Published online Nov 7, 2017. doi: 10.3748/wjg.v23.i41.7387
Peer-review started: August 19, 2017
First decision: August 30, 2017
Revised: September 18, 2017
Accepted: September 29, 2017
Article in press: September 28, 2017
Published online: November 7, 2017
Currently, there is increased need for the discovery of simple to perform, non-invasive biomarkers with high correlation to intestinal inflammatory activity in patients with inflammatory bowel disease (IBD). Fecal calprotectin (FC) measurement has shown promise as a candidate marker for this purpose.
Although the value of measuring FC as an indicator for active inflammation is indisputable, the correlation between FC values and future flare of disease activity has not been fully established. Furthermore, uncertainty still exists regarding the optimal cut-off values of FC for this indication and applicability of its measurement in diverse patient groups.
Our principal aim was to study the clinical significance of measuring FC in IBD patients in clinical remission, both as a biomarker for patients stratification according to their risk for relapse, as well as a surrogate marker of endoscopic mucosal healing.
We retrospectively analyzed the electronic medical records of all patients with IBD, with a regular follow up at our department and a FC measurement in a 3-year study period. We specifically focused on patients in stable clinical remission and a medium-term follow-up (at least 6-mo). We then compared two groups of patients: those who remained in remission and those who relapsed (according to pre-defined criteria) during the 6-mo follow-up. A secondary aim of our study was to examine whether the measured FC value could predict the presence or absence of mucosal healing (defined as an endoscopic Mayo Score of 0 for UC and absence of significant mucosal lesions in the colon and terminal ileum for CD, respectively). For all study participants, demographic, epidemiologic and clinical data were retrieved from the patient files and entered in an SPSS database.
The main findings of our analysis are as follows: First, patients who relapsed within 6-mo from FC measurement had significantly higher baseline FC concentrations than those who remained in remission. Second, patients with mucosal abnormalities in endoscopy (i.e. absence of mucosal healing) had significantly higher FC values as compared to patients that demonstrated endoscopic mucosal healing. Third, we were able to define cut-off values for FC concentrations with high sensitivity and specificity for predicting clinical relapse or endoscopical activity in patients with IBD in clinical remission. Fourth, combining FC with CRP measurements further increases the predictive value for short-term clinical flare. Finally, cut-offs may be significantly lower in patients with post-surgical recurrence of CD in comparison to surgery-free patients.
Our findings clearly indicate that short-term clinical relapse can be predicted with high accuracy by measuring FC concentration in patients with IBD. Consequently, serial FC measurements may prove to be a very useful tool to monitor subclinical inflammatory activity in IBD patients who are in clinical remission. Furthermore, our results show that a high FC value is a surrogate marker of endoscopically active disease. Given the high importance that mucosal healing has gained in recent years for determining disease outcomes in IBD, FC measurements may become a valuable tool for the selection of those patients who need to have an endoscopy while in clinical remission. Subsequently, treatment modifications may be preemptively implemented in such cases, in order to avoid clinical recurrence of symptoms and the systemic consequences of persisting inflammatory activity.