Vedolizumab vs TNF Antagonists and Long-Term Outcomes in Ulcerative Colitis.

Importance: Tumor necrosis factor (TNF) antagonists and vedolizumab are the most commonly used advanced therapies for management of moderate-to-severe ulcerative colitis (UC). There are limited data evaluating long-term outcomes with a TNF antagonist-first vs vedolizumab-first treatment strategy. Objective: To compare long-term clinical outcomes among biologic-naive patients with UC initiating infliximab or adalimumab vs vedolizumab as first-line advanced therapy. Design, Setting, and Participants: This Swedish nationwide population-based cohort study used linked health registers. Biologic-naive patients with UC who initiated infliximab, adalimumab, or vedolizumab between January 1, 2015, and June 30, 2021, were included and followed up until June 30, 2023, for a median of 4.3 to 5.4 years. Data analysis was conducted from April to September 2025. Exposures: Initiation of a TNF antagonist (ie, infliximab or adalimumab) or vedolizumab as first-line advanced therapy. Main Outcomes and Measures: The primary outcome was the incidence rate of all-cause hospitalizations (including recurrent events). Secondary outcomes included incidence rates of colectomy, corticosteroid dispensations, advanced therapy switching, and proportion of quarters spent in corticosteroid-free disease stability (defined as no oral corticosteroid dispensation, no initiation of a new advanced therapy or immunomodulator, and no hospitalization or colectomy within a 3-month period). Groups were balanced using inverse probability of treatment weighting (IPTW) accounting for disease characteristics, health care utilization, comorbidities, and medication use. Results: Overall, 3263 patients (1393 infliximab, 1583 adalimumab, and 287 vedolizumab initiators) were included. After IPTW, there were with 1385 infliximab initiators (mean [SD] age, 38 [18] years; 43% female) compared with 320 vedolizumab initiators (mean [SD] age, 36 [19] years; 35% female) and 1575 adalimumab initiators (mean [SD] age, 41 [16] years; 48% female) compared with 318 vedolizumab initiators (mean [SD] age, 38 [19] years; 43% female). All-cause hospitalization did not differ significantly between infliximab and vedolizumab initiators (incidence rate ratio [IRR], 1.14 [95% CI, 0.91-1.43]); however, infliximab initiators spent a significantly lower proportion of time in corticosteroid-free disease stability over 5 years than vedolizumab initiators (60% vs 67% of quarters; risk ratio [RR], 0.88 [95% CI, 0.82-0.94]). Similarly, all-cause hospitalization did not differ significantly between adalimumab and vedolizumab initiators (IRR, 1.08 [95% CI, 0.86-1.35]), although adalimumab initiators had greater therapy switching (IRR, 1.21 [95% CI, 1.02-1.43]) and less time in corticosteroid-free stability (67% vs 70% of quarters; RR, 0.92 [95% CI, 0.87-0.98]) than vedolizumab initiators. Results were broadly consistent in 1:1 propensity score-matched sensitivity analyses. Conclusions and Relevance: In this cohort study of biologic-naive patients with UC initiating advanced therapy, the burden of hospitalization did not differ significantly between patients receiving vedolizumab and those receiving a TNF agonist; however, a vedolizumab-first strategy was associated with a greater proportion of time spent in corticosteroid-free disease stability over 5 years than a TNF antagonist-first strategy. These findings may inform first-line treatment selection in UC.