Optimal Range of Fecal Calprotectin for Predicting Mucosal Healing in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Abstract

<b><i>Objective:</i></b> Fecal calprotectin (FC) is a promising marker for assessment of inflammatory bowel disease (IBD) activity. However, the utility of FC for predicting mucosal healing (MH) of IBD patients has yet to be clearly demonstrated. The objective of our study was to perform a meta-analysis evaluating the diagnostic accuracy of FC in predicting MH of IBD patients. <b><i>Methods:</i></b> We systematically searched the databases for studies from inception to April 2020 that evaluated MH in IBD. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. <b><i>Results:</i></b> Sixteen studies comprising 1,682 ulcerative colitis (UC) patients and 4 studies comprising 221 Crohn’s disease (CD) patients were included. The best performance of FC for predicting MH in UC was at cut-off range of 60–75 μg/g with area under the curve (AUC) of 0.88 and pooled sensitivity and specificity of 0.87 and 0.79, respectively. The pooled sensitivity and specificity values of cutoff range 180–250 μg/g for predicting MH in CD were 0.67 and 0.76, respectively. The AUC of 0.79 also revealed improved discrimination for identifying MH in CD with FC concentration. <b><i>Conclusion:</i></b> Our meta-analysis has found that FC is a simple, reliable noninvasive marker for predicting MH in IBD patients. FC cutoff range 60–75 μg/g appears to have the best overall accuracy in UC patients.

Achievement of Clinical, Endoscopic, and Histological Outcomes in Patients with Ulcerative Colitis Treated with Etrasimod, and Association with Faecal Calprotectin and C-reactive Protein: Results From the Phase 2 OASIS Trial

“…However, the κ coefficients for clinical remission, endoscopic improvement, histologic remission, and EIHR were only 0.4560, 0.4404, 0.3273, and 0.3584, respectively; thus, the FCP cutoff concentration of 250 µg/g had only fair to moderate accuracy in classifying individual clinical, endoscopic, and histological outcomes. This FCP cutoff value is higher than that observed in some other studies; 22 however, many of those studies used different definitions of EIHR. Furthermore, we believe that specific ‘thresholds’ must be interpreted with caution and both CRP and FCP results should not be labelled as ‘positive’ or ‘negative’.…”

Is There any Association between Fecal Calprotectin Levels and Cystic Fibrosis?

“…Calprotectin is a complex of two light (S100A8) and heavy (S100A9) heterodimers and exists in the cytoplasm of neutrophils and the membrane of monocytes. It is released in the serum and body fluids following the activation of neutrophils and monocytes and can be considered an inflammationrelated biomarker in inflammatory diseases, such as arthritis, periodontitis, CF, sclerosing cholangitis, and IBD, including Crohn's disease and ulcerative colitis (8,9,10). Calprotectin stimulates the inflammatory response by increasing the production of special inflammatory chemokines and the expression of adhesion molecules.…”

Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease

“…Another meta-analysis that included 1682 and 221 patients with UC and CD, respectively, investigated the optimal FC range for predicting MH[ 37 ]. The optimal performance in UC was at a cutoff range of 60-75 μg/g, with high sensitivity (0.87, 95%CI: 0.80-0.91) and specificity (0.81, 95%CI: 0.76-0.85).…”