Safety of Guselkumab in Inflammatory Bowel Disease Up to 1 Year: Integrated Safety Analysis of Phase 2 and 3 Studies in Crohn’s Disease and Ulcerative Colitis

Bruce E. Sands¹, Remo Panaccione², Silvio Danese³, Julián Panés⁴, Tadakazu Hisamatsu⁵, Geert D’Haens⁶, Rian Van Rampelbergh⁷, Mobolaji Olurinde⁸, Jacqueline Yee⁸, Karissa Lozenski⁹, Thomas Baker⁸, Shadi Yarandi⁸, Matthew Germinaro⁸, Marion L. Vetter⁸, Hewei Li⁸, Mauricio Rosas Ballina¹⁰, Jessica R. Allegretti¹¹, Anita Afzali¹² and David T. Rubin¹³, ¹Icahn School of Medicine at Mount Sinai, New York, NY, USA, NY, ²University of Calgary, Calgary, AB, Canada, AB, Canada, ³Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy, Milano, Italy, ⁴Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain, Barcelona, Spain, ⁵Kyorin University School of Medicine, Tokyo, Japan, Tokyo, Japan, ⁶Amsterdam University Medical Centers, Amsterdam, The Netherlands, D’Haens, Swaziland, ⁷Johnson & Johnson, Antwerp, Belgium, Antwerp, Belgium, ⁸Johnson & Johnson, Spring House, PA, USA, PA, ⁹Johnson & Johnson, Horsham, PA, ¹⁰Actelion Research & Development, Allschwil, Switzerland, Allschwil, Switzerland, ¹¹Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, MA, ¹²University of Cincinnati, College of Medicine, Cincinnati, OH, USA, OH, ¹³University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA, IL

Meeting: ACR Convergence 2025

Keywords: Autoinflammatory diseases, clinical trial, Inflammation, Ulcers

Session Information

Date: Sunday, October 26, 2025

Title: (0233–0279) Miscellaneous Rheumatic & Inflammatory Diseases Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Guselkumab (GUS), a dual-acting interleukin (IL)-23 inhibitor that potently neutralizes IL-23 and binds to CD64 (a receptor on cells that produce IL-23), is currently approved in the United States for treatment of ulcerative colitis (UC) and worldwide for the treatment of plaque psoriasis and psoriatic arthritis. While GUS has been shown to be safe in Crohn’s disease (CD) and UC, safety results have only been reported in individual trials to date. To characterize the overall safety profile of GUS in inflammatory bowel disease (IBD), we evaluated pooled safety data from Phase 2 and 3 clinical trials of GUS in CD and UC.

Methods: Participants with moderately to severely active CD (n=1492; GALAXI 1, 2, & 3, and GRAVITI studies) or UC (n=1514; QUASAR Induction Study 1, Induction Study 2, & Maintenance Study and VEGA-GUS monotherapy arm only) were assigned to GUS 200 mg intravenous (IV) or 400 mg subcutaneous (SC) induction (GRAVITI only) at Weeks 0, 4, and 8, followed by GUS 100 mg SC every 8 weeks or 200 mg SC every 4 weeks; or placebo (PBO). SC maintenance treatment continued through approximately 1 year. GUS studies were pooled for the induction period (GALAXI, GRAVITI, & QUASAR; IV and SC, Weeks 0-12 [VEGA excluded due to no PBO control]) and through 1 year (GALAXI, GRAVITI, QUASAR, & VEGA). In this pooled analysis, safety events were normalized to 100 participant-years (PY) of follow-up with corresponding confidence intervals.

Results: Through Week 12, 1703 participants were treated with GUS with 399.9 PY of follow-up. Rates of adverse events (AEs) were similar between participants treated with GUS (200 mg IV or 400 mg SC) and PBO (Figure 1A). AEs occurred at a rate of 202.82/100 PY and 223.26/100 PY, serious AEs at 11.75/100 PY and 28.56/100 PY, AEs leading to study agent discontinuation at 5.50/100 PY and 16.32/100 PY, and serious infections at 1.50/100 PY and 1.17/100 PY, for GUS and PBO, respectively. Through 1 year, 2057 participants were treated with GUS, with 1752.1 PY of follow-up. Rates of AEs, serious AEs, AEs leading to discontinuation, and serious infections, were no higher in GUS-treated than PBO-treated participants (Figure 1B). Through 1 year, no anaphylactic or serum sickness reactions were reported, and rates of malignancy, opportunistic infection, major adverse cardiovascular event, and clinically important hepatic disorders were low (Table 1). In GUS-treated participants, one participant (from an endemic region) reported active tuberculosis, and 2 deaths (acute myocardial infarction in a participant with pre-existing cardiovascular risk factors and non-suicidal gunshot wound, respectively) occurred.

Conclusion: Through 1 year of treatment, GUS demonstrated a favorable safety profile comparable to PBO in participants with CD and UC. No new safety concerns were identified.

Figure 1. Key safety events in phase 2/3 IBD clinical studies during the induction period (Week 0-12) (A) and through 1 year (B)

Table 1: Targeted adverse events during the induction period and through 1 year; exposure-adjusted rates of events per 100 participant-years (PY) of follow-up and 95% confidence intervals (CI)

Disclosures: B. Sands: AbbVie, 2, Abivax, 2, 6, Adiso Therapeutics, 2, Agomab, 2, Alimentiv, 2, Amgen, 2, AnaptysBio, 2, Arena Pharmaceuticals, 2, Artugen Therapeutics, 2, AstraZeneca, 2, Biolojic Design, 2, Biora Therapeutics, 2, Boehringer Ingelheim, 2, Boston Pharmaceuticals, 2, Bristol Myers Squibb, 2, 5, 6, Calibr, 2, Celgene, 2, Celltrion, 2, ClostraBio, 2, Eli Lilly, 2, 6, Enthera, 2, Envied Biosciences, 2, Equillium, 2, Evommune, 2, Ferring, 2, Fiat, 2, Fresenius Kabi, 2, Galapagos, 2, Genentech (Roche), 2, Gilead Sciences, 2, Gossamer Bio, 2, GSK, 2, Imhotex, 2, Index Pharmaceuticals, 2, Innovation Pharmaceuticals, 2, Inotrem, 2, Janssen, 2, 5, 6, Kaleido, 2, Kallyope, 2, Merck, 2, Microba, 2, Mobius Care, 2, Morphic Therapeutics, 2, MRM Health, 2, Nexus Therapeutics, 2, Nimbus, 2, Odyssey, 2, Pfizer, 2, 5, 6, Progenity, 2, Prometheus Biosciences, 2, Prometheus Laboratories, 2, Protagonist Therapeutics, 2, Q32 Bio, 2, Rasayana Therapeutics, 2, Recludix Therapeutics, 2, Reistone Biopharma, 2, Sanofi, 2, Spyre Therapeutics, 2, Sun Pharma, 2, Surrozen, 2, Takeda, 2, 5, 6, Target RWE, 2, Teva, 2, Theravance Biopharma, 2, 5, 6, TLL Pharmaceutical, 2, Tr1X, 2, Union Therapeutics, 2, Ventyx Biopharma, 2, 11; R. Panaccione: AbbiVax, 2, Abbott, 2, AbbVie, 2, Alimentiv, 2, Amgen, 2, AnaptysBio, 2, Arena Pharmaceuticals, 2, AstraZeneca, 2, Biogen, 2, Boehringer Ingelheim, 2, Bristol Myers Squibb, 2, Celgene, 2, Cosmos Pharmaceuticals, 2, Eisai, 2, Elan, 2, Eli Lilly, 2, Ferring, 2, Fresenius Kabi, 2, Galapagos, 2, Genentech, 2, Gilead Sciences, 2, GSK, 2, JAMP Bio, 2, Janssen, 2, Merck, 2, Mylan, 2, Novartis, 2, Oppilan Pharma, 2, Organon, 2, Pandion Pharma, 2, Pendopharm, 2, Pfizer, 2, Progenity, 2, Prometheus Biosciences, 2, Protagonist Therapeutics, 2, Roche, 2, Sandoz, 2, Satisfai Health, 2, Shire, 2, Spyre Therapeutics, 2, Sublimity Therapeutics, 2, Takeda, 2, Theravance Biopharma, 2, Trellus, 2, UCB, 2, Union Biopharma, 2, Ventyx Biopharma, 2, Viatris, 2; S. Danese: AbbVie, 2, 6, Alimentiv, 2, Allergan, 2, Amgen, 2, 6, AstraZeneca, 2, Athos, 2, Biogen, 2, Boehringer Ingelheim, 2, Celgene, 2, Celltrion, 2, Eli Lilly, 2, Enthera, 2, Ferring, 2, 6, Gilead, 2, 6, Hospira, 2, Inotrem, 2, Janssen, 2, 6, Johnson & Johnson, 2, MSD, 2, Mundipharma, 2, Mylan, 2, 6, Pfizer, 2, 6, Roche, 2, Sandoz, 2, Sublimity Therapeutics, 2, Takeda, 2, 6, TiGenix, 2, UCB, 2, Vifor, 2; J. Panés: AbbVie, 2, Alimentiv, 2, 12, has served on a data safety monitoring board, Athos, 2, Atomwise, 2, Boehringer Ingelheim, 2, Celsius, 2, Ferring, 2, Galapagos, 2, Genentech/Roche, 2, GSK, 2, Janssen, 2, Mirum, 2, 12, has served on a data safety monitoring board, Nimbus, 2, Pfizer, 2, Progenity, 2, Prometheus, 2, Protagonist Therapeutics, 2, Revolo, 2, Sanofi, 2, 12, has served on a data safety monitoring board, Sorriso, 2, 12, has served on a data safety monitoring board, Surrozen, 2, 12, has served on a data safety monitoring board, Takeda, 2, Wasserman, 2; T. Hisamatsu: AbbVie GK, 2, 5, 6, Abivax, 2, Boston Scientific Corporation, 5, Bristol Myers Squibb, 2, EA Pharma Co. Ltd, 2, 5, 6, Gilead, 2, Janssen Pharmaceutical K.K., 2, 6, JIMRO Co. Ltd., 5, 6, Kissei Pharmaceutical Co. Ltd., 5, 6, Kyorin Pharmaceutical Co. Ltd., 5, 6, Lilly, 2, Mitsubishi Tanabe Pharma Corporation, 2, 5, 6, Mochida Pharmaceutical Co. Ltd., 5, 6, Nippon Kayaku Co. Ltd., 5, Pfizer Inc., 2, 5, 6, Takeda Pharmaceutical Co. Ltd., 5, 6, Zeria Pharmaceutical Co. Ltd., 5; G. D’Haens: AbbVie, 2, 6, 12, data monitoring board activities, Agomab, 2, AMT, 2, AstraZeneca, 2, 12, data monitoring board activities, Boehringer Ingelheim, 2, Bristol Myers Squibb, 2, 6, 12, data monitoring board activities, Celltrion, 2, Eli Lilly, 2, Exeliom, 2, Galapagos, 2, 6, 12, data monitoring board activities, Gossamerbio, 2, GSK, 2, Immunic, 2, Index, 2, Johnson & Johnson, 2, Kaleido, 2, Origo, 2, Pfizer, 2, 6, Polpharma, 2, Procise Diagnostics, 2, Progenity, 2, Prometheus Biosciences, 2, Prometheus Laboratories, 2, Protagonist Therapeutics, 2, Seres Health, 12, data monitoring board activities, Takeda, 6; R. Rampelbergh: Johnson & Johnson, 3, 11; M. Olurinde: Johnson & Johnson, 3, 11; J. Yee: Johnson & Johnson, 3, 11; K. Lozenski: BMS, 11, Johnson & Johnson, 3, 11; T. Baker: Johnson & Johnson, 3, 11; S. Yarandi: Johnson & Johnson, 3, 11; M. Germinaro: Johnson & Johnson, 3, 11; M. Vetter: Johnson & Johnson, 3, 11; H. Li: Johnson & Johnson, 3, 11; M. Ballina: Actelion Research & Development, 3, 11; J. Allegretti: AbbVie, 2, 6, Adiso, 2, Bristol Myers Squibb, 2, 6, Ferring, 2, Genentech, 2, GlaxoSmithKline, 2, Janssen, 12,, 2, 5, 6, 12, Steering committee member, Merck, 2, 5, Pfizer, 2, 5, Roivant, 2, Seres Therapeutics, 2; A. Afzali: AbbVie, 12, potential conflicts of interest, Bristol Myers Squibb, 12, potential conflicts of interest, Celgene, 12, potential conflicts of interest, DiaSorin, 12, potential conflicts of interest, Eli Lilly, 12, potential conflicts of interest, Gilead Sciences, 12, potential conflicts of interest, IBD Horizons, 12, potential conflicts of interest, Janssen, 12, potential conflicts of interest, Pfizer, 12, potential conflicts of interest, Takeda, 12, potential conflicts of interest, TLL Pharmaceuticals, 12, potential conflicts of interest; D. Rubin: AbbVie, 1, 2, 6, Altrubio, 1, 2, 6, 11, Apex, 1, 2, 6, Avalo, 1, 2, 6, 12, reports potential conflicts of interest, Bristol Myers Squibb, 1, 2, 6, Buhlmann Diagnostics Corp, 1, 2, 6, Celgene, 1, 2, 6, Connect BioPharma, 1, 2, 6, Cornerstones Health, Inc, 12, Membership on the Board of Directors, Crohn’s & Colitis Foundation, 12, Board of Trustees, Datos Health, 11, Intouch Group, 1, 2, 6, Iterative Health, 1, 2, 6, 11, Janssen (Johnson & Johnson), 1, 2, 6, 12, reports potential conflicts of interest with, Lilly, 1, 2, 6, Pfizer, 1, 2, 6, Samsung Neurologica, 1, 2, 6, Takeda, 1, 2, 5, 6.

To cite this abstract in AMA style:

Sands B, Panaccione R, Danese S, Panés J, Hisamatsu T, D’Haens G, Rampelbergh R, Olurinde M, Yee J, Lozenski K, Baker T, Yarandi S, Germinaro M, Vetter M, Li H, Ballina M, Allegretti J, Afzali A, Rubin D. Safety of Guselkumab in Inflammatory Bowel Disease Up to 1 Year: Integrated Safety Analysis of Phase 2 and 3 Studies in Crohn’s Disease and Ulcerative Colitis [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/safety-of-guselkumab-in-inflammatory-bowel-disease-up-to-1-year-integrated-safety-analysis-of-phase-2-and-3-studies-in-crohns-disease-and-ulcerative-colitis/. Accessed .

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-of-guselkumab-in-inflammatory-bowel-disease-up-to-1-year-integrated-safety-analysis-of-phase-2-and-3-studies-in-crohns-disease-and-ulcerative-colitis/