Impact of Prior Biologic Mechanism of Action on Anti‐ TNF Effectiveness in Inflammatory Bowel Disease: An ENEIDA Registry Study

BACKGROUND: The expanding use of targeted therapies in inflammatory bowel disease has made treatment sequencing increasingly relevant, yet evidence on anti-TNF effectiveness after prior biologics with different mechanisms of action (MOA) remains limited. Our objective is to evaluate the durability of anti-TNF treatment in this scenario. METHODS: Multicentre study based on data from the ENEIDA registry. Patients who received second-line anti-TNF therapy after a first biologic with a different MOA for active luminal disease were identified. Using propensity score matching, each case was matched with three controls from two cohorts: patients treated with second-line anti-TNF after another anti-TNF and patients receiving first-line anti-TNF therapy. Treatment durability and short- and long-term clinical effectiveness were assessed. RESULTS: Sixty-six Crohn's disease patients and 117 UC patients receiving anti-TNF after other MOA were included. In CD, second-line anti-TNF therapy after a different MOA (62% ustekinumab) was associated with a higher risk of treatment discontinuation compared with first-line anti-TNF therapy (HR 1.55; 95% CI, 1.05-2.30), without significant differences in short- or long-term clinical effectiveness. In UC, anti-TNF therapy after a different MOA (90% vedolizumab) was associated with lower treatment durability compared with first-line anti-TNF therapy (HR 1.69; 95% CI, 1.31-2.19) and with anti-TNF after another anti-TNF agent (HR 1.91; 95% CI, 1.48-2.48), its remission rates significantly lower at both short- and long-term follow-up (p < 0.001). CONCLUSIONS: Anti-TNF therapy used after a different MOA is associated with reduced effectiveness and durability compared with its use as first-line therapy or after another anti-TNF agent, especially in UC.