Evaluation of Blood and Stool Biomarkers Across Three Fecal Calprotectin Platforms and Combination Testing for Predicting Endoscopic and Histologic Outcomes in Inflammatory Bowel Disease

Abstract Background Non-invasive biomarkers are increasingly used to monitor inflammatory bowel disease (IBD), but differences among fecal calprotectin assays and the incremental value of combining fecal biomarkers remain uncertain. We aimed to compare the correlation and diagnostic performance of fecal calprotectin (FC) measured using three analytical platforms, fecal immunochemical test (FIT), and serum C-reactive protein (CRP) for predicting endoscopic and histologic outcomes in IBD. Methods We conducted a single-center observational study of adults with IBD who underwent ileocolonoscopy at Siriraj Hospital, Thailand. FC was measured using latex agglutination, fluoroenzyme immunoassay, and chemiluminescent immunoassay platforms. Quantitative FIT and serum CRP were also assessed. Endoscopic activity was evaluated using the Mayo Endoscopic Score or Simple Endoscopic Score for Crohn’s Disease, and histologic activity using the Nancy Histological Index. Correlations were assessed using Spearman correlation coefficients, and diagnostic performance using receiver operating characteristic analysis and predefined cutoffs. A linear mixed model compared fecal calprotectin levels across platforms. Results Among 133 patients, 74 (55.6%) had ulcerative colitis (UC) and 59 (44.4%) had Crohn’s disease (CD); 123 (92.5%) were in clinical remission. FC showed excellent correlation across the three platforms (Spearman r = 0.95–0.96, all P < 0.001), despite significantly different absolute concentrations. For predicting mucosal healing, FC demonstrated good and comparable discrimination across platforms (AUROC 0.82–0.83), outperforming CRP (0.62). FIT showed high sensitivity (90.7%) but limited specificity (43.1%) at the predefined cutoff, whereas FC provided a more balanced diagnostic profile. In clinically quiescent UC combining FIT with FC increased specificity but did not improve sensitivity. In CD, combination testing provided no additional benefit over FC alone. Conclusions FC demonstrated the most consistent overall diagnostic performance for assessing objective disease activity in IBD, although absolute values differed substantially between assay platforms. FIT may be useful as a sensitive screening biomarker, whereas FC is more suitable for confirming mucosal healing. Combining the two tests provides limited additional value in clinically quiescent IBD. Trial registration: ClinicalTrials.gov, NCT06623383, registered on September 30, 2024