A Composite Morphometric Duodenal Biopsy Mucosal Scale for Celiac Disease Encompassing both Morphology and Inflammation

Abstract

Background & Aims<br/>Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease (CeD). While the field of CeD has advanced, there remains no broadly accepted measure of mucosal injury. We assessed whether a composite Vh:Cd and IEL scale (named VCIEL) can improve accuracy and statistical precision for assessing histology, compared to individual measures.<br/><br/>Methods<br/>The formulation of the VCIEL composite histologic scale was based on combining the Vh:Cd and IEL measurements for individual patients with equal weighting, by converting each scale to a fraction of their standard deviation and summing the results. The VCIEL formula was applied to several clinical trials and the results for Vh:Cd and IELwere compared to those for VCIEL with regards to clinical significance (effect size) and statistical significance.<br/><br/>Results<br/>For the ALV003-1021 trial, we observed an effect size and p-value (ANCOVA) of 1.37, 0.038 for ΔVh:Cd, 1.17, 0.005 for ΔIEL and 1.86, 0.004 for ΔVCIEL. For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding results were 0.76, 0.057 for ΔVh:Cd, 0.98, 0.018 for ΔIEL and 1.14, 0.007 for ΔVCIEL. Similar improvements with the use of VCIEL over individual Vh:Cd and IEL measures were observed for other studies, including a non-therapeutic gluten challenge study.<br/><br/>Conclusions<br/>The composite VCIEL scale combining Vh:Cd and IEL values appears to improve accuracy and statistical precision compared to either component alone.<br/>