P010 Precision Dosing Tool Forecasts Trough Infliximab and Associates With Disease Status in Inflammatory Bowel...

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Immunology
• Gastroenterology

Background:

• Infliximab (IFX) pharmacokinetics (PK) exhibit significant inter- and intra-individual variability, requiring personalized dosing strategies for patients with Inflammatory Bowel Diseases (IBD).
• Current dosing regimens may not consistently achieve therapeutic infliximab levels, leading to suboptimal treatment outcomes and increased disease activity.

Purpose of the Study:

• To evaluate the performance of a Model Informed Precision Dosing (MIPD) tool in predicting trough infliximab (IFX) concentrations in IBD patients.
• To assess the association between forecasted IFX levels, clinical remission (assessed by C-reactive protein, CRP), and circulating tumor necrosis factor-alpha (TNF-α) levels.

Main Methods:

• A cohort of IBD patients on maintenance infliximab therapy were enrolled, with midcycle serum samples collected for analysis.
• Nonlinear mixed-effects modeling and Bayesian data assimilation were employed to forecast trough IFX levels using midcycle data, weight, albumin, and IFX levels.
• Deming's regression analyzed the accuracy of forecasted versus observed trough IFX levels; logistic and linear mixed-effects models examined associations with CRP and TNF-α.

Main Results:

• The MIPD tool accurately forecasted trough IFX levels, with a Deming's regression slope of 0.90 and R² of 0.87.
• Elevated forecasted trough IFX levels (>5 µg/mL) were significantly associated with CRP-based clinical remission (Odds Ratio = 21.0).
• Both CRP and TNF-α levels independently and additively correlated with decreased IFX levels, indicating increased inflammatory burden impacts drug exposure.

Conclusions:

• The developed MIPD tool demonstrates significant value in forecasting trough infliximab levels for IBD patients, enabling precision dosing.
• Serum TNF-α and CRP levels serve as reliable indicators of inflammatory burden, directly influencing infliximab exposure and treatment efficacy.