Comparative effectiveness and safety of risankizumab vs ustekinumab in patients with Crohn's disease: a propensity score-matched multicenter retrospective cohort study.

BACKGROUND: In the SEQUENCE trial, risankizumab was non-inferior for clinical remission and superior for endoscopic remission compared to ustekinumab in anti-TNF-exposed Crohn's disease (CD) patients. Given unclear results in real-world settings, we aimed to evaluate whether these findings translate to real-world advanced therapy-exposed and naïve CD cohorts. METHODS: A retrospective cohort study using the TriNetX database with 1:1 propensity-score matching (PSM) analyzed 2 CD cohorts (advanced therapy-exposed and naïve) from inception to March 29, 2026. Primary outcomes were corticosteroid use, hospitalization, emergency department (ED) visits, intestinal surgery, intestinal complications, C-reactive protein (CRP) ≥ 10 mg/L, and therapy switching. Secondary outcomes included venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and opportunistic infections. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with outcomes assessed at 12 and 24 months. RESULTS: After PSM, each group in the advanced therapy-exposed cohort comprised 1799 patients, and each group in the advanced therapy-naïve cohort comprised 1776 patients. In the advanced therapy-exposed cohort, compared with ustekinumab, the risankizumab group had a statistically significant lower odds of ED visits, intestinal fistula, CRP ≥10 mg/L, MACE, and opportunistic infections at 12 months, while hospitalization (OR = 0.67, 95% CI, 0.50-0.91), ED visits (OR = 0.49, 95% CI, 0.35-0.68), overall intestinal surgery (OR = 0.68, 95% CI, 0.52-0.90), small intestine surgery (OR = 0.71, 95% CI, 0.52-0.99), large intestine surgery (OR = 0.72, 95% CI, 0.53-0.97), intestinal obstruction (OR = 0.69, 95% CI, 0.51-0.93), intestinal fistula (OR = 0.53, 95% CI, 0.36-0.78), CRP ≥10 mg/L (OR: 0.62, 95% CI, 0.46-0.85), MACE, and opportunistic infections at 24 months. Similarly, in the naïve cohort, compared with ustekinumab, risankizumab had a statistically significant lower odds of only CRP ≥10 mg/L at 12 months, while hospitalization, ED visits, overall intestinal surgery, small intestine surgery, large intestine surgery, anal surgery, overall complication of intestines, intestinal obstruction, switching to another advanced therapy, CRP ≥10 mg/L, and opportunistic infections at 24 months. CONCLUSIONS: In real-world practice, risankizumab was associated with modestly more favorable outcomes in patients with prior advanced therapy exposure, whereas differences became more apparent at 24 months in advanced therapy-naïve patients. Prospective studies are needed to confirm these findings.