Lead Investigator: Neeraj Narula, Hamilton Health Sciences
Title of Proposal Research: Patient Reported Symptoms as Predictors of Endoscopic Improvement in Ulcerative Colitis
Vivli Data Request: 7158
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.
An important goal of treatment in ulcerative colitis is endoscopic improvement (EI). EI is a term used to describe improvement in the endoscopic appearance of the colon mucosa and is defined as Mayo endoscopic score of 0 or 1 in the VARISTY study (clinicaltrials.gov identifier: NCT02497469). In clinical trials, patients often undergo endoscopic assessments after a period of time since starting therapy (e.g. 8-14 weeks) and after one year to assess if EI was achieved.
In addition to endoscopy, patient-reported symptoms (rectal bleeding and stool frequency) also reflect disease activity but are not necessarily specific to UC. Patients with UC may also have co-existing gastrointestinal conditions which may impact rectal bleeding and stool frequency. Conversely, some patients may be asymptomatic but have active endoscopic disease. Thus, patient-reported symptoms poorly correlate with the degree of inflammation as assessed by endoscopy.
The primary objective of this study is to investigate the relationship between patient-reported symptoms after completing the induction phase of treatment (week 6) and EI at one year. One year will be used as the endpoint as it was the primary endpoint used in the VARSITY study. The scientific community and patients with UC may benefit from the knowledge generated from this study. Specifically, the results of this study will provide evidence in support of strategies (e.g. reliance on symptoms, endoscopy/objective markers, or a combination of both) to assist in treatment decision-making.
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 including disease duration, treatment allocation, and concomitant corticosteroid use. To account for multiple hypotheses testing, the statistical significance level will be set at 0.025.
Sensitivity analyses will be conducted using the defined independent variables at week 14. Stratified analyses (endoscopic disease severity, disease location, treatment allocation, and prior exposure to a TNF inhibitor) will also be conducted.
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 Chu Lee Wong, Badar Hasan, Parambir S. Dulai, John K. Marshall, Walter Reinisch & Neeraj Narula. (2022). End of induction patient reported outcomes predict clinical remission and endoscopic improvement with vedolizumab and adalimumab in ulcerative colitis. Scandinavian Journal of Gastroenterology. DOI: 10.1080/00365521.2022.2105169