P0167Variation of serum advanced glycation end products after biological therapy in Inflammatory Bowel Disease

Abstract Background Advanced glycation end products (AGEs) are formed from a non-enzymatic reaction between reducing sugars and proteins, and can either be generated in the body or introduced through diet and smoking. AGEs are suggested to promote inflammation and oxidative stress, and influence treatment resistance in IBD1. The aim of this study was to further explore the association of serum AGEs with IBD disease activity and response to biological therapy. Methods This retrospective study included IBD patients initiating biological therapy (n = 75), from a previously established cohort2. Therapy response was determined through endoscopic evaluation at week 14 for patients with ulcerative colitis (UC) (n = 36), and at week 24 for patients with Crohn’s disease (CD) (n = 39). For UC, endoscopic improvement was defined as endoscopic Mayo score (EMS) ≤ 1, with at least a 1-point decrease from baseline. For CD, endoscopic improvement was defined as simple endoscopic score for CD (SES-CD) ≤ 3 (SES-CD 0 for patients starting with SES-CD 3) and/or absence of ulceration. Serum samples were taken at baseline (w0) and after therapy outcome evaluation. Three AGEs were measured in serum using mass spectrometry: carboxymethyl-lysine (CML), N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), and pyrraline (Pyr). Results At baseline, serum MG-H1 was significantly lower in patients with UC, compared to patients with CD (p = 0.0001; Mann-Whitney test) (Fig 1B). No significant difference in baseline levels of AGEs was observed between responders and non-responders (Fig 1C). After therapy initiation, the levels of CML and MG-H1 decreased in CD, both in responders (CML: p = 0.0495; MG-H1: p = 0.0432) and non-responders (CML: p = 0.001; MG-H1: p = 0.0253) (2-way ANOVA) (Fig 1C). After receiving ustekinumab (UST), serum levels of CML significantly decreased in both responders (p = 0.0187) and non-responders (p = 0.0015) (2-way ANOVA) (Fig 2A). In CD and UC patients, serum levels of Pyr correlated positively with age (CD: p = 0.001; UC: p = 0.001) (Fig 2B). In UC patients, serum MG-H1 negatively correlated with serum C-reactive protein (p = 0.003) and the EMS (p = 0.013). In addition, serum Pyr negatively correlated with faecal calprotectin (p = 0.009) and the EMS (p = 0.015). Lastly, there was a trend towards lower levels of MG-H1 (p = 0.0765) and Pyr (p = 0.0556) in patients with EMS 3, compared to EMS 0 (Fig 2C). Conclusion Serum AGEs were not different between responders and non-responders to biological therapies, both at baseline and after treatment. We did observe differences between the serum AGEs in CD and UC patients, suggesting a different role for AGEs in both diseases. In UC patients, MG-H1 and Pyr correlated negatively with inflammatory markers, which should be further explored. References: 1. Van Der Lugt T, Weseler AR, Vrolijk MF, Opperhuizen A, Bast A. Dietary Advanced Glycation Endproducts Decrease Glucocorticoid Sensitivity In Vitro. Nutrients. 2020;12(2):441. 2. Caenepeel C, Falony G, Machiels K, et al. Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease. Gastroenterology. 2024;166(3):483-495. Conflict of interest: Ms. Vissers, Eva: No conflict of interest Wellens, Judith: No conflict of interest Caenepeel, Clara: Speaker fee: Abbvie, Alfasigma Consultancy fee: Alfasigma, Janssen 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 Verstockt, Bram: Research support from AbbVie, Biora Therapeutics, Celltrion, Landos, Pfizer, Sanofi, Sossei Heptares/Nxera and Takeda. Speaker’s fees from Abbvie, Agomab, Alfasigma, Biogen, Bristol Myers Squibb, Celltrion, Eli Lily, Falk, Ferring, Galapagos, Materia Prima, Johnson and Johnson, Pfizer, Sandoz, Takeda, Tillots Pharma, Truvion and Viatris. Consultancy fees from Abbvie, Alfasigma, Alimentiv, Anaptys Bio, Applied Strategic, Astrazeneca, Atheneum, BenevolentAI, Biora Therapeutics, Boxer Capital, Bristol Myers Squibb, Domain Therapeutics, Eli Lily, Galapagos, Guidepont, Landos, Merck, Mirador Therapeutics, Mylan, Nxera, Inotrem, Ipsos, Johnson and Johnson, Pfizer, Sandoz, Sanofi, Santa Ana Bio, Sapphire Therapeutics, Sosei Heptares, Takeda, Tillots Pharma and Viatris. Stock options Vagustim and Thethis Pharma. Vermeire, Séverine: Grant: AbbVie, Pfizer, Takeda, J&J, Galapagos Personal Fees: AbbVie - AbolerIS Pharma - AgomAb - Alimentiv - Arena Pharmaceuticals - AstraZeneca - Avaxia- BMS - Boehringer Ingelheim - Celgene - CVasThera - Dr Falk Pharma - Ferring - Galapagos - Genentech-Roche - Gilead - GSK - Hospira - Imidomics - Janssen - J&J - Lilly - Materia Prima - MiroBio - Morphic - MrMHealth - Mundipharma - MSD - Pfizer - Prodigest - Progenity - Promakhos Therapeutics - Prometheus - Robarts Clinical Trials - Second Genome - Shire - Surrozen - Takeda - Theravance - Tillots Pharma AG - Zealand Pharma - Other: AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer Inc, Galapagos, Mundipharma, Guedelha Sabino, João: Speaker’s fees: Lilly, Pfizer, Abbvie, Ferring, Falk, Takeda, Janssen, Fresenius, and Galapagos. Consultancy fees: Takeda, Pfizer, Janssen, Ferring, Fresenius, Abbvie, Galapagos, Celltrion, Pharmacosmos, and Pharmanovia. Research support: Galapagos, Viatris, and Eurogenerics. JS is supported by a Senior Clinical researcher grant from the Research foundation – Flanders.