Five-Year Real-World Hard Outcomes of Vedolizumab in Inflammatory Bowel Disease: The IG-IBD LONG-LIVE Study

Long-term real-world data on vedolizumab outcomes remain limited: the LONG-LIVE study evaluates 5-year effectiveness and safety in a large Italian cohort. This is a long-term extension of the multicenter LIVE study involving patients with Crohn’s disease (CD) and ulcerative colitis (UC). The primary outcome was the cumulative probability of major adverse clinical outcomes (the composite of IBD-related surgeries, non-surgical hospitalizations, and serious adverse events). Secondary outcomes included cumulative incidences of IBD-related surgery and non-surgical hospitalization, vedolizumab persistence, rates of death, cancer and adverse events of special interest (AESIs), and longitudinal response group transitions; outcomes in elderly patients (≥ 65 years) were compared to non-elderly using inverse probability weighting (IPW). Overall, 782 patients were included (50.4% CD; 49.6% UC; 76.3% anti-tumor necrosis factor (TNF)-experienced; 4324.1 patient-years of follow-up). The 5-year probability of major adverse clinical outcomes was 29.4% (no difference between CD and UC). In CD, penetrating behavior (aHR 1.77) predicted higher risk of the primary endpoint, while colonic location was protective (aHR 0.51). In UC, the primary endpoint was predicted by elderly age (aHR 1.99) and comorbidity burden (aHR 1.27). Five-year cumulative incidences were 23.4% for surgery and 14.3% for non-surgical hospitalization. Patients with CD had higher hospitalization risk than patients with UC (sHR 1.80). Mortality, neoplasm diagnosis, and AESIs occurred at rates of 3.93, 3.93, and 6.27 per 1000 patient-years. Five-year drug persistence was 38.7%. Achieving deep remission within 24 months mediated the relationship between initial clinical response and sustained deep remission at last follow-up. After IPW, elderly patients had a higher risk of major adverse clinical outcomes and non-surgical hospitalization; AESI and cancer rates did not differ. Approximately one in three patients experienced a major adverse clinical outcome over 5 years, driven primarily by disease-related complications rather than adverse events, with a consistent safety profile across age groups. Vedolizumab is a gut-selective biologic therapy approved for Crohn's disease (CD) and ulcerative colitis (UC). While its short-term effectiveness is well established, data on what happens to patients beyond 2 years of treatment remain limited. In this study, we followed 782 patients for up to 7 years across 47 Italian centers to track hard clinical outcomes: surgery, hospitalization, serious adverse events, and death. About one in three patients experienced a major adverse clinical outcome over 5 years—a composite endpoint that includes IBD-related surgeries, non-surgical hospitalizations, and serious adverse events—with no meaningful difference between CD and UC. Surgery occurred in approximately one in five patients, and non-surgical hospitalizations were more frequent in CD. Serious adverse events, including deaths, cancers, and infections, remained uncommon throughout follow-up. Patients who responded early to treatment were more likely to achieve deep remission within 2 years, which was in turn associated with deep remission at last follow-up. Elderly patients faced higher risks of hospitalization and major adverse clinical outcomes, but not of cancer or serious adverse events, suggesting that vedolizumab can be used across different age groups without a disproportionate increase in safety risk.