Comparative Real‐World Effectiveness of Anti‐ TNF , Ustekinumab and Vedolizumab in Crohn's Disease Over 24 Months: A Pooled Analysis From the Prospective UMBRELLA ‐ IBD Registry in Germany

BACKGROUND: Real-world evidence is needed to understand the comparative effectiveness of biologics in Crohn's disease (CD) under routine-care conditions. We conducted a pooled analysis of individual patient data from prospective German CD registries (BioCrohn, RUN-CD, VEDO-IBD) in the UMBRELLA-IBD data warehouse. METHODS: We included 1567 adults with CD who initiated anti-TNF therapy (adalimumab or infliximab), ustekinumab or vedolizumab. The main outcome was clinical remission (CR) at 24 months (HBI ≤ 4). Additional outcomes included HBI, EQ-VAS and treatment persistence over time. Between-group comparisons used propensity-score-based inverse probability of treatment weighting. RESULTS: After weighting, CR following induction was observed in a slightly higher proportion of patients initiating anti-TNF therapy (74.5%) than ustekinumab (69.4%) or vedolizumab (65.3%) (p = 0.035). Clinical response was 77.9%, 73.5% and 67.8%, respectively (p = 0.015). At 24 months, CR rates were similar in magnitude (anti-TNF, 53.4%; ustekinumab, 63.5%; vedolizumab, 58.7%) but were higher with ustekinumab than anti-TNF (p = 0.004). Over 24 months, treatment persistence differed (log-rank p < 0.001) and was highest for adalimumab (81.4%), lowest for infliximab (66.6%), and intermediate for ustekinumab (78.6%) and vedolizumab (76.9%). HBI decreased and remained low, and EQ-VAS improved, with no relevant between-group differences. CONCLUSION: Overall effectiveness in CD was high, with only small differences between biologic therapies. At the end of induction, CR was slightly higher with anti-TNF therapy than with vedolizumab, whereas at 24 months it was slightly higher with ustekinumab than with anti-TNF. Marked differences in treatment persistence among the evaluated biologics suggest that persistence as an endpoint is not fully explained by CR alone.