Lead Investigator: Neeraj Narula, McMaster University
Title of Proposal Research: Impact of Ulcer Size and Extent of Inflammation On Ability To Achieve Endoscopic Healing In Crohn’s Disease: An EXTEND Post-Hoc Analysis
Vivli Data Request: 5567
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Crohn’s disease is an inflammatory condition of the bowel which affects 1 in 250 patients in North America. Endoscopic healing of the bowel has become a goal of treatment for patients with Crohn’s disease. Clinical trials conducted in Crohn’s disease for new therapies need to demonstrate the ability to heal the mucosa before receiving regulatory authority approvals for use. However, nothing is known about the impact of lesion size and distribution on the ability to achieve endoscopic healing. Arbitrary scoring systems like the Simplified Endoscopic Score for Crohn’s disease (SES-CD) or the Crohn’s disease Endoscopic Index Score (CDEIS) are used to grade inflammation, but the scores appear to be arbitrary, as it has been shown patients with higher scores are just as likely to heal as those with lower scores (Narula et al. Am J Gastroenterol 2020). This study looks to validate the pre-existing work by myself and look at the EXTEND database and determine whether patients who have more extensive inflammation at baseline and larger ulcer sizes are less likely to achieve endoscopic healing. Univariate analyses will be conducted to look for baseline variables which have a significant relationship with the outcome of interest – endoscopic healing at week 54. This will include evaluation of specific endoscopic features – for example, large ulcers vs. not large ulcers in the ileum.
Statistical Analysis Plan:
The EXTEND study is being requested as it is one of very few studies that had two scoring systems used to score endoscopic inflammation (SES-CD and CDEIS). This will allow for me to look at features that are recorded in both scoring systems (like ulcer size and depth) to determine the relevance of these factors on likelihood of achieving endoscopic healing.
Continuous variables will be presented as means (and standard deviations [SD] or as medians and interquartile ranges [IQR]) if the distribution is skewed, and categorical or binary variables will be presented as proportions or percentages. Descriptive statistics will be used to summarize baseline demographics, disease characteristics and outcome parameters of Crohn’s disease patients with baseline mucosal lesions at screening colonoscopy.
Univariate analyses will be conducted to look for baseline variables which have a significant relationship with the outcome of interest – endoscopic healing at week 54. This will include evaluation of specific endoscopic features – for example, large ulcers vs. not large ulcers in the ileum. This will also include other baseline demographic factors. Known baseline disease factors significantly associated with the outcome of interest (i.e. endoscopic healing) found to be significant on univariate analyses, will be included within a multivariate logistic regression analysis to help adjust for potential confounding factors and reduce bias. The logistic regression model which includes variable of interest (i.e. ulcer size for example), and the other potential confounding factors found significant on univariate analyses, as described above
Patients with missing data will be omitted from the multivariate analysis.
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab Endoscopy Trial to Evaluate the Effects on Mucosal Healing in Subjects With Crohn’s Disease Involving the Colon
Study ID: NCT00348283
Sponsor ID: M05-769
Narula N, Wong ECL, Colombel J, et alPredicting endoscopic remission in Crohn’s disease by the modified multiplier SES-CD (MM-SES-CD) Gut Published Online First: 25 March 2021. doi: 10.1136/gutjnl-2020-323799