P0586Indirect Comparison of Afimkibart and Adalimumab Treatment Effects in Patients with Ulcerative Colitis Using Data from TUSCANY-2 and HIBISCUS

Background Advanced therapies for ulcerative colitis (UC) continue to emerge, creating a complex and growing landscape of treatment options. Afimkibart, a TL1Abinding antibody, demonstrated promising efficacy in TUSCANY-2, a phase 2b trial1. We utilize indirect comparison methods to compare the efficacy of afimkibart versus adalimumab, an anti-TNF therapy, as firstline therapeutics. Methods We performed a post hoc analysis using propensity score (PS) matching across the active arms of TUSCANY2 (NCT04090411) and HIBISCUS I/II (NCT02163759/NCT02171429), two phase 3 trials1,2, to compare the efficacy of afimkibart versus adalimumab among patients who did not previously receive any biologic therapy. Outcomes included clinical remission (defined as stool frequency subscore = 0 or 1; rectal bleeding subscore = 0; and endoscopic subscore = 0 or 1), clinical response, endoscopic improvement, and endoscopic remission after an induction period of 10 or 14 weeks, respectively. PS matching (1:1) adjusted for baseline modified Mayo score, disease duration, baseline corticosteroid use, age, sex, disease extent, and region. Results Patients who met the inclusion criteria for both studies were included in this analysis. In HIBISCUS I/II, 273 patients received adalimumab and 139 received placebo; in TUSCANY2, 101 received afimkibart and 24 received placebo. Before matching, clinical remission rates were 26.0% for adalimumab vs 10.8% for placebo in HIBISCUS I/II, and 41.6% for afimkibart vs 16.7% for placebo in TUSCANY-2. After PS matching, 152 biologicnaïve patients were included in the efficacy comparison. Afimkibart demonstrated significantly greater improvement versus adalimumab (clinical remission risk difference (RD)=19.7% [95% CI 4.9-34.6], endoscopic improvement RD = 26.3% [95% CI 11.2-41.5]) in this population. Findings were directionally consistent across clinical response and endoscopic remission. Results did not change substantively with different covariate sets and model specifications. Conclusion This is the first analysis to use clinical trial data and PS methods to compare the efficacy of afimkibart with other biologics in UC. In the absence of head-to-head trials, we leveraged PS adjustment methods to generate robust comparisons of therapeutic effects, accounting for differences in baseline covariates between trials. It is worth noting that histological and lab data were not included in the PS modeling due to limited availability, and residual confounding by them and other unmeasured factors cannot be entirely ruled out. Overall, afimkibart showed greater improvement across clinical and endoscopic endpoints compared to adalimumab in biologic-naïve patients. References: 1. Danese S, Allegretti JR, Schreiber S, et al. Anti-TL1A antibody, afimkibart, in moderately-to-severely active ulcerative colitis (TUSCANY-2): a multicentre, double-blind, treat-through, multi-dose, randomised, placebo-controlled, phase 2b trial. The Lancet Gastroenterology & Hepatology. 2025;10(10):882–895. 2. Rubin DT, Dotan I, DuVall A, et al. Etrolizumab versus adalimumab or placebo as induction therapy for moderately to severely active ulcerative colitis (HIBISCUS): two phase 3 randomised, controlled trials. The Lancet Gastroenterology & Hepatology. 2022;7(1):17-27. Conflict of interest: Xu, Qixiang: No conflict of interest Manickam, Vishal A.: Inventions Disclosure: (filed by Georgia Tech Research Corporation) 1.Patent application #: PCT/US25/15014. oInventors: Chan, L.W., Manickam, V.A. oDescription: Compositions and methods for sensing enzymatic activity. 2.Patent application #: PCT/US25/15031. oInventors: Chan, L.W., Manickam, V.A. oDescription: Multiplexed volatile-releasing probes and uses thereof. Dr. Li, Yihao: Yihao Li is a current employee of Genentech, Inc. and shareholder in F. Hoffmann-La Roche, Ltd. Levitte, Steven: Employee at Genentech Inc. Zhang, Jiameng: Employee of Roche/Genentech. Park, Kt: I am an employee of Genentech Inc, and shareholder in the Roche Group.