S1963 Among Patients With Crohn's Disease Who Have Failed Anti-TNF Therapy, What Are the Efficacy and Safety Outcomes of Switching to Ustekinumab Compared to Vedolizumab?

Introduction: Anti-tumor necrosis factor (anti-TNF) agents serve as first-line biologics for Crohn’s disease (CD). Up to 30% of patients lose response or develop intolerance, requiring other treatments. Ustekinumab (UST) and vedolizumab (VDZ) have been used as second-line biologics for anti-TNF refractory CD. This systematic review analyzes 37 studies to compare outcomes of switching to UST vs VDZ after anti-TNF failure in CD patients. Methods: The search was conducted on Ovid MEDLINE, Ovid Embase, and Cochrane Central databases to find studies comparing UST and VDZ in anti-TNF refractory CD patients. Thirty-7 studies encompassing 5,651 patients (61.4% on UST and 38.6% on VDZ) were included. Data on clinical response, remission, steroid-free remission, endoscopic and radiologic outcomes, treatment persistence, adverse events, and hospitalization were extracted. Both short-term (induction phase, typically 14 weeks) and long-term outcomes (up to 12 months or more) were analyzed. Adjusted hazard ratios, odds ratios, and survival analyses were incorporated to compare outcomes. Meta-analytic approaches were limited by study heterogeneity; thus, a narrative synthesis was performed. Results: UST showed higher clinical and steroid-free remission rates compared to VDZ, both at induction (e.g., clinical remission 33% UST vs 26% VDZ at week 14) and during maintenance (up to 1 year). Treatment persistence was consistently higher with UST, with reported 12-month retention rates reaching 84% vs approximately 62% for VDZ. Endoscopic and radiologic response data favored UST in some cohorts. Safety profiles were comparable between treatments, with no significant differences in adverse events or infection-related hospitalizations. Notably, patients switching outside the anti-TNF class (to UST or VDZ) experienced better outcomes than those switching within the anti-TNF class. Some heterogeneity in results was attributable to geographic variations in drug approval and patient selection. Conclusion: This review suggests that UST may offer greater efficacy and treatment persistence than VDZ for anti-TNF refractory CD patients. These findings support preferential use of UST in this setting, although individual patient factors and local regulatory approvals should guide therapy choice. The current evidence is observational, emphasizing the need for randomized controlled trials directly comparing these agents.