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Abstract BACKGROUND Pediatric Crohn’s Disease (CD) patients who achieve deep remission, defined as both clinical remission and endoscopic healing (EH), have fewer disease complications. The gold standard for assessing EH is ileocolonoscopy (IC), which can be invasive and costly. EH can be calculated using multiple scoring systems including the common Simple Endoscopic Score for Crohn’s Disease (SES-CD), the Simplified Endoscopic Mucosal Assessment for Crohn’s Disease (SEMA-CD) which streamlines scoring, or the Modified Multiplier SES-CD (MM-SES-CD), which uses weights for each SES-CD parameter based on prognostic value. Here, we sought to identify biomarkers associated with EH. As a secondary endpoint, we sought to validate the SEMA-CD and MM-SES-CD in our population and use these scoring methods to further evaluate biomarkers. METHODS A multicenter, cross-sectional study enrolled CD patients scheduled for an IC. Inclusion was age 2-21 years receiving either infliximab (IFX) or adalimumab (ADA) for >6 months. Blood samples were collected to measure c-reactive protein (CRP), serum albumin (ALB), neutrophil CD64 activity ratio (nCD64), soluble CD64 (sCD64), and drug concentrations. Fecal calprotectin (fCal) and fecal lactoferrin (fLacto) were measured from stool prior to the IC. The SES-CD and SEMA-CD were calculated from video recordings by two separate reviewers, when possible. MM-SES-CD was tabulated from the SES-CD scores. Agreement between endoscopic scores was calculated using intraclass correlation coefficient (ICC). Pair-wise comparisons were made using parametric or non-parametric tests as appropriate. RESULTS Of the 91 enrolled patients, 87 had a complete IC. EH defined by SES-CD< 3, SEMA-CD< 1 and MM-SEC-CD< 14 was achieved in 55.1%, 45.3%, and 67.8% of patients, respectively. The ICC for the SES-CD was 0.91 (95% CI: 0.84-0.95), 0.87 (0.77-0.93) for SEMA-CD, and MM-SES-CD 0.87 (0.77-0.93). There was excellent correlation between the SES-CD and SEMA-CD (Spearman r=0.89, p< 0.001) and MM-SES-CD (Spearman r=0.99, p< 0.001) and between the SEMA-CD and MM-SES-CD (Spearman r=0.89, p< 0.001). We found that lower levels of fCal, fLacto, CRP, novel biomarkers sCD64 and nCD64, and an elevated ALB level were significantly associated with EH for all scoring modalities. Patients without EH had more rapid IFX clearance using SES-CD only. Cut points (Youden Index) were identified for each biomarker and demonstrated notable similarity across scoring methods (Table1). CONCLUSIONS We identified remarkable similarities in EH blood and stool biomarkers using different endoscopic scoring modalities, highlighting the reliability of these markers to detect inflammation. However, our results also indicate that some important EH markers, like drug clearance, may be missed using a singular endoscopic scoring system. Table 1. Biomarkers of Endoscopic Healing by Endoscopic Scoring System
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