Letter: mucosal healing is associated with improved long‐term outcomes in Crohn's disease

Abstract

We read with interest the article by Shah et al. comparing long-term outcomes in patients with active Crohn's disease who achieve mucosal healing compared with those who do not.1 The authors found that achieving mucosal healing at first endoscopic assessment is associated with increased rates of long-term clinical remission and maintenance of mucosal healing in active Crohn's disease, and may therefore be a reasonable therapeutic target. Shah et al.'s meta-analysis gives rise to the question as to whether either mucosal healing or clinical remission should be the main treatment goal in Crohn's disease. Precise definitions of mucosal healing in Crohn's disease need to be resolved and proper comparative effectiveness trials need to be performed to confirm that this endpoint is clinically meaningful. In some studies, mucosal healing was defined as a Mayo Score of 0 or 1.2, 3 A score of ‘1’ (erythema, diminished vascular markings) might plausibly describe patients with a broad spectrum of symptoms. Therefore, despite meeting the study's definition of mucosal healing, there remains a significant proportion of patients with some degree of persistent endoscopic inflammation. To add to the confusion, the authors could not conclude this result, because it used an entirely different definition of mucosal healing. At the same time, mucosal healing has been refined to a microscopic level, with some studies showing a significant association between the degree of histological inflammation and an increased risk of flaring over the course of Crohn's disease. We agree that mucosal healing is an important endpoint that should be studied in clinical trials. However, some issues still limit the use of mucosal healing as a therapeutic target of Crohn's disease in clinical practice. Firstly, a validated standard system for grading histologic activity does not exist. Validation is a prerequisite to standardize reporting and grading. Secondly, the exact definition of histologic healing, as well as their impact on clinical outcome of Crohn's disease, has yet to be clarified. Thirdly, the optimal staining method for grading the severity of inflammation is still unclear. Haematoxylin–eosin is the most frequently used staining, but more expensive methods, such as immunohistochemistry, may provide information. Fourth, the timing and site of the biopsy to show normalized histology have to be clarified. Fifth, mucosal healing is not a reliable target in clinical practice – it is not an easy goal to reach, and inflammation may persist despite clinical–endoscopic remission. Our study reported that mucosal healing did not predict sustained clinical remission in patients with inflammatory bowel disease when infliximab therapies had been stopped.4 In summary, before considering mucosal healing as a reliable target for the treatment of Crohn's disease, large prospective studies will have to address the key issues we have discussed. Declaration of personal and funding interests: None.