Session Information
Session Type: Poster Session B
Session Time: 10:30AM-12:30PM
Background/Purpose: Combination induction therapy with guselkumab (GUS), an interleukin (IL)-23p19 subunit antagonist, and golimumab (GOL), a tumor necrosis factor (TNFα) antagonist, induced higher rates of clinical remission, endoscopic, and histologic outcomes than either monotherapy at Week (WK)12 in patients with ulcerative colitis (VEGA NCT03662542). Data through WK38 suggested the continued benefit of combination induction even after a transition to GUS monotherapy at WK12. We explored early molecular changes in colon tissue in a subset of patients at WK4 to define mechanistic contributions of each monotherapy and combination; these parameters were evaluated again at WK38 to assess potential carry-over of efficacy.
Methods: Colon biopsies were obtained at baseline (n=195), WK4 (n=42 substudy), and WK38 (n=172). Transcriptional profiles were generated with RNA sequencing (RNAseq). Gene correlation network analysis was applied in conjunction with publicly available single cell RNAseq data to define biologically relevant bulk and cell type-specific transcriptional modules associated with molecular features of disease. Gene set variation analysis (GSVA) was used to quantitatively assess changes in biologic modules with treatment.
Results: At WK4, combination induction (n=10) showed significant (p< 0.05) decreases in molecular features compared to GUS (n=19) and GOL (n=13), including transcriptomic modules representing the IL-23 pathway, interferon response, and inflammatory epithelial and myeloid transcriptional states associated with endoscopic improvement at WK4 (Mayo endoscopy subscore of 0 or 1) (combination 5/11, GOL 1/13; GUS 2/19). Reduction (p< 0.05) in inflammatory modules persisted through WK38 with combination vs monotherapy induction. Module changes between treatments at WK4 indicated a stronger correlation between GUS and combination (R=0.8; p=2.2e-16) than GOL and combination (R=0.52; p=4.1e-12), with processes associated with epithelial and stromal biology, and mucosal inflammation. In contrast, the combination effect on specific neutrophil/myeloid biology at WK4 was more similar to GOL than GUS, supporting the early role of GOL in targeting innate inflammation.
Conclusion: Combination induction with GUS and GOL showed significant reductions in major inflammatory features of disease as early as WK4 which persisted through WK38 with GUS maintenance. Correlative analysis supports the role of GUS as the primary driver of tissue healing, with GOL further contributing to innate inflammatory activity, which demonstrate differential and complementary mechanisms of action of TNFα and IL-23p19 subunit blockade.
Disclosures: D. Richards: Janssen, 3, Johnson & Johnson, 11; M. Vetter: Janssen, 3, Johnson & Johnson, 11; M. Germinaro: Janssen, 3, Johnson & Johnson, 11; B. Verstockt: AbbVie, 5, 12, Consultancy fees, speaker's fees, Alimentiv, 12, Consultancy fees, Applied Strategic, 12, Consultancy fees, Atheneum, 12, Consultancy fees, BenevolentAI, 12, Consultancy fees, Biogen, 12, Speaker’s fees, Biora Therapeutics, 5, 12, Consultancy fees, Bristol Myers Squibb, 12, Speaker’s fees, consultancy fees, CelltrionSpeaker’s fees, 12, Speaker’s fees, Chiesi, 12, Speaker’s fees, Falk, 12, Speaker’s fees, Ferring, 12, Speaker’s fees, Galapagos, 12, Speaker’s fees, consulting fees, Guidepont, 12, Consultancy fees, Inotrem, 12, Consultancy fees, Ipsos, 12, Consultancy fees, Janssen, 12, Speaker’s fees, consulting fees, Landos, 5, 12, Consultancy fees, Lily, 12, Speaker’s fees, consulting fees, MSD, 12, Speaker’s fees, Mylan, 12, Consultancy fees, Pfizer, 5, 12, Speaker’s fees, consultancy fees, Progenity, 12, Consultancy fees, R-Biopharm, 12, Speaker’s fees, Sandoz, 12, Speaker’s fees, consultancy fees, Santa Ana Bio, 12, Consultancy fees, Sosei Heptares, 12, Consultancy fees, Sossei Heptares, 5, Takeda, 5, 12, Speaker’s fees, consulting fees, Tillots Pharma, 12, Speaker’s fees, consultancy fees, Truvion, 12, Speaker’s fees, Viatris, 12, Speaker’s fees, consultancy fees; R. Atreya: AbbVie, 12, Paid or unpaid consultant or honoraria, Amgen, 12, Paid or unpaid consultant or honoraria, Arena Pharmaceuticals, 2, Biogen, 12, Paid or unpaid consultant or honoraria, Boehringer-Ingelheim, 12, Paid or unpaid consultant or honoraria, Bristol-Myers Squibb, 12, Paid or unpaid consultant or honoraria, Celgene, 12, Paid or unpaid consultant or honoraria, Celltrion Healthcare, 12, Paid or unpaid consultant or honoraria, DrFalk Pharma, 12, Paid or unpaid consultant or honoraria, Ferring, 12, Paid or unpaid consultant or honoraria, Fresenius Kabi, 12, Paid or unpaid consultant or honoraria, Galapagos, 12, Paid or unpaid consultant or honoraria, Gilead, 12, Paid or unpaid consultant or honoraria, GlaxoSmithKlein(GSK), 12, Paid or unpaid consultant or honoraria, InDex Pharmaceuticals, 12, Paid or unpaid consultant or honoraria, Janssen, 12, Paid or unpaid consultant or honoraria, Kiniksa Pharmaceuticals, 12, Paid or unpaid consultant or honoraria, Merck Sharp & Dohme, 12, Paid or unpaid consultant or honoraria, Novartis, 12, Paid or unpaid consultant or honoraria, Pfizer, 12, Paid or unpaid consultant or honoraria, Roche Pharma, 12, Paid or unpaid consultant or honoraria, Samsung Bioepis, 12, Paid or unpaid consultant or honoraria, Stelic, 12, Paid or unpaid consultant or honoraria, Sterna Biologicals, 12, Paid or unpaid consultant or honoraria, Takeda, 12, Paid or unpaid consultant or honoraria, Tillotts, 12, Paid or unpaid consultant or honoraria; J. Panés: Abbott, 6, AbbVie, 5, 12, Consulting fees, support for travel to meetings during the conduct of the study, Alimentive, 12, Participated on a Data Safety Monitoring Board or Advisory Board, Arena, 2, 12, Consulting fees, Athos, 12, Consulting fees, Atomwise, 12, Consulting fees, Boehringer-Ingelheim, 12, Consulting fees, Celgene, 12, Consulting fees, Celltrion, 12, Consulting fees, Ferring, 12, Consulting fees, Galapagos, 12, Consulting fees, Genentech/Roche, 12, Consulting fees, GlaxoSmithKline, 12, Consulting fees, Janssen, 6, 12, Consulting fees, Mirum, 12, Consulting fees, Morphic, 12, Consulting fees, Neste, 2, Origo, 12, Consulting fees, Pandion, 12, Consulting fees, Pfizer, 5, 12, Consulting fees, Progenity, 12, Consulting fees, Protagonist Therapeutics Inc., 12, Consulting fees, Revolo, 12, Consulting fees, Robarts, 12, Consulting fees, Sanofi, 12, Participated on a data safety monitoring board or advisory board, Takeda, 12, Consulting fees, support for travel to meetings during the conduct of the study, TGenix, 2, Theravance, 12, Consulting fees, Wassermann, 12, Consulting fees; B. Sands: AbbVie, 12, Consultant or speaker’s fees, Abivax, 12, Consulting or speaking fees, Adiso Therapeutics, 12, Consultant or speaker’s fees, AgomAb, 12, Consultant or speaker’s fees, Alimentiv, 12, Consultant or speaker’s fees, Amgen, 12, Consultant or speaker’s fees, Arena Pharmaceuticals, 12, Consultant or speaker’s fees, Artizan Biosciences, 12, Consultant or speaker’s fees, Artugen Therapeutics, 12, Consultant or speaker’s fees, AstraZeneca, 12, Consultant or speaker’s fees, Bacainn Therapeutics, 12, Consultant or speaker’s fees, Biora Therapeutics, 12, Consultant or speaker’s fees, Boehringer Ingelheim, 12, Consultant or speaker’s fees, Boston Pharmaceuticals, 12, Consultant or speaker’s fees, Bristol-Myers Squibb, 12, Consultant or speaker’s fees, Calibr, 12, Consultant or speaker’s fees, Celltrion, 12, Consultant or speaker’s fees, ClostraBio, 12, Consultant or speaker’s fees, Connect Biopharm, 12, Consultant or speaker’s fees, Cytoki Pharma, 12, Consultant or speaker’s fees, Eli Lilly and Company, 12, Consultant or speaker’s fees, Enthera, 12, Consultant or speaker’s fees, Evommune, 12, Consultant or speaker’s fees, Fresenius Kabi, 12, Consultant or speaker’s fees, Galapagos, 12, Consultant or speaker’s fees, Genentech, 12, Consultant or speaker’s fees, Gilead Sciences, 12, Consultant or speaker’s fees, GlaxoSmithKline, 12, Consultant or speaker’s fees, Gossamer Bio, 12, Consultant or speaker’s fees, HMP Acquisition, 12, Consultant or speaker’s fees, Imhotex, 12, Consultant or speaker’s fees, Immunic, 12, Consultant or speaker’s fees, Index Pharmaceuticals, 12, Consultant or speaker’s fees, Innovation Pharmaceuticals, 12, Consultant or speaker’s fees, Inotrem, 12, Consultant or speaker’s fees, Ironwood Pharmaceuticals, 12, Consultant or speaker’s fees, Janssen, 12, Consultant or speaker’s fees, Johnson & Johnson, 12, Consultant or speaker’s fees, Kaleido, 12, Consultant or speaker’s fees, Kallyope, 12, Consultant or speaker’s fees, Merck, 12, Consultant or speaker’s fees, MiroBio, 12, Consultant or speaker’s fees, Morphic Therapeutics, 12, Consultant or speaker’s fees, MRM Health, 12, Consultant or speaker’s fees, OSE Immunotherapeutics, 12, Consultant or speaker’s fees, Pfizer, 12, Consultant or speaker’s fees, Progenity, 12, Consultant or speaker’s fees, Prometheus Biosciences, 12, Consultant or speaker’s fees, Prometheus Laboratories, 12, Consultant or speaker’s fees, Protagonist Therapeutics, 12, Consultant or speaker’s fees, Q32 Bio, 12, Consultant or speaker’s fees, RedHill Biopharma, 12, Consultant or speaker’s fees, Sun Pharma Global, 12, Consultant or speaker’s fees, Surrozen, 12, Consultant or speaker’s fees, Synlogic Operating Company, 12, Consultant or speaker’s fees, Takeda, 12, Consultant or speaker’s fees, Target RWE, 12, Consultant or speaker’s fees, Theravance Biopharma, 12, Consultant or speaker’s fees, TLL Pharmaceutical, 12, Consultant or speaker’s fees, USWM Enterprises, 12, Consultant or speaker’s fees, Ventyx Biosciences, 11, 12, Consultant or speaker’s fees, Viela Bio, 12, Consultant or speaker’s fees; B. Feagan: AbbVie, 6, 12, Consulting fees, received support for attending meetings or for travel, participated on a data safety monitoring board or advisory board, AbolerIS, 12, Consulting fees, AgomAB Therapeutics, 12, Consulting fees, Allianthera, 12, Consulting fees, Amgen, 12, Consulting fees, participated on a data safety monitoring board or advisory board, AMT, 12, Participated on a data safety monitoring board or advisory board, AnaptysBio, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Applied Molecular Transport, 12, Consulting fees, Arena Pharma, 12, Consulting fees, Atomwise, 12, mConsulting fees, Avoro Capital Advisors, 12, Consulting fees, Axio Research, 12, Participated on a data safety monitoring board or advisory board, BioJamp, 12, Consulting fees, Biora Therapeutics, 12, Consulting fees, Boehringer-Ingelheim, 12, Consulting fees, support for attending meetings or for travel, participated on a data safety monitoring board or advisory board, Boxer, 12, Consulting fees, Celgene/Bristol-Myers Squibb, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Celsius Therapeutics, 12, Consulting fees, Connect BioPharma, 12, Consulting fees, Cytoki, 12, Consulting fees, Disc Medicine, 12, Consulting fees, Duality, 12, Consulting fees, EcoR1, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Eli Lilly, 12, Participated on a data safety monitoring board or advisory board, Equillium, 12, Consulting fees, Ermium, 12, Consulting fees, First Wave, 12, Consulting fees, First Word Group, 12, Consulting fees, Galapagos, 12, Consulting fees, Galen Atlantica, 12, Consulting fees, Genentech/Roche, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Gilead, 12, Consulting fees, GlaxoSmithKline, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Gossamer Pharma, 11, 12, Consulting fees, Hinge Bio, 12, Consulting fees, Hot Spot Therapeutics, 12, Consulting fees, Imhotex, 12, Consulting fees, Immunic Therapeutics, 12, Consulting fees, Index Pharma, 12, Consulting fees, participated on a data safety monitoring board or advisory board, JAKAcademy, 12, Consulting fees, Janssen, 6, 12, Consulting fees, support for attending meetings or for travel, participated on a data safety monitoring board or advisory board, Japan Tobacco Inc, 12, Consulting fees, Kaleido Biosciences, 12, Consulting fees, Landos Biopharma, 12, Consulting fees, Leadiant, 12, Consulting fees, LEK Consulting, 12, Consulting fees, Lenczner Slaght, 12, Payment for expert testimony, LifeSci Capital, 12, Consulting fees, Lument AB, 12, Consulting fees, Millennium, 12, Consulting fees, MiroBio, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Morgan Lewis, 12, Payment for expert testimony, Morphic Therapeutics, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Mylan, 12, Consulting fees, OM Pharma, 12, Consulting fees, Origo, 12, Participated on a data safety monitoring board or advisory board, Orphagen, 12, Consulting fees, Pandion Therapeutics, 12, Pandion Therapeutics, Pendopharm, 12, Consulting fees, Pfizer, 12, Consulting fees, support for attending meetings or for travel, participated on a data safety monitoring board or advisory board, PlayToKnow, 12, Consulting fees, Progenity, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Prometheus Therapeutics and Diagnostics, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Protagonist, 12, Consulting fees, PTM Therapeutics, 12, Consulting fees, Q32 Bio, 12, Consulting fees, Rebiotix, 12, Consulting fees, REDX, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Roche, 12, Consulting fees, Sandoz, 12, Consulting fees, Sanofi, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Seres Therapeutics, 12, Consulting fees, Silverback Therapeutics, 12, Consulting fees, Surrozen, 12, Consulting fees, Takeda, 6, 12, Consulting fees, support for attending meetings or for travel, participated on a data safety monitoring board or advisory board, Teva, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Thelium, 12, Consulting fees, Tigenix, 12, Consulting fees, Tillotts Pharma, 12, Consulting fees, participated on a data safety monitoring board or advisory board, Ventyx Biosciences, 12, Consulting fees, VHSquared Ltd., 12, Consulting fees, Viatris, 12, Consulting fees, Ysios, 12, Consulting fees, Ysopia, 12, Consulting fees, Zealand Pharma, 12, Consulting fees; B. McRae: Janssen, 3, Johnson & Johnson, 11; D. Cua: Janssen, 3, Johnson & Johnson, 11; P. Branigan: Janssen, 3, Johnson & Johnson, 11; T. Freeman: Janssen, 3, 11, Johnson & Johnson, 11.
To cite this abstract in AMA style:
Richards D, Vetter M, Germinaro M, Verstockt B, Atreya R, Panés J, Sands B, Feagan B, McRae B, Cua D, Branigan P, Freeman T. Guselkumab and Golimumab Combination Induction Therapy in Ulcerative Colitis Results in Early Local Tissue Healing That Is Sustained Through Guselkumab Maintenance Therapy [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/guselkumab-and-golimumab-combination-induction-therapy-in-ulcerative-colitis-results-in-early-local-tissue-healing-that-is-sustained-through-guselkumab-maintenance-therapy/. Accessed .« Back to ACR Convergence 2024
ACR Meeting Abstracts - https://acrabstracts.org/abstract/guselkumab-and-golimumab-combination-induction-therapy-in-ulcerative-colitis-results-in-early-local-tissue-healing-that-is-sustained-through-guselkumab-maintenance-therapy/