P0804 Morning administration of biologic therapy is associated with decreased risk of treatment failure in patients with Inflammatory Bowel Disease

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Abstract Background Biological therapy has greatly improved treatment outcomes in inflammatory bowel disease (IBD) management, but primary non-response rates of 10-30% and even higher secondary non-response rates have been reported1. Chronotherapy, which involves administering treatments in alignment with the body’s biological clock has shown promise in improving treatment efficacy across multiple diseases2,3. However, its impact on IBD management remains largely unexplored4. Here, we investigated the effect of infusion timing in IBD patients receiving infliximab or vedolizumab. Methods We conducted a retrospective observational study using electronic health records from the Mount Sinai Health System. The cohort included IBD patients with hospital encounters at least 3 months pre- and 12 months post-index date (i.e., treatment initiation) (Fig.1). Treatment failure was defined as a composite outcome of biologic discontinuation, IBD-related surgery, or hospitalisation within one year after the index date. Infusion times were categorised as AM (between 07:16 and 11:59) or PM (between 12:00 and 23:45), and the PM ratio was calculated as the percentage of PM treatments. To assess associations between timing and outcomes, we employed mixed effects logistic regression (LR) and Extreme Gradient Boosting (XGBoost) models. Models were adjusted for demographics (age, sex, race), body mass index, and clinical factors (prior IBD-related medications, hospitalization, surgeries, and concomitant immunomodulator use). Results The study included 1,211 IBD patients with 1,316 treatment courses (54.8% Crohn's disease, 45.2% ulcerative colitis; 50.1% infliximab, 49.9% vedolizumab). During the one-year follow-up period, 44.5% of cases resulted in treatment failure. 42.6% of treatments were administered AM, and 57.3% PM. The LR model showed that PM administration was associated with 10% higher odds of treatment failure (odds ratio: 1.101, 95% confidence interval: 1.009-1.201, p=0.03). The XGBoost model improved with PM ratio variable added, compared to baseline model (area under the receiver operating characteristics curve: 0.819 vs 0.623). SHapley Additive exPlanations (SHAP) analysis identified PM ratio as the most influential feature (Fig. 2A), with higher PM ratio more strongly associated with treatment failure (Fig. 2B). Conclusion Our findings suggest that infusion timing may influence biological therapy outcomes in IBD, with morning administrations being associated with better treatment outcome. These data support the potential relevance of chronotherapy in the management of IBD. References 1.Roda G, Jharap B, Neeraj N, Colombel JF. Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management. Clin Transl Gastroenterol. 2016;7(1):e135. doi:10.1038/ctg.2015.63 2.Lee Y, Field JM, Sehgal A. Circadian Rhythms, Disease and Chronotherapy. J Biol Rhythms. 2021;36(6):503-531. doi:10.1177/07487304211044301 3.Diamantopoulou Z, Gvozdenovic A, Aceto N. A new time dimension in the fight against metastasis. Trends Cell Biol. 2023;33(9):736-748. doi:10.1016/j.tcb.2023.02.002 4.Swanson GR, Biglin M, Raff H, et al. Impact of Chronotherapy on 6-Mercaptopurine Metabolites in Inflammatory Bowel Disease: A Pilot Crossover Trial. Clin Transl Gastroenterol. 2023;14(2):e00549. doi:10.14309/ctg.0000000000000549

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