoring indices for evaluation of disease activity in ulcerative colitis. Cochrane Database Syst Rev. 2017 May 25;5(5):Cd011256. doi: 10.1002/14651858.CD011256.pub2
   PubMedGoogle Scholar
• Yoon H, Jangi S, Dulai PS, et al. Incremental benefit of achieving endoscopic and histologic remission in patients with ulcerative colitis: a systematic review and meta-analysis. Gastroenterology. 2020 Oct;159(4):1262–1275.e7.
   PubMed Web of Science ®Google Scholar
• Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015 Sep;110(9):1324–38.
   PubMed Web of Science ®Google Scholar
• Colombel JF, D’Haens G, Lee WJ, et al. Outcomes and strategies to support a treat-to-target approach in inflammatory bowel disease: a systematic review. J Crohn’s & Colitis. 2020 Feb 10;14(2):254–266. doi: 10.1093/ecco-jcc/jjz131
   PubMed Web of Science ®Google Scholar
• Dal Buono A, Roda G, Argollo M, et al. Treat to target or ‘treat to clear’ in inflammatory bowel diseases: one step further? Expert review of gastroenterology & hepatology. Exp Rev Gastroenterol Hepatol. 2020 Sep;14(9):807–817.
   PubMedGoogle Scholar
• Wetwittayakhlang P, Lontai L, Gonczi L, et al. Treatment targets in ulcerative colitis: is it time for all In, including histology? J Clin Med. 2021 Nov 26;10(23):5551. doi: 10.3390/jcm10235551
   PubMed Web of Science ®Google Scholar
• Ulcerative Colitis: Clinical Trial Endpoints. Draft Guidance for Industry. (CDER) CfDEaR. editor. 2016.
   Google Scholar
• Ungaro R, Colombel JF, Lissoos T, et al. A treat-to-target update in ulcerative colitis: a systematic review. Am J Gastroenterol. 2019 Jun;114(6):874–883.
   PubMed Web of Science ®Google Scholar
• Turner D, Ricciuto A, Lewis A, et al. 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. Gastroenterology. 2021 Apr;160(5):1570–1583.
   PubMed Web of Science ®Google Scholar
• Danese S, Roda G, Peyrin-Biroulet L. Evolving therapeutic goals in ulcerative colitis: towards disease clearance. Nat Rev Gastroenterol Hepatol. 2020 Jan;17(1):1–2. doi: 10.1038/s41575-019-0211-1
   PubMed Web of Science ®Google Scholar
• Schreiber S, Danese S, Dignass A, et al. Defining comprehensive disease control for use as a treatment target for ulcerative colitis in clinical practice: international delphi consensus recommendations. J Crohn’s & Colitis. 2023 Aug 16;17(Supplement_1):i311–i312. doi: 10.1093/ecco-jcc/jjac190.0281
   PubMedGoogle Scholar
• Bhattacharya S, Cross RK. Is endoscopic remission in ulcerative colitis still good enough? Inflammatory bowel diseases. Inflamm Bowel Dis. 2019 Oct 18;25(11):1729–1730.
   PubMed Web of Science ®Google Scholar
• Bryant RV, Burger DC, Delo J, et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2016 Mar;65(3):408–414.
   PubMed Web of Science ®Google Scholar
• Pai RK, Lauwers GY, Pai RK. Measuring histologic activity in inflammatory bowel disease: why and how. Advances in anatomic pathology. Adv Anat Pathol. 2022 Jan 1;29(1):37–47.
   PubMed Web of Science ®Google Scholar
• Bessissow T, Kron CM, Marcus V, et al. Impact of endoscopic and histologic activity on disease relapse in ulcerative colitis. Am J Gastroenterol. 2022 Oct 1;117(10):1632–1638. doi: 10.14309/ajg.0000000000001912
   PubMed Web of Science ®Google Scholar
• Gupta A, Yu A, Peyrin-Biroulet L, et al. Treat to target: the role of histologic healing in inflammatory bowel diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2021 Sep;19(9):1800–1813.e4.
   PubMed Web of Science ®Google Scholar
• Pai RK, Geboes K. Disease activity and mucosal healing in inflammatory bowel disease: a new role for histopathology? Virchows Arch. 2018 Jan;472(1):99–110. doi: 10.1007/s00428-017-2156-5
   PubMed Web of Science ®Google Scholar
• Magro F, Doherty G, Peyrin-Biroulet L, et al. ECCO position paper: harmonization of the approach to ulcerative colitis histopathology. J Crohn’s & Colitis. 2020 Nov 7;14(11):1503–1511. doi: 10.1093/ecco-jcc/jjaa110
   PubMed Web of Science ®Google Scholar
• D’Haens G, Sandborn WJ, Feagan BG, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007 Feb;132(2):763–786.
   PubMed Web of Science ®Google Scholar
• de Jong MJ, Huibregtse R, Masclee AAM, et al. Patient-reported outcome measures for use in clinical trials and clinical practice in inflammatory bowel diseases: a systematic review. Clin Gastroenterol Hepatol. 2018 May;16(5):648–663.e3.
   PubMed Web of Science ®Google Scholar
• Dubinsky M, Bleakman AP, Panaccione R, et al. Bowel urgency in ulcerative colitis: current perspectives and future directions. Am J Gastroenterol. 2023 Aug 4;118(11):1940–1953. doi: 10.14309/ajg.0000000000002404
   PubMed Web of Science ®Google Scholar
• Pakpoor J, Travis S. Why studying urgency is urgent. Gastroenterol & Hepatol. 2023 Feb;19(2):95–100.
   Google Scholar
• Pai RK, Jairath V, Vande Casteele N, et al. The emerging role of histologic disease activity assessment in ulcerative colitis. Gastrointest Endosc. 2018 Dec;88(6):887–898.
   PubMed Web of Science ®Google Scholar
• Rath T, Atreya R, Neurath MF. Is histological healing a feasible endpoint in ulcerative colitis? Expert review of gastroenterology & hepatology. Exp Rev Gastroenterol Hepatol. 2021 Jun;15(6):665–674. doi: 10.1080/17474124.2021.1880892
   PubMed Web of Science ®Google Scholar
• Feakins RM. Inflammatory bowel disease biopsies: updated British Society of Gastroenterology reporting guidelines. J Clin Pathol. 2013 Dec;66(12):1005–1026. doi: 10.1136/jclinpath-2013-201885
   PubMed Web of Science ®Google Scholar
• Magro F, Langner C, Driessen A, et al. European consensus on the histopathology of inflammatory bowel disease. J Crohn’s & Colitis. 2013 Nov;7(10):827–851.
   PubMed Web of Science ®Google Scholar
• DeRoche TC, Xiao SY, Liu X. Histological evaluation in ulcerative colitis. Gastroenterol Rep (Oxf). 2014 Aug;2(3):178–192. doi: 10.1093/gastro/gou031
   PubMedGoogle Scholar
• Vespa E, D’Amico F, Sollai M, et al. Histological scores in patients with inflammatory bowel diseases: the state of the art. J Clin Med. 2022 Feb 11;11(4):939. doi: 10.3390/jcm11040939
   PubMed Web of Science ®Google Scholar
• Ma C, Sedano R, Almradi A, et al. An international consensus to standardize integration of histopathology in ulcerative colitis clinical trials. Gastroenterology. 2021 Jun;160(7):2291–2302.
   PubMed Web of Science ®Google Scholar
• Villanacci V, Antonelli E, Geboes K, et al. Histological healing in inflammatory bowel disease: a still unfulfilled promise. World J Gastroenterol. 2013 Feb 21;19(7):968–978. doi: 10.3748/wjg.v19.i7.968
   PubMed Web of Science ®Google Scholar
• Li K, Marano C, Zhang H, et al. Relationship between combined histologic and endoscopic endpoints and efficacy of ustekinumab treatment in patients with ulcerative colitis. Gastroenterology. 2020 Dec;159(6):2052–2064.
   PubMed Web of Science ®Google Scholar
• Pai RK, Khanna R, D’Haens GR, et al. Definitions of response and remission for the Robarts Histopathology index. Gut. 2019 Nov;68(11):2101–2102.
   PubMed Web of Science ®Google Scholar
• Peyrin-Biroulet L, Loftus EV Jr., Colombel JF, et al. Histologic outcomes with vedolizumab versus adalimumab in ulcerative colitis: Results from an efficacy and safety study of vedolizumab intravenous compared to adalimumab subcutaneous in participants with ulcerative colitis (VARSITY). Gastroenterology. 2021 Oct;161(4):1156–1167.e3.
   PubMed Web of Science ®Google Scholar
• Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, et al. Development and validation of the Nancy histological index for UC. Gut. 2017 Jan;66(1):43–49.
   PubMed Web of Science ®Google Scholar
• Lang-Schwarz C, Angeloni M, Agaimy A, et al. Validation of the ‘inflammatory bowel disease-distribution, chronicity, activity [IBD-DCA] score’ for ulcerative colitis and Crohn´s disease. J Crohn’s & Colitis. 2021 Oct 7;15(10):1621–1630. doi: 10.1093/ecco-jcc/jjab055
   PubMed Web of Science ®Google Scholar
• Jairath V, Peyrin-Biroulet L, Zou G, et al. Responsiveness of histological disease activity indices in ulcerative colitis: a post hoc analysis using data from the TOUCHSTONE randomised controlled trial. Gut. 2019 Jul;68(7):1162–1168.
   PubMed Web of Science ®Google Scholar
• Magro F, Lopes J, Borralho P, et al. Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels. Gut. 2019 Apr;68(4):594–603.
   PubMed Web of Science ®Google Scholar
• Magro F, Estevinho MM, Dias CC, et al. Clinical, endoscopic and histological outcomes in induction of moderate-to-severe ulcerative colitis: a systematic review with meta-analysis. J Crohn’s & Colitis. 2021 Apr 6;15(4):551–566. doi: 10.1093/ecco-jcc/jjaa176
   PubMed Web of Science ®Google Scholar
• Rath T, Atreya R, Bodenschatz J, et al. Intestinal barrier healing is Superior to endoscopic and histologic remission for predicting major adverse outcomes in inflammatory bowel disease: the prospective ERIca Trial. Gastroenterology. 2022 Oct 21;164(2):241–255. doi: 10.1053/j.gastro.2022.10.014
   PubMed Web of Science ®Google Scholar
• Kishi M, Hirai F, Takatsu N, et al. A review on the current status and definitions of activity indices in inflammatory bowel disease: how to use indices for precise evaluation. J Gastroenterol. 2022 Apr;57(4):246–266.
   PubMed Web of Science ®Google Scholar
• Chateau T, Feakins R, Marchal-Bressenot A, et al. Histological remission in ulcerative colitis: under the microscope is the cure. Am J Gastroenterol. 2020 Feb;115(2):179–189.
   PubMed Web of Science ®Google Scholar
• Geboes K, Riddell R, Ost A, et al. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut. 2000 Sep;47(3):404–409.
   PubMed Web of Science ®Google Scholar
• Mosli MH, Feagan BG, Zou G, et al. Development and validation of a histological index for UC. Gut. 2017 Jan;66(1):50–58
   PubMed Web of Science ®Google Scholar
• Lang-Schwarz C, Agaimy A, Atreya R, et al. Maximizing the diagnostic information from biopsies in chronic inflammatory bowel diseases: recommendations from the Erlangen International Consensus Conference on inflammatory bowel diseases and presentation of the IBD-DCA score as a proposal for a new index for histologic activity assessment in ulcerative colitis and Crohn’s disease. Virchows Arch. 2021 Mar;478(3):581–594.
   PubMed Web of Science ®Google Scholar
• Hindryckx P, Baert F, Hart A, et al. Clinical trials in ulcerative colitis: a historical perspective. J Crohn’s & Colitis. 2015 Jul;9(7):580–8.
   PubMed Web of Science ®Google Scholar
• Pandey A, Achrafie L, Kodjamanova P, et al. Endoscopic mucosal healing and histologic remission in ulcerative colitis: a systematic literature review of clinical, quality-of-life and economic outcomes. Curr Med Res Opin. 2022 Sep;38(9):1531–1541.
   PubMed Web of Science ®Google Scholar
• Mosli MH, Feagan BG, Zou G, et al. Reproducibility of histological assessments of disease activity in UC. Gut. 2015 Nov;64(11):1765–1773.
   PubMed Web of Science ®Google Scholar
• Magro F, Lopes J, Borralho P, et al. Comparison of the Nancy index with continuous geboes score: histological remission and response in ulcerative colitis. J Crohn’s & Colitis. 2020 Jul 30;14(7):1021–1025. doi: 10.1093/ecco-jcc/jjaa010
   PubMed Web of Science ®Google Scholar
• Magro F, Sabino J, Rosini F, et al. ECCO Position on harmonisation of Crohn’s disease mucosal histopathology. J Crohn’s & Colitis. 2022 Jul 14;16(6):876–883. doi: 10.1093/ecco-jcc/jjac006
   PubMed Web of Science ®Google Scholar
• Ma C, Hanzel J, Panaccione R, et al. CORE-IBD: a multidisciplinary international consensus initiative to develop a core outcome set for randomized controlled trials in inflammatory bowel disease. Gastroenterology. 2022 Oct;163(4):950–964.
   PubMed Web of Science ®Google Scholar
• Ulcerative Colitis: Developing Drugs for Treatment. Draft Guidance for Industry. (CBER) CfBEaR. editor. 2022.
   Google Scholar
• Guideline on the development of new medicinal products for the treatment of ulcerative colitis. (CHMP) CfMPfHU. editor. 2018.
   Google Scholar
• Biomarkers consortium - mucosal healing in UC: definition, treatment target and clinical endpoints foundation for the national institutes of Health. 2021. [cited 2022 Dec 5]. Available from: https://fnih.org/our-programs/biomarkers-consortium/programs/mucosal-healing
   Google Scholar
• Atreya R, Peyrin-Biroulet L, Klymenko A, et al. Cobitolimod for moderate-to-severe, left-sided ulcerative colitis (CONDUCT): a phase 2b randomised, double-blind, placebo-controlled, dose-ranging induction trial. Lancet Gastroenterol Hepatol. 2020 Dec;5(12):1063–1075.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet (London, England). 2023 Apr 8;401(10383):1159–1171. doi: 10.1016/S0140-6736(23)00061-2
   PubMed Web of Science ®Google Scholar
• Feagan BG, Danese S, Loftus EV Jr., et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet (London, England). 2021 Jun 19;397(10292):2372–2384. doi: 10.1016/S0140-6736(21)00666-8
   PubMed Web of Science ®Google Scholar
• Peyrin-Biroulet L, Allegretti JR, Rubin DT, et al. Guselkumab in patients with moderately to severely active ulcerative colitis: QUASAR phase 2b induction study. Gastroenterology. 2023 Sep 1;165(6):1443–1457.10.1053/j.gastro.2023.08.038
   PubMed Web of Science ®Google Scholar
• An induction study of Mirikizumab in participants with moderately to severely active ulcerative colitis (LUCENT 1). Available from: https://classic.clinicaltrials.gov/show/NCT03518086
   Google Scholar
• A maintenance study of Mirikizumab in participants with moderately to severely active ulcerative colitis. Available from: https://classic.clinicaltrials.gov/show/NCT03524092
   Google Scholar
• Sandborn WJ, Feagan BG, D’Haens G, et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021 Sep 30;385(14):1280–1291. doi: 10.1056/NEJMoa2033617
   PubMed Web of Science ®Google Scholar
• Risankizumab (SKYRIZI®) Met primary and key secondary endpoints in 52-week phase 3 maintenance study in ulcerative colitis patients [Internet]. 2023 Jun 15. Available from: https://news.abbvie.com/2023-06-15-Risankizumab-SKYRIZI-R-Met-Primary-and-Key-Secondary-Endpoints-in-52-Week-Phase-3-Maintenance-Study-in-Ulcerative-Colitis-Patients
   Google Scholar
• Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet (London, England). 2022 Jun 4;399(10341):2113–2128. doi: 10.1016/S0140-6736(22)00581-5
   PubMed Web of Science ®Google Scholar
• Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2019 Sep 26;381(13):1201–1214. doi: 10.1056/NEJMoa1900750
   PubMed Web of Science ®Google Scholar
• A study to evaluate the safety and efficacy of ustekinumab induction and maintenance therapy in participants with moderately to severely active ulcerative colitis. Available from: https://classic.clinicaltrials.gov/show/NCT02407236
   Google Scholar
• D’Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2023 Jun 29;388(26):2444–2455. doi: 10.1056/NEJMoa2207940
   PubMed Web of Science ®Google Scholar
• Pai RK, Hartman DJ, Rivers CR, et al. Complete resolution of mucosal neutrophils associates with improved long-term clinical outcomes of patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2510–2517.e5
   PubMed Web of Science ®Google Scholar
• Kobayashi T, Motoya S, Nakamura S, et al. Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2021 Jun;6(6):429–437.
   PubMed Web of Science ®Google Scholar
• Jangi S, Yoon H, Dulai PS, et al. Predictors and outcomes of histological remission in ulcerative colitis treated to endoscopic healing. Aliment Pharmacol Ther. 2020 Sep;52(6):1008–1016.
   PubMed Web of Science ®Google Scholar
• Christensen B, Hanauer SB, Erlich J, et al. Histologic normalization occurs in ulcerative colitis and is associated with improved clinical outcomes. Clin Gastroenterol Hepatol. 2017 Oct;15(10):1557–1564.e1.
   PubMed Web of Science ®Google Scholar
• Shaffer SR, Erondu AI, Traboulsi C, et al. Achieving histologic normalization in ulcerative colitis is associated with a reduced risk of subsequent dysplasia. Inflamm Bowel Dis. 2022 Mar 30;28(4):553–559.10.1093/ibd/izab130
   PubMed Web of Science ®Google Scholar
• Magro F, Pai RK, Kobayashi T, et al. Resolving histologic inflammation in ulcerative colitis with mirikizumab in the LUCENT induction and maintenance trial programs. J Crohn’s & Colitis. 2023 Apr 14;17(9):1457–1470. doi: 10.1093/ecco-jcc/jjad050
   PubMed Web of Science ®Google Scholar
• Verstockt B, Pouillon L, Ballaux F, et al. Patient-reported outcomes and disability are associated with histological disease activity in patients with ulcerative colitis: results from the APOLLO study. J Crohn’s & Colitis. 2023 Jul 5;17(7):1046–1054. doi: 10.1093/ecco-jcc/jjad015
   PubMed Web of Science ®Google Scholar
• Narula N, Wong ECL, Colombel JF, et al. Early change in epithelial neutrophilic infiltrate predicts long-term response to biologics in ulcerative colitis. Clin Gastroenterol Hepatol. 2022 May;20(5):1095–1104.e9.
   PubMed Web of Science ®Google Scholar
• Determination of the optimal treatment target in ulcerative colitis. Available from: https://ClinicalTrials.gov/show/NCT04259138
   Google Scholar
• Honig G, Heller C, Hurtado-Lorenzo A. Defining the path forward for biomarkers to address unmet needs in inflammatory bowel diseases. Inflamm Bowel Dis. 2020 Sep 18;26(10):1451–1462.
   PubMed Web of Science ®Google Scholar
• D’Inca R, Sturniolo G. Biomarkers in IBD: what to utilize for the diagnosis? Diagnostics (Basel). 2023 Sep 13;13(18). doi: 10.3390/diagnostics13182931
   PubMedGoogle Scholar
• Jukic A, Bakiri L, Wagner EF, et al. Calprotectin: from biomarker to biological function. Gut. 2021 Oct;70(10):1978–1988.
   PubMed Web of Science ®Google Scholar
• D’Amico F, Bonovas S, Danese S, et al. Review article: faecal calprotectin and histologic remission in ulcerative colitis. Aliment Pharmacol Ther. 2020 Apr;51(7):689–698.
   PubMed Web of Science ®Google Scholar
• Dulai PS, Peyrin-Biroulet L, Danese S, et al. Approaches to integrating biomarkers into clinical trials and care pathways as targets for the treatment of inflammatory bowel diseases. Gastroenterology. 2019 Oct;157(4):1032–1043 e1.
   PubMed Web of Science ®Google Scholar
• Guirgis M, Wendt E, Wang LM, et al. Beyond histological remission: Intramucosal Calprotectin as a potential predictor of outcomes in ulcerative colitis. J Crohn’s & Colitis. 2017 Apr 1;11(4):460–467.
   PubMed Web of Science ®Google Scholar
• Römkens TEH, Kranenburg P, Tilburg AV, et al. Assessment of histological remission in ulcerative colitis: discrepancies between daily practice and expert opinion. J Crohn’s & Colitis. 2018 Mar 28;12(4):425–431. doi: 10.1093/ecco-jcc/jjx165
   PubMed Web of Science ®Google Scholar
• Maeda Y, Kudo SE, Mori Y, et al. Fully automated diagnostic system with artificial intelligence using endocytoscopy to identify the presence of histologic inflammation associated with ulcerative colitis (with video). Gastrointest Endosc. 2019 Feb;89(2):408–415.
   PubMed Web of Science ®Google Scholar
• Nakase H, Hirano T, Wagatsuma K, et al. Artificial intelligence-assisted endoscopy changes the definition of mucosal healing in ulcerative colitis. Dig Endosc. 2021 Sep;33(6):903–911.
   PubMed Web of Science ®Google Scholar
• Ahmad HA, East JE, Panaccione R, et al. Artificial intelligence in inflammatory bowel disease endoscopy: implications for clinical trials. J Crohn’s & Colitis. 2023 Aug 21;17(8):1342–1353. doi: 10.1093/ecco-jcc/jjad029
   PubMed Web of Science ®Google Scholar
• Byrne MF, Panaccione R, East JE, et al. Application of deep learning models to improve ulcerative colitis endoscopic disease activity scoring under multiple scoring systems. J Crohn’s & Colitis. 2023 Apr 19;17(4):463–471. doi: 10.1093/ecco-jcc/jjac152
   PubMedGoogle Scholar
• Bossuyt P, Nakase H, Vermeire S, et al. Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density. Gut. 2020 Oct;69(10):1778–1786.
   PubMed Web of Science ®Google Scholar
• Iacucci M, Smith SCL, Bazarova A, et al. An international multicenter real-life prospective study of electronic chromoendoscopy score PICaSSO in ulcerative colitis. Gastroenterology. 2021 Apr;160(5):1558–1569.e8.
   PubMed Web of Science ®Google Scholar
• Gui X, Bazarova A, Del Amor R, et al. PICaSSO histologic remission index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system. Gut. 2022 May;71(5):889–898.
   PubMed Web of Science ®Google Scholar
• Iacucci M, Parigi TL, Del Amor R, et al. Artificial intelligence enabled histological prediction of remission or activity and clinical outcomes in ulcerative colitis. Gastroen. 2023 Jun;164(7): 1180–1188. doi: 10.1053/j.gastro.2023.02.031
   PubMed Web of Science ®Google Scholar
• Karstensen JG, Săftoiu A, Brynskov J, et al. Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy (with videos). Gastrointest Endosc. 2016 Aug;84(2):279–286.e1.
   PubMed Web of Science ®Google Scholar
• Rahmi G, Coron E, Perrod G, et al. Probe-based confocal laser endomicroscopy for in vivo assessment of histological healing in ulcerative colitis: development and validation of the ENHANCE index. J Crohn’s & Colitis. 2021 Jun 22;15(6):994–999. doi: 10.1093/ecco-jcc/jjaa255
   PubMed Web of Science ®Google Scholar
• Katsanos KH, Papadakis KA. Inflammatory bowel disease: updates on molecular targets for biologics. Gut Liver. 2017 Jul 15;11(4):455–463.
   PubMed Web of Science ®Google Scholar
• Neurath MF, Leppkes M. Resolution of ulcerative colitis. Semin Immunopathol. 2019 Nov;41(6):747–756. doi: 10.1007/s00281-019-00751-6
   PubMed Web of Science ®Google Scholar