Lead Investigator: Neeraj Narula, Hamilton Health Sciences
Title of Proposal Research: Early vs. Delayed Response to Vedolizumab in Ulcerative Colitis
Vivli Data Request: 7225
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 a type of inflammatory bowel disease that causes inflammation and ulcers to form in the colon and rectum. There are several ways to assess disease severity, which include patient-reported symptoms (rectal bleeding and stool frequency), physician’s global assessment, and endoscopy. The Mayo score is comprised of all four of these components and each is scored from a scale of 0 to 3 (total score ranging from 0 to 12), with higher scores indicating more severe symptoms/disease activity. The Mayo endoscopic score is used at the time of endoscopy to assess the appearance of the colon mucosa. The partial Mayo score excludes the endoscopic score.
Improvement in symptoms is an important goal of treatment for UC patients, which is often defined as clinical remission (CR). As an outcome in clinical trials, CR is often defined using stringent criterion of partial Mayo score of 0 (i.e. complete resolution of UC-related symptoms). However, early response (e.g. by week four to six) is often defined using more lenient criterion of partial Mayo score ≤ 1.
With various treatment options available for UC, there is a need to distinguish relative efficacy and speed of onset. While rapid speed of onset is important, recent studies suggest that patients starting on therapies such as vedolizumab may experience a delayed response. Therefore, patients may be monitored for several months on therapy and which can prevent early switching to other biologics. However, this practice of hopeful waiting may result in patients remaining on ineffective therapy. It is unclear whether patients with a delayed response to therapy have as robust and durable a response as those who attained response earlier.
Statistical Analysis Plan:
Descriptive statistics will be provided for all analyses. Continuous variables will be presented as means [and standard deviations (SD)] or as medians [and inter-quartile ranges (IQR)], and dichotomous variables presented as proportions or percentages. Unadjusted odds ratios and adjusted odds ratios for achieving the outcomes of interest will be calculated. Multivariate logistic regression models will evaluate the relationship between the independent variables (as described above) and achievement of the outcomes of interest. Adjustments for known confounders of symptoms will be performed. Multiple logistic regression analysis of week 52 clinical and endoscopic outcomes will be performed adjusting for baseline variables determined on univariate analyses. Backward selection will be used for inclusion of variables in the multivariate models, with the threshold for exclusion set at p ≥ 0.15. All baseline variables with p-values < 0.05 on univariate analysis will be considered for inclusion within the multivariate model. Sensitivity and stratified analyses will be performed as detailed above.
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
Narula, Neeraj MD, MPH, FRCPC; Wong, Emily C.L. BHSc; Marshall, John K. MD, MSc, FRCPC; Jairath, Vipul MD, PhD; Dulai, Parambir S. MD; Reinisch, Walter MD, PhD. Long-term Outcomes of Early Versus Delayed Responders to Vedolizumab and Adalimumab: A Post-hoc Analysis of VARSITY. The American Journal of Gastroenterology: September 1, 2022 – Volume – Issue – 10.14309/ajg.0000000000001987 doi: 10.14309/ajg.0000000000001987