P1102Impact of Disease Duration on Clinical and Endoscopic Responses at 1 Year in Patients with Crohn’s Disease Treated with Guselkumab: Pooled Analysis of the GALAXI 2 & 3 Studies

Background Shorter disease duration at biologic treatment initiation has been associated with improved therapeutic outcomes in Crohn’s disease (CD).1,2 Using pooled data from two randomized clinical trials, we evaluated whether disease duration impacts achievement of clinical and endoscopic outcomes in adults with active CD treated with guselkumab (GUS). Methods Post-hoc analyses used pooled data from the Phase 2/3 GALAXI 2 & 3 studies in adults with moderately to severely active CD randomized to intravenous GUS 200mg at week (W) 0, W4, W8, followed by subcutaneous GUS 100mg every 8W (Q8W) from W16-40 or GUS 200mg Q4W from W12-44. Analyses were stratified by baseline (BL) disease duration: ultrashort (USDD; ≤1 year), intermediate-short (ISDD; >1 to ≤ 2 years), intermediate-long (ILDD; >2 to ≤ 5 years), and long (LDD; >5 years) disease duration. Rates for clinical response (100-point decrease from BL in CD Activity Index [CDAI] or CDAI<150), clinical remission (CDAI<150), endoscopic response (≥50% improvement from BL in Simple Endoscopic Score for CD [SES-CD] or SES-CD≤2), endoscopic remission (SES-CD≤4, ≥2-point reduction from BL in SES-CD, and no SES-CD sub-score >1), and deep remission (clinical and endoscopic remission) were evaluated at W12 (placebo-controlled period) and W48. Results Despite numerical differences, BL characteristics were generally balanced across disease duration subgroups; as expected, increasingly higher proportions of patients with a history of inadequate response or intolerance to biologic therapies were observed with longer disease duration (Table 1). At W12, GUS induction therapy was effective irrespective of disease duration (data not shown). Achievement rates in the pooled GUS groups increased through W48, with rates of clinical response (range: 74% to 78%), clinical remission (range: 65% to 73%), and endoscopic response (range: 47% to 54%) being comparable across disease duration subgroups. A clinically relevant trend toward lower rates of endoscopic remission (USDD: 44%; ISDD: 41%; ILDD: 35%; LDD: 31%) and deep remission (USDD: 43%; ISDD: 37%; ILDD: 29%; LDD: 28%) was observed with longer disease duration (Figure 1). Conclusion Among adults with moderately to severely active CD from GALAXI 2 & 3, GUS demonstrated clinical and endoscopic benefits across disease duration subgroups with increasing rates through 1 year. A trend toward lower rates of endoscopic/deep remission at 1 year was observed in patients with longer disease duration, supporting earlier initiation of GUS treatment in the disease course. References: 1. Peyrin-Biroulet L, Colombel JF, Louis E, et al. Shorter Crohn’s Disease Duration Is Associated With Better Clinical and Endoscopic Outcomes With Risankizumab in Phase 3 Studies. Gastro Hep Adv. 2024;3(4):539-550. Published 2024 Mar 7. doi:10.1016/j.gastha.2024.02.008 2. Faleck DM, Winters A, Chablaney S, et al. Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn’s Disease But Not Ulcerative Colitis. Clin Gastroenterol Hepatol. 2019;17(12):2497-2505.e1. doi:10.1016/j.cgh.2018.12.040 Conflict of interest: Ferrante, Marc: Research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Atreya, Raja: Served as a paid or unpaid consultant for or received honoraria from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Ferring, Fresenius Kabi, Galapagos, Gilead, GlaxoSmithKline, InDex Pharmaceuticals, Johnson & Johnson, Kliniksa Pharmaceuticals, Merk Sharp & Dohme, Novartis, Pfizer, Roche, Samsung Bioepsis, Stelic, Sterna Biologicals, Takeda, and Tillotts. Van Rampelbergh, Rian: Employee of Johnson & Johnson Van Duijnhoven, Wilbert: Employee of Johnson & Johnson (and stock holder) Bravatà, Ivana: Johnson Johnson employee Nazar, Maciek: Employee of Johnson & Johnson Van Denderen, Jacqueline: Employee of Johnson & Johnson Mccaffrey, Victoria: Employee of Johnson & Johnson Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda