P430 The influence of persistent organ damage on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patients

Abstract

Abstract Background Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment. Methods The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model. Results The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors (Fig. 1). Additionally, alongside FC, both IFX and C-reactive protein demonstrated a significant impact on the temporal aspect of disease progression. Conclusion In this 2-year prospective real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that persistent gut damage, as mirrored by FC, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of the progression of the underlying disease. These findings underscore the imperative need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.