Real-world comparison of effectiveness between ustekinumab and a second-line anti-TNF agent in patients with symptomatic stricturing Crohn's disease failing to respond to a first-line anti-TNF agent: the USTEKNOSIS study.

Background: Anti-tumor necrosis factor (TNF) agents are now accepted as the first-line medical treatment for stricturing Crohn's disease (CD). However, data are lacking about the effectiveness of advanced therapies after anti-TNF failure. Objectives: To compare the effectiveness of ustekinumab and a second-line anti-TNF agent after failing to respond to a first-line anti-TNF for a symptomatic stricturing CD. Design: Multicenter retrospective study. Methods: We included consecutive adult patients with CD treated with ustekinumab or anti-TNF for symptomatic stricture (confirmed on imaging or endoscopy) after prior failure of one anti-TNF for the current stricture. Short-term endpoints were symptomatic remission (composite endpoint) at 6 months, defined as no abdominal pain, no vomiting, no food restriction, no sub-occlusive episode, no steroid, no surgery, and no drug discontinuation or symptomatic response (same definition except for tolerating mild abdominal pain). Long-term endpoints were time to drug discontinuation for treatment failure and to bowel damage progression. The comparisons were performed after using propensity score analysis. Results: Seventy patients were included (34 on ustekinumab, 36 on anti-TNF). After propensity score adjustment, symptomatic remission at 6 months was achieved in 73.9% of patients receiving ustekinumab compared to 42.7% in the anti-TNF group ( Conclusion: Ustekinumab appears more effective than a second-line anti-TNF in patients with symptomatic stricturing CD after failing to respond to a first-line anti-TNF.