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.