OP13Biomarker-informed therapy guidance improved clinical outcomes of anti-tumour necrosis factor treatment in patients with inflammatory bowel disease in a multi-centre, randomized, controlled, open-label, prospective clinical trial (GUIDE-IBD)

Abstract Background Anti-Tumour Necrosis Factor (TNF) therapies are a cornerstone in the treatment of inflammatory bowel disease (IBD), yet therapy responses vary widely among patients. Despite extensive biomarker discovery efforts, the clinical utility of defined molecular marker sets remains largely unexplored. The GUIDE-IBD trial was designed to assess the efficacy of biomarker-informed therapy decisions by comparing guidance through a molecular therapy board to standard medical care in active IBD patients initiating anti-TNF therapy. Methods A randomized controlled trial was conducted at three German university hospitals (DRKS00032030). Adults with Crohn’s disease (CD) or ulcerative colitis (UC) with an indication for first-time infliximab therapy were randomized to “molecular medicine care” (MMC) or “best care” (BC), stratified by diagnosis, centre and baseline corticosteroid use. Molecular assessments (at baseline, weeks 2, 6, 14, and 26), including mRNA-based biomarkers from blood and biopsies, were processed real-time and provided as a principal-component analysis along with pharmacometrics modelling. Molecular reports were provided for the MMC group at weeks 2, 14, 26 and 52; BC data were not disclosed. Primary outcome was Comprehensive Disease Control (CDC) at week 52 (clinical remission (CDAI 150, Partial Mayo 2), endoscopic remission (SES-CD ≤4 ≤2 in ileal CD, MES ≤1), and biochemical normalization (CRP 5 mg/L, faecal calprotectin 250 mg/g) ). A logistic regression model with adjustment for the covariates used for randomization and gender was used to test superiority of the MMC arm compared to BC and to estimate odds ratios and adjusted endpoint proportions. Results 103 patients were randomized between 4th February 2021 and 18th January 2024 and included in the modified intention-to-treat analysis. At week 52, CDC was significantly more frequent in the MMC group (22 of 48 patients, adjusted proportion 43%) compared to the BC group (14 of 55, adjusted proportion 23%), with an odds ratio of 2. 53 (95%-CI: 1. 09-5. 86, p = 0. 031). All secondary outcomes were in favour of the MMC arm, such as steroid free remission, clinical remission and endoscopic remission, while difference between both arms was only significant for steroid free remission. More therapy switches occurred in the MMC arm (48% vs. 29%) and dose adjustments were also more frequent in the MMC arm (48% vs. 35%). Conclusion Biomarker-informed guidance significantly improved therapy outcomes, with a higher proportion of patients achieving CDC compared to standard “best care” in the context of anti-TNF therapy. These findings support the integration of molecular medicine approaches in therapy boards to optimize treatment strategies in IBD. References: 1. Mishra N, Aden K, Blase JI, et al; SYSCID Consortium. Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease. Genome Med. 2022;14 (1): 110. doi: 10. 1186/s13073-022-01112-z 2. Schräpel C, Kovar L, Selzer D, et al. External model performance evaluation of twelve infliximab population pharmacokinetic models in patients with inflammatory bowel disease. Pharmaceutics. 2021;13 (9): 1368. doi: 10. 3390/pharmaceutics13091368 3. Schreiber S, Aden K, Tran F, Rosenstiel P. Rise of precision medicine: can it deliver on its promise in IBD? Gut. Published online October 6, 2025. doi: 10. 1136/gutjnl-2023-330000 4. Schreiber S, Feagan BG, Louis E, et al. Distinct trajectories of symptomatic response in ulcerative colitis during filgotinib therapy: a post hoc analysis from the SELECTION study. United European Gastroenterol J. 2024;12 (9): 1243-1255. doi: 10. 1002/ueg2. 12686 Conflict of interest: Tran, Florian: Grant: Sanofi/Regeneron Personal Fees/Speaker’s fees: Abbvie, Bristol-Myers-Squibb, Celltrion Healthcare, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, J&J, Sanofi, Takeda Consulting honoraria: AbbVie, J&J, Takeda Aden, Konrad: Personal Fees: Lecture fee: Takeda, Janssen, Lilly, Abbvie Consulting fee: Takeda, Jannsen, Lilly, Guidepoint P. Bernardes, Joana: I have no conflict of interest to declare Imm, Charlot: No conflicts Kovar, Christina: C. K. is an employee of Pharmetheus AB. Rüdesheim, Simeon: No conflict of interest Dankowski, Theresa: No conflict of interest Florea, Marina: Takeda Pharma Vertrieb GmbH, Abbvie, Dr. Falk Pharma, Galapagos Biopharma Germany GmbH/Alfasigma, Janssen Pharmaceutica Stallbaum, Franziska: ECCO Grant 2025 (PROP-2580) DFG Clinician Scientist Grant 2024 (#493624519) Speakers Honorary: Abbvie (2023, 2024) Nikolaus, Susanna: No conflict of interest Szymczak, Silke: grant GUIDE-IBD from the German Ministry of Education and Research (BMBF, 031L0188A) Hofmann, Ute: none Lehr, Thorsten: No conflict of interest Schwab, Matthias: Support (Institution) from Robert Bosch Stiftung Stuttgart, Robert Bosch GmbH, CORAT Therapeutics, HepaRegeniX GmbH, Boehringer Ingelheim, Agena Bioscience. Personal honoraria for lectures from CED Service GmbH for expert testimony from Research Impact Fund Committee (RIF), Research Grant Council (RCG), Hong Kong, German Federal Ministry of ederal Ministry of Research, Technology and Space (BMFTR) for editorial tasks from Pharmacogenetics & Genomics, Editor-in-Chief, and Drug Research Editor-in-Chief. Participation on data safety monitoring boards without financial compensation for VoriconazolAD-trial and Atticus Trial. Dempfle, Astrid: No conflicts Huber, Samuel: SH received personal compensation and fees for lectures and consultations as well as travel costs from Janssen Cilag, AbbVie, Ferring, Falk Foundation, Galapagos, Lilly, Bristol-Myers Squibb, and Ardeypharm GmbH Wiestler, Miriam: Financial compensation for lectures, advisory boards, other medical-scientific services by: AbbVie, Alfasigma, CED Service, Dr. Falk Pharma, FomF Forum für medizinische Fortbildung, FORUM Institut für Management GmbH, Johnson & Johnson, Lilly Deutschland GmbH, Pfizer, Takeda Pharma. Seidler, Ursula: No conflict of interest Rosenstiel, Philip: stock ownership Gerion Schreiber, Stefan Wolfgang: Grant: Sanofi/Regeneron Personal Fees: Speaker’s fees: Abbvie, Bristol-Myers-Squibb, Celltrion Healthcare, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, J & J, Sanofi, Takeda Consulting honoraria: AbbVie, J & J, Takeda Non-financial Support: Sanofi for statistical analysis