Background and aims: Endoscopic assessment of mucosal appearance by independent central reading has become the standard method to assess Crohn's disease activity in clinical trials. The performance characteristics of various endoscopy reading models have yet to be systematically evaluated.
Methods: This substudy included patients with Crohn's disease in the exploratory induction cohort of the BERGAMOT trial (NCT02394028) randomly assigned to etrolizumab or placebo. Endoscopies conducted at baseline and week 14 were independently scored using the Simple Endoscopic Score for Crohn's Disease (SES-CD) by a local reader (LR) and 2 central readers (CRs). Five endoscopy reading models were compared: single LR, single CR, average of 2 CRs, and 2 models incorporating the LR and 1 or 2 CRs depending on alignment between the LR and the CR, defined according to a sliding scale applied to a range of scores.
Results: Five hundred thirty-five videos were scored. Models involving 2 readers demonstrated lower placebo rates (3.4%) than the single LR (11.9%) and the single CR (6.8%) models. Treatment effect size based on endoscopic improvement (≥50% reduction in SES-CD from baseline) was highest with the 2 models incorporating the LR and 1 or 2 CRs (Δ = 16.2%). Further, in the etrolizumab arm, models with 2 readers demonstrated the lowest variability for the SES-CD.
Conclusions: Central endoscopy reading models in Crohn's disease have an impact on placebo response rates and effect size. Incorporating the LR appears to be important because models using both CRs and LRs resulted in the greatest treatment effect size for endoscopic improvement with etrolizumab, lower placebo rates, and reduced variability.
Copyright © 2021. Published by Elsevier Inc.