Abstract
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 (p = 0.24), while symptomatic response was observed in 84.0% and 49.5%, respectively (p = 0.13). Predictors of remission in the ustekinumab group were prior bowel resection (p = 0.001) and stricture length <12 cm (p = 0.042). The risk of treatment discontinuation (hazard ratio (HR) = 2.86 (1.33-6.15); p = 0.008) and bowel damage progression (HR = 3.90 (1.64-9.24); p = 0.003) were higher 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.