DOI: 10.25934/00006686
title: Extended Validation of an Ulcerative Colitis Vedolizumab Decision Support Tool

description: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by bloody diarrhea and periods of relapse and remission, with an estimated prevalance in North America of 37.5 to 238 per 100,000 (1). Achievement of endoscopic remission and histologic remission are associated with improved long-term outcomes including preventing of hospitalization, surgery, and colon cancer.(2) The achievement of endoscopic and histologic remission is best done with biologics such as Vedolizumab and Adalimumab. These biologics have relative strengths and weaknesses, and indirect comparative effectiveness data would suggest similaritly in treatment response between these 2 agents.(3) A recent head-to-head clinical trial for Vedolizumab versus Adalimumab in UC has demonstrated that Vedolizumab results in higher rates of clinical and endoscopic remission.(4) This might suggest that Vedolizumab is superior to Adalimumab and should therefore always be used first line prior to this therapy, however, sub-group analyses within this trial have observed that this superiority is not universal across all patient populations.(4) There is currently no guidance for societies on how to consider these data and best personalize this decision within the context of this head-to-head to trial.(5)

We have previously built a clinical decision support tool using the phase 3 clinical trial program for Vedolizumab in UC.(6) We observed this tool to be accurate for identifying Vedolizumab treated UC patients who would achieve clinical and endoscopic remission within the clinical trial programs. During the external, routine practice validation, we were able to confirm the diagnostic performance of this tool and its ability to identify UC patients most likely to respond to Vedolizumab therapy. We were also able to further extend the value of this tool by demonstrating that this tool did not predict response to anti-tumor necrosis factor (TNF) therapy and that this tool was able to identify UC patients who were more likely to respond to Vedolizumab as compared to anti-TNF therapy.(6) This tool therefore helps to personalize the decision in routine practice for patients who are often not included in the phase 3 and 4 clinical trial programs,(7) and brings forward personalization of this decision within the context of the recently completed head-to-head trial for Vedolizumab. Some limitations remain, however, which include: the lack of blinded centralized endoscopy scoring in the routine practice validation cohort, the lack of balancing between Vedolizumab and anti-TNF treated patients for unmeasured confounders, and the lack of assessment for histologic outcomes which are now known to be of clinical significance are increasingly being incorporated as a key end-point in clinical trials and clinical practice.(8)

In the current proposal we aim to specifically address these gaps through a post-hoc analysis of the VARSITY clinical trial program. The clinical trial design of this study allows for balancing of measured and unmeasured confounders between Vedolizumab and Adalimumab treated UC patients, and the centralized blinded assessment of endoscopy and histology allows for further extension of our decision support tool to outcomes of growing importance.