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. 2024 Nov;12(9):1266-1279.
doi: 10.1002/ueg2.12671. Epub 2024 Oct 5.

Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective

Tommaso Lorenzo Parigi  1   2 , Virginia Solitano  1   3 , Alessandro Armuzzi  4   5 , Manuel Barreiro de Acosta  6 , Jake Begun  7 , Shomron Ben-Horin  8 , Luc Biedermann  9 , Jean-Frederic Colombel  10 , Axel Dignass  11 , Mathurin Fumery  12 , Subrata Ghosh  13 , Taku Kobayashi  14 , Edouard Louis  15 , Fernando Magro  16 , Remo Panaccione  17 , Astrid Rausch  18 , Walter Reinisch  19 , Christian Selinger  20 , Vipul Jairath  3   21 , Silvio Danese  1   2 , Laurent Peyrin-Biroulet  22
Affiliations

Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective

Tommaso Lorenzo Parigi et al. United European Gastroenterol J. 2024 Nov.

Abstract

Background: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD).

Methods: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD.

Results: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint.

Conclusions: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment.

Keywords: Crohn's disease; IBD; clinical trials; deep remission; endoscopy; histologic healing; histological healing; neutrophils; pathology; ulcerative colitis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Reporting of mucosal healing as an endpoint in randomized controlled trials of new agents for ulcerative colitis. EMA, European medicines agency; FDA, food and drugs administration; MES, mayo endoscopic subscore; MH, mucosal healing.
FIGURE 2
FIGURE 2
Inclusion of histological assessment in the definition of mucosal healing in randomized controlled trials of ulcerative colitis. MH, mucosal healing.
FIGURE 3
FIGURE 3
Reporting of mucosal healing as endpoint in Randomized Controlled Trials of Crohn's disease. CDEIS, Crohn's disease endoscopic index of severity; EMA, European medicines agency; FDA, food and drugs administration; MH, mucosal healing; SES‐CD, simplified endoscopic score for Crohn's disease.
See this image and copyright information in PMC

References

    1. Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne JF, et al. Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn’s disease. A prospective multicentre study of 121 cases. The Groupe d’Etudes Thérapeutiques des Affections Inflammatoires Digestives. Gut. 1994;35(2):231–235. 10.1136/gut.35.2.231 - DOI - PMC - PubMed
    1. Peyrin‐Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat‐to‐target. Am J Gastroenterol. 2015;110(9):1324–1338. 10.1038/ajg.2015.233 - DOI - PubMed
    1. Ma C, Hanzel J, Panaccione R, Sandborn WJ, D’Haens GR, Ahuja V, 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;163(4):950–964. 10.1053/j.gastro.2022.06.068 - DOI - PubMed
    1. Ordás I, Rimola J, Rodríguez S, Paredes JM, Martínez‐Pérez MJ, Blanc E, et al. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn’s disease. Gastroenterology. 2014;146(2):374–382.e1. 10.1053/j.gastro.2013.10.055 - DOI - PubMed
    1. Allocca M, Fiorino G, Bonovas S, Furfaro F, Gilardi D, Argollo M, et al. Accuracy of humanitas ultrasound criteria in assessing disease activity and severity in ulcerative colitis: a prospective study. J Crohn’s Colitis. 2018;12(12):1385–1391. 10.1093/ecco-jcc/jjy107 - DOI - PMC - PubMed

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