Diagnostic accuracy of fecal calprotectin testing for assessing endoscopic activity of disease in symptomatic patients with inflammatory bowel disease: a systematic review and meta-analysis

Abstract

BACKGROUND. Fecal calprotectin (FC) testing has been proposed as a replacement test for ileocolonoscopy in symptomatic patients with inflammatory bowel disease (IBD) to assess for endoscopic activity. OBJECTIVES. Primary: to characterize the diagnostic accuracy of FC testing for assessing endoscopic activity in symptomatic IBD patients. Secondary: to explore how diagnostic accuracy varies according to clinical, technical, and methodological characteristics. METHODS. We searched MEDLINE and Embase to February 8, 2024. We included single-gate diagnostic studies on symptomatic patients with IBD, adult or pediatric. Index test: laboratory-conducted quantitative immunochemical assays for FC, with positivity thresholds 50-300 μg/g. Stool samples were produced within seven days before the ileocolonoscopy but not after initiating bowel preparation. Target condition: Endoscopically active disease in the colon or terminal ileum. Reference standard: white-light-imaging ileocolonoscopy Two authors independently assessed study eligibility, extracted study data, and assessed methodological quality (with QUADAS-2) and certainty of evidence (GRADE approach). We intended to conduct the meta-analysis with the bivariate random effects model. We intended to investigate heterogeneity with predetermined subgroup analyses, sensitivity analyses and meta-regression analyses. The protocol was registered in PROSPERO (ID: CRD42023420120). RESULTS. We screened 7,398 abstracts and assessed 598 full-text publications. No study met the criteria for inclusion. By a post hoc protocol deviation, we contacted the authors of two marginally ineligible studies, acquired unpublished data and included the studies in an expansive sensitivity analysis (<75% symptomatic participants). The certainty of evidence was very low due to serious (or very serious) risk of bias, serious imprecision, and serious indirectness. There were concerns about selective reporting bias. Methodological innovations: (a) enhanced QUADAS-2 instrument capturing the direction of the effect of the risk of bias; (b) the concept of expansive sensitivity analyses. CONCLUSIONS. Despite the common use of FC testing in symptomatic patients with IBD, no study has evaluated its diagnostic accuracy.