Mucosal Healing
The assessment and monitoring of disease activity is indispensable for the optimal therapeutic management of IBD patients. Our therapeutic decisions are based on its evaluation, and analysis of disease activity is essential for endpoints in clinical trials. The mere improvement of clinical symptoms alone is not regarded as sufficient anymore, but must be ideally accompanied by mucosal restitution. This process has been termed mucosal healing, and it was proposed that it might lead to the modification of the natural disease course by slowing down or even preventing the progression of disease [
5,
6,
7]. Mucosal healing is predominantly defined by endoscopic assessment of intestinal inflammation and is mostly referred to as the absence of mucosal ulcerations in Crohn's disease [
8]. In ulcerative colitis, there is more disparity in the published definitions; however, an international consensus defined it as the absence of friability, blood, erosions, and ulcers of the gut mucosa (fig.
1) [
9]. In order to evaluate the presence or absence of mucosal healing on endoscopy, various endoscopic scoring systems have been developed. The most frequently used endoscopic activity indices in Crohn's disease are the Crohn's Disease Endoscopic Index of Severity (CDEIS), the Simple Endoscopic Score for Crohn's Disease, and the Rutgeerts score. In ulcerative colitis, the Mayo Clinic endoscopic subscore and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) are those most widely used [
5,
6]. These indices allow us to determine improvements of endoscopic lesions, even when the rather rigid endpoint of mucosal healing and thereby the total disappearance of all mucosal ulcerations is not met. Other measures of assessing the disease activity are represented by the biomarkers C-reactive protein and fecal calprotectin. They are currently not regarded as targets for treatment but are helpful indices in monitoring the patient. Histopathology is another measure of inflammation but can also not be defined as a therapeutic target at the moment [
10]. However, several recent studies suggest that histologic healing of intestinal inflammation is a better predictor of long-term patient outcomes in ulcerative colitis as compared to mucosal healing on endoscopy.
Fig. 1
Endoscopic images of a Crohn's disease patient a with mucosal ulcerations in the terminal ileum and b subsequent mucosal healing as defined by absence of ulcers and CDEIS scoring. Endoscopic images of an ulcerative colitis patient c with inflammation in the sigmoid and d subsequent mucosal healing as defined by absence of friability, blood, erosions, and ulcers as well as reduction of the endoscopic Mayo score.
Mucosal healing can only represent an indispensable treatment goal if it serves as a validated surrogate marker for effective control of the disease and subsequently for the positive modulation of the disease course. Until now, there have been no long-term interventional studies comparing the outcome of clinical versus mucosal healing-based approaches for the disease course of IBD patients. There is no prospective evidence that mucosal healing, for example, predicts a reduced need for surgeries as an endpoint for disease modification. In contrast, there are substantial indirect indications from large case series that mucosal healing is associated with better patient-related outcome matters such as reduced risk of relapse, better steroid tapering, fewer hospitalization and surgeries, lower rate of colectomies, and improved ability to work [
5,
6]. These are important correlative findings, as the selected endpoints define improved quality of life for the IBD patient. Nevertheless, some aspects have to be taken into account before defining mucosal healing as an obtainable treatment goal in all IBD patients.
In this regard, one has to consider that in some patients, especially those with long-standing Crohn's disease, mucosal healing may not always reflect healing of all layers of the tissue, as endoscopy only addresses mucosal rather than transmural healing. Furthermore, one has to consider safety aspects when trying to achieve mucosal healing by intensifying the ongoing therapy, thereby increasing the risk of potentially severe side-effects. Additionally, cost aspects associated with the adaption of therapies to attain mucosal healing cannot be disregarded. Altogether, definite prospective proof that an intensification of the therapy to achieve mucosal healing is able to modulate the natural disease course is still missing. This aspect should be demonstrated in prospective trials investigating the course of disease, as it would only then be justified to escalate therapy in a patient with clinical remission to achieve mucosal healing. It should therefore be carefully evaluated in which individual circumstances mucosal healing may be proposed as the target for therapeutic interventions.
