Relationship between serum total bilirubin levels and primary loss of response to Infliximab therapy in Crohn’s disease patients

Crohn’s disease (CD) is a chronic inflammatory bowel disease whose global prevalence continues to rise. Infliximab (IFX) is the first-line biologic for moderate-to-severe CD, yet a high rate of loss of response (LOR) limits its long-term efficacy. Existing predictive tools are either costly or insufficient. This study aimed to evaluate the predictive value of serum total bilirubin (sTB) in combination with routine clinical and hematological parameters for IFX treatment outcomes in CD patients. We retrospectively enrolled 85 CD patients who were treated with IFX (July 2019-December 2021) and stratified them into training (n = 59) and validation (n = 26) sets. LOR was defined as failure to achieve biochemical remission (fecal calprotectin < 250 µg/g or ≥ 50% reduction from baseline) at 26 weeks post-IFX. Baseline data (demographics, laboratory values, imaging, and clinical features) were analyzed via univariate and multivariate logistic regression. A nomogram integrating significant predictors was developed and validated. Among the 85 patients, 48 (56.5%) developed LOR. Patients with LOR had significantly lower baseline sTB levels (5.86 vs. 7.88 µmol/L, P = 0.001). Multivariate analysis revealed sTB (odds ratio (OR) = 0.83, 95% confidence interval (CI): 0.64–0.99), L1 Montreal phenotype (OR = 0.23, 95% CI: 0.10–0.85), perianal lesions (OR = 3.84, 95% CI: 1.27–11.57), and elevated monocyte percentage (OR = 1.20, 95% CI: 1.00-1.49) as independent predictors of LOR. The combined model in overall patients achieved an area under the curve (AUC) of 0.80 for LOR prediction, outperforming sTB alone (AUC = 0.715). Internal validation confirmed robust performance (training AUC = 0.82; validation AUC = 0.78). Lower baseline sTB levels were associated with LOR to IFX. A simple nomograms based on sTB, L1 phenotypes, perianal lesions, and elevated monocyte percentages provide a simple tool for the identification of CD patients at high risk of LOR.