OP10Symptomatic improvement with intravenous guselkumab induction therapy is observed early in patients with moderately to severely active Ulcerative Colitis: post-hoc analysis of QUASAR

Abstract Background Ulcerative colitis (UC) symptoms of stool frequency, rectal bleeding, and abdominal pain significantly impair quality of life. The STRIDE-II treat-to-target framework includes symptomatic relief as a short-term therapeutic goal in UC management.1,2 Early symptomatic improvement is clinically meaningful, as it influences patient satisfaction, adherence, and long-term outcomes. Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that potently neutralises IL-23 and binds to CD64, a receptor on cells that produce IL-23. We evaluated early symptomatic improvement and remission following GUS induction in clinical trial participants (pts) with moderately to severely active UC. Methods In the 12-week Phase 3, randomised, double-blind QUASAR induction study (NCT04033445), pts with moderately to severely active UC received intravenous (IV) GUS 200 mg or placebo (PBO) at Weeks (W)0, 4, and 8.3 This post-hoc analysis evaluated change from baseline in Mayo stool frequency (SFS) and rectal bleeding (RBS) subscores (per daily patient-reported outcome PRO-2 data) and proportions of pts (observed-case data) achieving symptomatic response (decrease in symptomatic Mayo score sum of SFS and RBS by ≥ 30% and ≥1 point) and remission (SFS of 0 or 1; RBS of 0) within the first 14 days of treatment. Mixed-Effect Model for Repeated Measures was used to estimate least-squares (LS) mean differences in SFS and RBS changes with GUS vs PBO. W2 data with subcutaneous (SC) GUS 400 mg induction (W0,4,8) are from the Phase 3, placebo-controlled ASTRO study (NCT05528510).4 Results The QUASAR full analysis set included 701 pts. By Day (D)6, pts receiving GUS had greater improvements in SFS (LS mean difference: -0.122 95CI: -0.240, -0.005, p = 0.041) and RBS (-0.124 -0.239, -0.009, p = 0.034) compared with PBO (Fig. 1). At D14, LS mean differences vs PBO were -0.180 (95CI: -0.306, -0.055) for SFS (p = 0.005) and -0.280 (-0.406, -0.155) for RBS (p 0.001). At D6 and D14, 29.5% (114/387) and 41.7% (160/384) of GUS vs 22.0% (54/245) and 26.4% (64/242) of PBO pts, respectively, achieved symptomatic response (both p 0.05); 7.8% (31/395) and 13.3% (52/392) of GUS vs 4.8% (12/249) and 10.1% (25/248) of PBO pts, respectively, achieved symptomatic remission (both p 0.05) (Fig. 2). With SC induction (ASTRO), 35.8% of SC GUS vs 25.9% of PBO pts were in symptomatic response at W2; 12.2% vs 7.9%, respectively, were in symptomatic remission.4 Conclusion Pts treated with GUS had rapid improvements in SFS and RBS - clinically meaningful indicators of UC activity - as early as D6 after IV induction. These findings underscore the clinical relevance of early symptom control and align with STRIDE-II short-term treatment targets. Study support: Johnson 160:157083. 2.Dignass A, Rath S, Kleindienst T, Stallmach A. Review article: Translating STRIDE-II into clinical reality - Opportunities and challenges. Aliment Pharmacol Ther. 2023;58:492502. 3.Rubin DT, Allegretti JR, Panés J, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405:33-49. 4.Long M, Allegretti JR, Danese S, et al. Efficacy and safety of subcutaneous guselkumab induction therapy in participants with moderately to severely active ulcerative colitis: results from the randomised, placebo-controlled, phase 3 ASTRO study. Lancet Gastro Hep. 2025 In Press. Conflict of interest: Dignass, Axel: Fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees from Abivax, AbbVie, Falk, Galapagos, Gilead, J&J, Pfizer and Takeda consultancy fees from AbbVie, Alfasigma, Amgen, Biogen, Boehringer Hexal, J&J, Lilly, MSD, Pfizer, Pharmacosmos, Roche, Sandoz, Stada, Takeda, and Vifor Pharma payment from lectures including service on speakers bureaus from AbbVie, Alfasigma, Biogen, CED Service GmbH, Celltrion, Falk, Fresenius Kabi, Ferring, Galapagos, Gilead, Hexal, High5MD, J&J, Materia Prima, MedToday, MSD, Pfizer, Sandoz, Streamed-Up, Takeda, and Vifor Pharma payment for manuscript preparation from Abbvie, Falk, J&J, Takeda, Thieme, and UniMed Verlag Hirai, Fumihito: Grant support from AbbVie, Daiichi-Sankyo, EA Pharma Co, Ltd. JIMRO, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co., Ltd. Consulting fees from Bristol Myers Squibb, EA Pharma Co, Ltd., Eli Lilly, Gilead Sciences, and Johnson & Johnson. Lecture fees from AbbVie, EA Pharma Co, Ltd., Kissei Pharmaceutical Co, Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd, and Takeda Pharmaceutical Co., Ltd. Saruta, Masayuki: Grants or contracts from AbbVie GK, CMIC CMO Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., PPD-SNBL K.K., and Zeria Pharmaceutical Co., Ltd. payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from AbbVie GK, EA Pharma Co., Ltd., Gilead Sciences K.K., Johnson & Johnson, Pharmaceutical K.K., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nobelpharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Viatris Pharmaceutical Co., Ltd. Sasaki, Ayako: Employee of Johnson & Johnson Yoshigoe, Shinichi: Employee of Johnson & Johnson Zhuo, Jianmin: Employee of Johnson & Johnson Yang, Yishen: Employee of Johnson & Johnson Herr, Keira: Employee of Johnson & Johnson Hisamatsu, Tadakazu: Grant support from AbbVie, Daiichi-Sankyo, EA Pharma Co, Ltd. JIMRO, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co., Ltd. Consulting fees from Bristol Myers Squibb, EA Pharma Co, Ltd., Eli Lilly, Gilead Sciences and Johnson & Johnson. Lecture fees from AbbVie, EA Pharma Co, Ltd., Kissei Pharmaceutical Co, Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.