DOP105Efficacy of subcutaneous guselkumab in moderately to severely active ulcerative colitis by induction week 12 clinical response status: Week 48 results from the phase 3 ASTRO study

Abstract Background Guselkumab (GUS) is a selective dual-acting interleukin (IL)-23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on immune cells that produce IL-23. The phase 3, randomised, double-blind, treat-through ASTRO study (NCT05528510) evaluated subcutaneous (SC) GUS induction and maintenance therapy in patients (pts) with moderately to severely active ulcerative colitis (UC). The objective of this exploratory analysis was to evaluate clinical and endoscopic outcomes at Week (W)48 in pts who did or did not achieve clinical response to GUS SC induction therapy at W12. Methods Eligible pts had documented inadequate response or intolerance to conventional or advanced UC therapy. ASTRO used a treat-through design where pts were randomised (1:1:1) to receive GUS 400 mg SC every 4 weeks (q4w) (×3) induction→GUS 100 mg SC every 8 weeks (q8w) maintenance (Arm 1; N = 139); GUS 400 mg SC q4w (×3) induction→GUS 200 mg SC q4w maintenance (Arm 2; N = 140); or placebo SC (Arm 3; N = 139), and remained on their assigned regimen through W48 regardless of their clinical response at induction W12 (Arms 1 and 2 only). Clinical response was defined as a decrease in modified Mayo score from baseline of ≥ 30% and ≥2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or achieving a rectal bleeding subscore of 0 or 1. Clinical remission, clinical response, endoscopic response, and endoscopic remission (see Table for definitions) at W48 are reported by GUS dose regimen for GUS induction responders and GUS induction nonresponders. Results A total of 267 GUS-treated pts were included in this analysis, 67.4% (180/267) of whom achieved clinical response to GUS induction therapy at W12. At W48, among GUS induction clinical responders, clinical remission was achieved by 51.6% to 60.7%, clinical response by 74.7% to 82.0%, endoscopic improvement by 59.3% to 66.3%, and endoscopic remission by 35.2% to 41.6% (Table). At W48, among GUS induction nonresponders, clinical remission was achieved by 25.0% to 25.6%, clinical response by 48.8% to 56.8%, endoscopic improvement by 32.6% to 40.9%, and endoscopic remission by 7.0% to 25.0% (Table). Conclusion Pts who achieved clinical response after GUS SC induction had better clinical and endoscopic outcomes at W48 than those who did not achieve clinical response after induction. However, a subset of pts who were not in clinical response after induction but who continued into GUS SC maintenance did achieve clinical and endoscopic endpoints at W48, suggesting a benefit of continued GUS treatment after W12 for some pts. Conflict of interest: Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda Long, Millie: Reports research support from Lilly, Pfizer, Takeda, and Celltrion and consulting for AbbVie, Pfizer, Bristol Myers Squibb, Roivant, Johnson & Johnson, Merck, Takeda, Prometheus, Lilly, Intercept, Target RWE, Celltrion, Sanofi, and Spyre. Peyrin-Biroulet, Laurent: CONSULTING Abbvie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, LifeMine, Medac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, Ventyx. LECTURE Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots Hisamatsu, Tadakazu: Grant support: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd. Consulting: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, Abivax, MSD, Chugai. Lecture fee: Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Kissei Pharmaceutical Co. Ltd. Baker, Thomas: Employee of Johnson & Johnson. Alvarez, Yelina: Employee of Johnson & Johnson. Jiang, Lingjing: Employee of Johnson & Johnson. Zhang, Hongyan: Employee of Johnson & Johnson. Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Allegretti, Jessica R: consultant for Janssen, Pfizer, Abbvie, Vedanta, Geneteche, Seres Therapeutics, Ferring, GSK, Merck, Bristol Myer Squibb Roivant, Celltrion, TRXBio, Xencor, and Shattuck Labs Speaker for Abbvie, Janssen.