DOP071Multi-omics biomarkers for predicting treatment response in inflammatory bowel disease

Abstract Background Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated disorders characterized by heterogeneous clinical courses and unpredictable therapeutic responses. Despite the availability of biologics and small molecules, treatment selection remains empirical, delaying remission, increasing exposure to ineffective drugs, and highlighting urgent need for biomarker-driven, precision-guided strategies. Methods A multi-omics analysis was performed, integrating transcriptomics, proteomics, metabolomics, and metagenomic across intestinal tissue, serum, urine, serum-derived extracellular vesicles (EVs), and stool from 130 IBD patients treated with anti-TNFα, ustekinumab, vedolizumab, or tofacitinib (Figure 1). Results Clinical and demographic characteristics are summarised in Table 1. Analyses revealed distinct, therapy-specific molecular signatures capable of discriminating responders from non-responders, with all markers achieving a predictive performance of area under the curve 0.9. In CD, PDIA1 and IGHV4-28 in serum EVs and intestinal tissue predicted anti-TNFα response, while LINC02802 and MIR567 distinguished ustekinumab responders. In UC, vedolizumab response was associated with SCIMP and CYP39A1 in intestinal tissue, and tofacitinib response with CAVN2 in serum EVs. Metabolomic profiling highlighted coordinated serum and urinary alterations in amino acids, organic acids, and lipid metabolism linked to therapeutic efficacy. Metagenomic analysis identified genera associated with response, including Prevotella and Anaerotruncus for anti-TNFα, Faecalibacterium for ustekinumab, Catenibacterium for vedolizumab, and Phascolarctobacterium for tofacitinib. Integration of multi-omics layers provided complementary insights, emphasizing the central role of the intestinal microenvironment and host-microbiota interactions in mediating treatment outcomes. Conclusion These findings establish a comprehensive framework for precision therapy in IBD, identifying predictive biomarkers with translational potential to optimize personalized therapy, minimize ineffective treatment, and reduce disease burden. Conflict of interest: Baldan-Martin, Montserrat: No conflict of interest Azkargorta, Mikel: No conflict of interest Aransay, Ana M.: No conflict of interest Gil-Redondo, Rubén: No conflict of interest Moreno-Indias, Isabel: No conflict of interest Iloro, Ibon: No conflict of interest Martínez González, Paula Julia: No conflict of interest Soleto, Irene: No conflict of interest Suarez-Trujillo, Fabio: No conflict of interest Ramírez, Cristina: No conflict of interest Lucendo, Alfredo: No conflict of interest Rodríguez Gutiérrez, Cristina: No conflict of interest Gutiérrez Casbas, Ana: No conflict of interest Martin Arranz, Eduardo: Personal Fees: Olympus and Janssen Non-financial Support: Support for conference attendance, education or research from Abbvie, Pfizer, Janssen Bujanda, Luis: Not Rodríguez-Lago, Iago: No conflict of interest De Francisco Garcia, Ruth Maria: No conflict of interest Iglesias Flores, Eva: No conflict of interest Bermejo San Jose, Fernando: No conflict of interest Van Domselaar, Manuel: No conflict of interest García, María José: Other: MJ García has received financial support for travelling and educational activities from Janssen, Pfizer, Abbvie, Takeda and Ferring. Fernandez, José Luis: No conflict of interest Garcia Alonso, Francisco Javier: I have acted as a speaker for Abbvie, Lilly and Johnson and Johnson Calvet Calvo, Xavier: Xavier Calvet has received grants for research from AbbVie Janssen, Kern and Vifor, and fees for advisory board services form Abbvie, MSD, Takeda and Vifor. He has also given lectures for Abbvie, Janssen and Takeda. Torrealba Medina, Leyanira: No conflict of interest Bastón Rey, Iria: Personal Fees: Iria Bastón Rey has received financial support for travelling and educational activities from or has served as an advisory board member for Abbvie, Johnson & Johnson, Takeda, Pfizer, Alfasigma, Ferring, Faes Farma and Otsuka Pharmaceutical and Adacyte. Pallarés-Manrique, Héctor: No conflict of interest Ber, Yolanda: Non Leo Carnerero, Eduardo: I have received grants or fees for scientific activities or as a scientific advisor for MSD, Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma, Shire Pharmaceuticals, Ferring, Dr. Falk Pharma, Lilly, Adacyte and Otsuka Pharmaceutical. Casanova, María José: María José Casanova, has received education funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk, Shire, Ferring, Galápagos and Abbvie, and research funding from Lilly. Millet, Oscar: No conflict of interest Elortza, Félix: No conflict of interest Mato, José M: No conflict of interest Tinahones, Francisco J.: No conflict of interest Chaparro, María: Grants: Pfizer, Janssen, Biogen, Abbvie, Lilly Personal Fees: Pfizer, Faes, Lilly, Abbvie, Janssen Gisbert, Javier: Grant: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Personal Fees: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma. Other: MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos/Alfasigma, Lilly, Sanofi, STADA, Teva, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, Italfarmaco, and Vifor Pharma.