Lead Investigator: Neeraj Narula, Hamilton Health Sciences
Title of Proposal Research: Extended Validation of an Ulcerative Colitis Vedolizumab Decision Support Tool for Outcome Prediction with Tofacitinib
Vivli Data Request: 8294
Funding Source: None
Potential Conflicts of Interest: 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:
Vedolizumab is biologic approved for moderate to severe ulcerative colitis, which specifically targets the gut to help improve inflammation. Biologics are drugs that are made of animal and/or human cells, viruses, and proteins. Several other biologics are available with various modes of action and the optimal treatment for some patients remain unclear. The majority of guidance surrounding choice of therapy encourages clinicians to consider all available therapies given currently available evidence as opposed to explicitly outlining which therapies are better suited for specific patient populations. In the absence of explicit guidelines, I previously developed and validated a clinical decision support tool specifically for vedolizumab that has demonstrated the ability to identify ulcerative colitis patients who may derive the greatest benefit with vedolizumab. More importantly, I have demonstrated this tool can predict response specifically to vedolizumab rather than anti-TNF therapy, which are drugs that reduce inflammation in conditions such as ulcerative colitis. However, further validation is needed to compare the prognostic value of this tool for vedolizumab compared to therapies with other modes of action in a post-hoc analysis using robust data from randomized clinical trials. The primary aim of this study is to further validate the ability of the clinical decision support tool to identify ulcerative colitis patients suited for vedolizumab treatment compared to tofacitinib, which is as small molecule drug. These drugs have very low molecular weight and can be taken orally. This validation exercise may benefit ulcerative colitis patients as it can provide greater confidence in the use and uptake of the clinical decision support tool in clinical settings for vedolizumab.
Statistical Analysis Plan:
Baseline characteristics will be summarized using descriptive statistics and outcomes among patients stratified by the groupings of the clinical decision support tool scoring system.1 Categorical variables will be presented as proportions or percentages. Continuous variables will be reported as means and associated standard deviations or medians and associated interquartile ranges.
The clinical decision support tool score for all patients will be calculated using data at baseline. This is a numeric score calculated as follows:
• Absence of prior anti-TNF exposure = + 3 points
• Disease duration of 2 years or more = + 3 points
• Moderate (Mayo 2) baseline endoscopic activity = + 2 points
• Baseline albumin = +0.65 points per 1 g/L
Subsequently, the area under the curve (AUC) of the receiver operative characteristic (ROC) will be determined for the score from the clinical decision support tool for predicting one-year outcomes. Patients will then be grouped into low, intermediate, or high probability of response based on cut-offs that have been established previously. The rates of outcomes between sub-groups by the probability of response (low – 26 points or less, intermediate – 27 to 32 points, and high – 33 points or more, probability) will be compared to determine if differences between groups exist. Confidence intervals will be calculated at the 95% interval, and p-value threshold of 0.05 will be used. Data will be analyzed using Stata.
I hypothesize that the performance of the score will be lower than the performance from the model originally derived and validated given that the clinical decision support tool specifically predicts response to vedolizumab in UC. This would provide evidence in favour of the clinical decision support tool for predicting who patients who would benefit the most from vedolizumab.
Requested Studies:
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis
Data Contributor: Pfizer
Study ID: NCT01465763
Sponsor ID: A3921094
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis.
Data Contributor: Pfizer
Study ID: NCT01458951
Sponsor ID: A3921095
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As A Maintenance Therapy In Subjects With Ulcerative Colitis
Data Contributor: Pfizer
Study ID: NCT01458574
Sponsor ID: A3921096
Public Disclosures:
Dulai, P.S., Wong, E.C., Johnson, B., Cox, K., Theriault, N., Stefan, M., Eldasher, L.M. and Narula, N., 2023. Su1712 AN ULCERATIVE COLITIS DECISION SUPPORT TOOL PREDICTS DRUG SPECIFIC ENDOSCOPIC REMISSION AND IMPROVES PROVIDER MASTERY IN TREATMENT SELECTION. Gastroenterology, 164(6), pp.S-647.