Lead Investigator: Neeraj Narula, Hamilton Health Sciences
Title of Proposal Research: Combined Histologic and Endoscopic Endpoints in Ulcerative Colitis
Vivli Data Request: 7772
Funding Source: None
Potential Conflicts of Interest: Neeraj Narula holds a McMaster University Department of Medicine Internal Career Award. Neeraj Narula has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, Lupin and Ferring. None of the listed conflicts of interest are aware of or are involved in this research.
Summary of the Proposed Research:
Ulcerative colitis (UC) is an inflammatory bowel disease that affects the colon and rectum. UC causes inflammation in the colon and ulcers. Resolution of symptoms is an important goal of treatment in UC, which is defined as clinical remission (CR). CR is assessed in clinical trials by using the partial Mayo score, with a score of 0 indicating CR (i.e. complete resolution of rectal bleeding and abdominal pain). In addition to CR, endoscopic disease is important to assess as patients who achieve endoscopic improvement, often defined as Mayo endoscopic subscore < 2, have a greater likelihood of favourable outcomes. UC patients who undergo endoscopy usually also have biopsies of the colon taken, which can be used to assess for histologic disease activity. Histologic assessment of the colon can provide important information regarding the degree of inflammation in the colon. The Geboes score is a histologic scoring tool frequently used to assess histologic disease in UC, with histologic improvement defined as Geboes highest grade < 3.2. Clinical trials of UC have adopted histologic endpoints as part of co-primary or secondary endpoints, such as histo-endoscopic mucosal improvement (HEMI), which is a combination of endoscopic improvement and histologic improvement.
Despite the growing importance of endoscopic and histologic outcomes in UC, it is unclear how combined definitions of endoscopic and histologic endpoints such as HEMI compare to stand alone definitions of endoscopic improvement and histologic improvement. The relevance of these endpoints compared to CR and corticosteroid-free CR also requires further investigation. Further, markers of clinical disease severity, as measured by the partial Mayo score, and markers of inflammatory burden need to be better understood.
Statistical Analysis Plan:
For all analyses, descriptive statistics will be provided. Continuous variables will be presented as means and standard deviation or as medians and inter-quartile ranges. Dichotomous variables will be presented as proportions or percentages. Unadjusted and adjusted odds ratios for achieving the outcomes of interest will be calculated. Multiple logistic regression analyses of outcomes will be performed adjusting for baseline variables determined on univariate analyses. Variables with a p < 0.10 on univariate will be considered for inclusion in the multivariate model. Spearman’s correlation coefficient will be reported for analyses comparing histologic indices. Sensitivity and stratified analyses will be performed as detailed in the protocol.
A Randomized, Double-Blind, Double-Dummy, Multicenter, Active-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab IV Compared to Adalimumab SC in Subjects With Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT02497469
Sponsor ID: MLN0002-3026
Emily C L Wong, BHSc, Parambir S Dulai, MD, Badar Hasan, MD, John K Marshall, MD, MSc, FRCPC, Walter Reinisch, MD, PhD, Neeraj Narula, MD, MPH, FRCPC. Combined Histologic and Endoscopic Endpoints at Post-induction Lack Additional Prognostic Value Compared to Endoscopic Improvement Alone in Ulcerative Colitis: A Post-hoc Analysis of the VARSITY study. Journal of Crohn’s and Colitis, 2023;, jjad033. doi: 10.1093/ecco-jcc/jjad033