P1045 Treat-smart study: Leveraging individual inflammatory markers for personalized therapy in patients with IBD
M Medhat, Y N Ramadan, M Hashem, A Doaa, Z Nariman, H F Hetta,Abstract
Background
Diverse patient responses to treatment challenge the management of inflammatory bowel disease (IBD). This study aims to evaluate if there are differences in the inflammatory mediators among IBD patients and the treatment outcome concerning these variations.
Methods
This study was conducted in the IBD clinic at AL-Rajhi Hospital, Assiut University. The concentrations of TNF-α and IL-12/23 (p40) were measured in IBD patients and healthy controls using enzyme-linked immunosorbent assay (ELISA) technique. In IBD patients, marker levels were assessed before and after induction of biological therapy to evaluate changes in their levels. Biological therapies were prescribed according to the treatment protocols of the funding entities (such as health insurance). The investigators did not know the levels of inflammatory markers at the time of treatment prescription.
Results
From May 23, 2023, to July 16, 2024,18 IBD patients were enrolled in this study. Half of the study population were males with a median age of 27 years. The cohort included 16 patients with Ulcerative Colitis and 2 with Crohn’s disease, as shown in table 1. Before enrollment, 9 patients had failed to achieve remission on conventional therapy, and 9 had also failed on both conventional and first-line biological therapies. The analysis of the inflammatory markers at baseline showed significant variation among patients. Third of the patients (6 out of 18) showed only elevation in the TNF- α, one patient had only elevated IL 12/23, and the rest had combined elevation of both markers. Among patients with TNF-α as the predominant pathway, remission was achieved in all patients given anti-TNF-α therapy (5 out of 6 patients). In contrast, one patient with IL12/23–dominant group failed to achieve remission after receiving Ustekinumab. In the same context, another patient with elevated IL-12/23 alone failed to respond after receiving anti-TNF-α treatment. Patients with elevated levels of both TNF-α and IL 12/23 (11 patients) exhibited mixed responses. Among those treated with anti-TNF-α, only 1 achieved remission, while 7 experienced treatment failure. Using Ustekinumab in this subgroup led to remission in only 1 out of 3 cases, as shown in figure 1.
Conclusion
These results showed that treatment response is significantly influenced by the predominant inflammatory pathway expressed in patients with IBD. Specifically, patients with TNF-α dominant pathway showed a high remission rate with anti-TNF-α therapy. Conversely, non-specific treatments were less effective, emphasizing the importance of targeted therapy. Patients with dual-marker elevation may have better responses by combo therapy or JAK inhibitors. These results may pave the way for tailored treatment for IBD patients.