S1455 Real-World Comparative Effectiveness of Vedolizumab vs Upadacitinib and Risankizumab for Crohn’s Disease Through 52 Weeks

Introduction: In a previous cohort study, upadacitinib (UPA) and risankizumab (RISA) demonstrated similar effectiveness for Crohn’s disease (CD). We now compare vedolizumab (VEDO) to UPA and RISA. Methods: In this retrospective cohort study, adults initiated VEDO, UPA, or RISA for active CD at a large academic center in 2023. Participants (pts) were excluded if treatment was to prevent post-op recurrence or if the Harvey-Bradshaw Index was <5 (unless on corticosteroids). Co-primary outcomes were steroid-free clinical remission (SFCR) and treatment discontinuation at 52 (±4) weeks (wks). Secondary outcomes were SFCR at 12 (±4) wks, clinical response (CR) at 12 and 52 (±4) wks, and endoscopic/radiologic response. Additional descriptive outcomes were bowel resection surgeries and adverse events (AEs). Treatment discontinuation was evaluated using Cox regression and competing-risks regression, where discontinuation due to AEs was treated as a competing risk. Other outcomes were evaluated using logistic regression. Inverse probability of treatment weighting (IPTW) adjusted for confounders. Two independent comparisons were conducted: VEDO vs UPA and VEDO vs RISA. Results: Among 291 pts, 72 received VEDO, 67 UPA, and 152 RISA. VEDO pts were younger, had less penetrating disease, and had fewer prior biologics. Unadjusted outcomes were similar for VEDO vs UPA, but RISA had higher CR at 52 wks (80% vs 60%, P < 0.01), fewer discontinuations (18% vs 32%, P = 0.02), and fewer AEs (20% vs 33%, P = 0.04) vs VEDO. IPTW confirmed covariate balance. Competing risks regression showed similar discontinuation for non-response for VEDO vs UPA, but higher discontinuation for VEDO vs RISA. In IPTW models, VEDO had lower odds of CR at 12 wks vs UPA (OR 0.36, P = 0.02). Compared to RISA, VEDO had lower odds of CR at 12 wks (OR 0.51, P = 0.04), CR at 52 wks (OR 0.32, P < 0.01), SFCR at 52 wks (OR 0.44, P = 0.01), and endoscopic response (OR 0.28, P = 0.01), and higher hazard of treatment discontinuation (HR 2.18, P = 0.01). Common AEs: VEDO, infections (12/24), arthralgias (6/24); UPA, rashes (10/26), infections (7/26); RISA, infections (13/32), rashes (5/32). Conclusion: UPA was more likely than VEDO to achieve CR at 12 wks, but no differences were observed at 52 wks, possibly due to power. RISA was more effective than VEDO at both 12 and 52 wks. No new safety concerns emerged. Large, prospective studies are needed to confirm these findings.