Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease: A Systematic Review and Practical Guide

Abstract

Background: In asymptomatic patients with inflammatory bowel disease (IBD), "monitoring" involves repeated testing aimed at early recognition of disease exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin (FC) measurements to predict IBD relapses by a systematic literature review.

Methods: An electronic search was performed in Medline, Embase, and Cochrane from inception to April 2016. Inclusion criteria were prospective studies that followed patients with IBD in remission at baseline and had at least 2 consecutive FC measurements with a test interval of 2 weeks to 6 months. Methodological assessment was based on the second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist.

Results: A total of 1719 articles were identified; 193 were retrieved for full text review. Six studies met eligibility for inclusion. The time interval between FC tests varied between 1 and 3 months. Asymptomatic patients with IBD who had repeated FC measurements above the study's cutoff level had a 53% to 83% probability of developing disease relapse within the next 2 to 3 months. Patients with repeated normal FC values had a 67% to 94% probability to remain in remission in the next 2 to 3 months. The ideal FC cutoff for monitoring could not be identified because of the limited number studies meeting inclusion criteria and heterogeneity between selected studies.

Conclusions: Two consecutively elevated FC values are highly associated with disease relapse, indicating a consideration to proactively optimize IBD therapy plans. More prospective data are necessary to assess whether FC monitoring improves health outcomes.

FIGURE 1. Conceptual model of FC monitoring in IBD patients

Figure adapted from ‘Do Not Read Single Calprotectin Measurements in Isolation When Monitoring Your Patients with Inflammatory Bowel Disease’ by P.F. van Rheenen, Inflammatory bowel disease, 20:1416–7. Copyright 2014 by the Wolters Kluwer Health, Inc. Adapted with permission.

FIGURE 2. Flow diagram systematic literature search

Reasons for exclusion at last stage (*): - Serial measurements of FC not reported (n=69) - Congress abstract (n=53) - Patients had active disease at baseline (n=29) - FC test interval out of desired range (<2 weeks or >6 months) (n=14) - Narrative review, Editorial, Letter to editor, or Comment (n=7). - FC test results within 6 months before relapse not reported (n=7) - FC cut-point not reported (n=3) - Language other than English (n=3) - Less than 10 participants (n=2)