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Intestinal Barrier Healing Assessed by Confocal Endomicroscopy Predicts Long-term Outcomes in Patients With Inflammatory Bowel Disease

Francis A. Farraye, MD, MSc, FASGE reviewing Rath T, et al. Gastroenterology 2022 Oct 21.

Treatment beyond clinical remission is recommended by the International Organization for the Study of Inflammatory Bowel Disease in its publication of the Selective Therapeutic Targets in Inflammatory Bowel Disease-II (STRIDE-II) initiative (Gastroenterology. 2021;160:1570-1583) for patients with Crohn's disease (CD) and ulcerative colitis (UC). In particular, endoscopic healing is a long-term target. Histologic remission was not defined as a treatment target in either CD or UC but could be used as an adjunct to endoscopic remission in UC. No comment was made regarding the assessment of barrier function in this document. A multicenter study aimed to determine whether barrier healing assessed by confocal endomicroscopy is useful in predicting long-term outcomes in patients with inflammatory bowel disease (IBD) in clinical remission.

In this prospective study, after screening 296 patients with IBD, 181 patients (100 CD, 81 UC) in clinical remission were included in the final analysis. During mean follow-up periods of 35 (CD) and 25 (UC) months, 73% of patients with CD and 69% with UC had at least one major adverse outcome (MAO), defined as disease flares, IBD-related hospitalization or surgery, or initiation or dose escalation of steroids or advanced therapies. 

Patients in endoscopic remission versus those with endoscopically active disease were less likely to have an MAO. Histologic remission predicted a lower likelihood of experiencing an MAO for patients with UC but not CD. Finally, barrier healing shown on endomicroscopy was better than endoscopic and histologic remission for predicting MAO-free disease course in both UC and CD. There was no correlation between barrier healing assessed by endomicroscopy and serum levels of albumin, C-reactive protein, and zonulin.


Although additional larger studies are needed, these important and exciting data suggest that intestinal barrier healing is more sensitive and specific than endoscopic and histologic remission for predicting lack of clinically important major adverse outcomes in patients with IBD. Confocal endomicroscopy requires fluorescein injection, is expensive, and availability is limited to tertiary IBD centers. Although advances in artificial intelligence platforms might increase the use of this endoscopic technology, efforts to identify nonendoscopic surrogates of barrier healing are needed to facilitate the assessment of intestinal permeability for clinicians treating patients with IBD.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

Francis A. Farraye, MD, MSc, FASGE

Bio and Disclosures


Rath T, Atreya R, Bodenschatz J, et al. Intestinal barrier healing is superior to endoscopic and histologic remission for predicting major adverse outcomes in IBD: the prospective ERIca trial. Gastroenterology 2022 Oct 21. (Epub ahead of print) (