Pharmacokinetic Predictor of Infection in Patients With Inflammatory Bowel Disease Treated With Intravenous and Subcutaneous Infliximab.

INTRODUCTION: Infliximab (IFX) has significantly improved outcomes for patients with inflammatory bowel disease (IBD) but also predisposes them to infection. Preinfusion trough concentration (Ctrough) is commonly used in therapeutic drug monitoring (TDM) to optimize IFX efficacy. However, reliable pharmacokinetic (PK) or clinical factors predicting infection risk in IFX-treated IBD patients have not been well established. METHODS: In a proactive TDM-based prospective cohort of IBD patients treated with intravenous (IV) or subcutaneous (SC) IFX, we collected Ctrough, anti-IFX antibody titers, demographic, clinical, and laboratory data at each 8-week visit. Cumulative IFX exposure for both IV and SC formulations, represented by the area under the concentration-time curve over 8 weeks (AUC0-8wk), was computed using a single validated population PK model. Logistic generalized linear mixed models (GLMM) with patient-level random intercepts were performed to assess associations between repeatedly measured PK parameters and infection risk. RESULTS: Among 2451 visit-infection pairs (54% Crohn's disease; 29% SC dosing), 89 infections (3.6%) occurred. Although Ctrough was not associated with infection risk, random-intercept logistic GLMM analysis revealed that corticosteroid use (OR: 3.59, 95% CI: 1.08-11.90, P=0.037), low-dose immunomodulator use (OR: 0.51, 95% CI: 0.32-0.83, P=0.007), and AUC0-8wk (OR: 1.03 per 100 mg·d/L, 95% CI: 1.01-1.05, P=0.010) were associated with infection risk. Parallel generalized estimating equations yielded nearly identical effects. A parsimonious mixed-effects model confirmed AUC0-8wk as the primary predictor. CONCLUSION: Cumulative exposure, rather than Ctrough, predicts infection risk, supporting AUC monitoring for safer IFX dosing.