Assessing trial eligibility and real-world response to vedolizumab and ustekinumab in patients with ulcerative colitis

BACKGROUND: large randomized controlled trials (RCTs) with strict criteria for patient enrollment. As newer IBD medications are approved, ongoing assessment is necessary to determine whether RCT eligibility criteria are too restrictive or adequately reflect real-world practice. Here, we investigate the trial-eligibility and clinical outcomes of patients with ulcerative colitis (UC) started on vedolizumab (VDZ) and ustekinumab (UST) therapy. METHODS: This single-center retrospective cohort study at a large academic IBD referral center included patients with UC who received a new prescription for UST or VDZ between January 2020 and June 2023. The primary outcome assessed whether patients met trial eligibility using the inclusion and exclusion criteria from the UNIFI and GEMINI-1 RCTs. We also assessed treatment failure between the trial-eligible and ineligible groups. RESULTS: = 83 receiving UST) were trial-eligible. The most common reasons for ineligibility were prior biologics and inadequate wash-out periods, the use of topical therapy, medical comorbidities and ongoing treatment with high doses of prednisone. Treatment failure was numerically higher in trial-ineligible compared to trial-eligible patients, though this difference was not statistically significant. CONCLUSION: Most patients initiated on UST or VDZ would not have qualified for inclusion in their respective RCTs, largely due to current treatments. Revising trial eligibility criteria may be warranted to improve external validity and enable recruitment of a more diverse study population representative of real-world patients.