Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Feb 15, 2016; 7(1): 1-16
Published online Feb 15, 2016. doi: 10.4291/wjgp.v7.i1.1
Mucosal healing in inflammatory bowel disease: Maintain or de-escalate therapy
Marcello Cintolo, Giuseppe Costantino, Socrate Pallio, Walter Fries
Marcello Cintolo, Giuseppe Costantino, Walter Fries, Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
Socrate Pallio, Digestive Endoscopy Unit, Department of Human Pathology, University of Messina, 98125 Messina, Italy
Author contributions: Cintolo M and Fries W drafted and wrote the manuscript; Costantino G and Pallio S critically reviewed the manuscript; all authors approved the final version of the article.
Conflict-of-interest statement: Marcello Cintolo, Giuseppe Costantino and Socrate Pallio have no conflict of interests to declare. Walter Fries, MSD, AbbVie, Mundipharma advisory board; Zambon, Mundipharma: speaker fees; MSD unrestricted research grant.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Walter Fries, MD, Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, 98125 Messina, Italy. fwalter@unime.it
Telephone: +39-090-2212380 Fax: +39-090-2213538
Received: July 29, 2015
Peer-review started: August 24, 2015
First decision: October 13, 2015
Revised: November 16, 2015
Accepted: December 7, 2015
Article in press: December 8, 2015
Published online: February 15, 2016

In the past decade, thanks to the introduction of biologic therapies, a new therapeutic goal, mucosal healing (MH), has been introduced. MH is the expression of an arrest of disease progression, resulting in minor hospitalizations, surgeries, and prolonged clinical remission. MH may be achieved with several therapeutic strategies reaching success rates up to 80% for both, ulcerative colitis (UC) and Crohn’s disease (CD). Various scoring systems for UC and for the transmural CD, have been proposed to standardize the definition of MH. Several attempts have been undertaken to de-escalate therapy once MH is achieved, thus, reducing the risk of adverse events. In this review, we analysed the available studies regarding the achievement of MH and the subsequent treatment de-escalation according to disease type and administered therapy, together with non-invasive markers proposed as predictors for relapse. The available data are not encouraging since de-escalation after the achievement of MH is followed by a high number of clinical relapses reaching up to 50% within one year. Unclear is also another question, in case of combination therapies, which drug is more appropriate to stop, in order to guarantee a durable remission. Predictors of unfavourable outcome such as disease extension, perianal disease, or early onset disease appear to be inadequate to foresee behaviour of disease. Further studies are warranted to investigate the role of histologic healing for the further course of disease.

Keywords: De-escalation, Mucosal healing, Biological therapy, Deep remission, Discontinuation, Ulcerative colitis, Crohn’s disease, Immunosuppressors

Core tip: Mucosal healing is achieved in a discrete number of patients with immunomodulators, biologics or combined therapies. Attempts to de-escalate therapy, thus permitting a drug holiday, are disappointing. Clinical predictors to identify patients at risk for early relapse after drug withdrawal are still insufficient. Further investigations are needed to prospectively evaluate the validity of histologic healing and to validate an appropriate scoring system for histology in ulcerative colitis and in Crohn’s disease.