P0765 Insights into personalized biologic therapy with infliximab and ustekinumab: The predictive role of IL12P40 levels for mucosal healing outcomes
L Chen, X Li, X Wu, R Mao, S Hu, R FengAbstract
Background
Current consensus guidelines recommend the early initiation of biologic therapies for managing Crohn’s disease (CD). Among the first-line options, infliximab (IFX) and ustekinumab (UST) have shown significant efficacy. However, therapeutic responses vary, necessitating reliable biomarkers for personalized treatment strategies.
Methods
This retrospective study included bio-naive CD patients treated with IFX or UST at the First Affiliated Hospital of Sun Yat-sen University between May 2019 and July 2023. Clinical characteristics and endoscopic outcomes, assessed as mucosal healing (MH), were evaluated 24–32 weeks post-treatment initiation. Serum levels of 19 cytokines at both baseline and evaluation timepoint were measured. Univariate and multivariate analyses identified predictors of MH in IFX and UST cohorts. Furthermore, patients were stratified based on cytokine levels linked to treatment efficacy for IFX and UST. Comparative efficacy analysis was conducted within stratified groups.
Results
A total of 91 patients were included (IFX: 49; UST: 42). MH rates were 40.82% and 54.76% for IFX and UST, respectively, with no significant difference (P = 0.2637). In the IFX cohort, age at administration, body mass index (BMI), age at diagnosis, disease duration, CD14, and IL2 were determined to be independent predictors of MH, with the corresponding predictive model achieving an area under the curve (AUC) of 0.914 (95% confidence interval (CI): 0.876-0.953). In the UST cohort, independent predictors included gender, disease behavior, upper gastrointestinal involvement, and IL7 (AUC = 0.880, 95% CI: 0.830–0.930). Univariate analysis showed IL12P40 and IL13 were significantly associated with MH after UST treatment, though these did not persist in multivariate analysis. Post-treatment, it was observed that IL12P40 levels significantly increased in IFX responders (P = 0.0408) but decreased in UST responders (P < 0.0001). Additionally, the patients achieving MH with UST exhibited a higher baseline IL12P40 compared to those with IFX (P = 0.0052). Subsequently, Stratification by baseline IL12P40 levels (cut-off: 25.00 pg/ml) revealed higher MH rates for UST in the IL12P40-Higher group (P < 0.0001) and for IFX in the IL12P40-Lower group (P = 0.0521).
Conclusion
Baseline IL12P40 levels and treatment-associated cytokine changes are predictive of mucosal healing in CD patients treated with IFX or UST. Higher IL12P40 levels favor UST, while lower levels favor IFX, supporting cytokine profiling as a tool for personalized treatment selection in CD. These findings highlight the value of integrating biomarkers into clinical decision-making to optimize outcomes.