Sa1194 Prospective, Multicenter Capsule Endoscopy Study of Small Bowel Crohn's Disease Patients in Clinical Remission: Long-Term Follow-Up and Correlation With Faecal Lactoferrin and Calprotectin Levels

Background: Histologic assessment is an evolving outcome measure in ulcerative colitis (UC). Many histological indices, including the Geboes score (GS; Figure 1 top panel) and Modified Riley Score (MRS; Figure 1 bottom panel) have been used to grade disease activity and served as endpoints for clinical trials. The operating properties of these indices, including agreement have not been fully evaluated. We assessed interand intra-rater agreement of central readers for histopathological evaluation of UC disease activity.Methods: Five central readers individually evaluated 50 slides of colonic biopsies taken from patients with UC on three separate occasions at least two weeks apart using the GS, MRS and a global rating of severity based on a 100 mm visual analogue scale (VAS). Interand intra-rater agreement was measured using intraclass correlation coefficients (ICC) for each grading system and for components of acute and chronic inflammation. Results: Intra-rater ICCs (95% confidence intervals) for the total GS, MRS and VAS scores were 0.83 (0.78, 0.87), 0.72 (0.65, 0.79) and 0.79 (0.74, 0.85), respectively. Corresponding inter-rater agreement ICCs were 0.57 (0.45, 0.68), 0.49 (0.38, 0.61) and 0.61 (0.51, 0.72) (Table 1). The correlation between each central reader's VAS with GS and MRS descriptors were 0.60 (0.44, 0.76) and 0.63 (0.47, 0.77), respectively. The items with lowest ICC (highest disagreement) were granuloma (0.01), patchiness (0.20), lamina propria fibrosis (0.21), lamina propria eosinophilia (0.26), crypt abscesses (0.32), crypt destruction (0.34), surface epithelium integrity (0.35), and lamina propria neutrophils (0.37). Conclusion: There is "substantial" to "almost perfect" intra-rater agreement among histopathologists in the assessment of disease activity in UC. Inter-rater agreement was less satisfactory. The results indicate that a central reader is highly reliable for the assessment of UC histologic disease. However, differences in interpretations of the scores among readers requires further study and standardization in order to determine the optimal instrument for use in UC clinical trials. A Delphi process has been initiated to further characterize the most important sources of disagreement. Table 1. Interand Intra-rater Agreement for Index Components