Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection

Area of Science:

• Pharmacology
• Immunology
• Rheumatology

Background:

• Biologic therapies like infliximab can induce antidrug antibodies (ADAs).
• ADAs are linked to reduced drug efficacy, faster clearance, and infusion reactions.
• Predicting ADA formation is crucial for optimizing treatment outcomes.

Purpose of the Study:

• To identify predictors of baseline infliximab clearance.
• To identify predictors of early antidrug antibody formation.
• To inform clinical practice for infliximab dosing and ADA management.

Main Methods:

• Developed pharmacokinetic and pharmacokinetic/pharmacodynamic models for infliximab.
• Utilized data from 21,178 observations across 859 patients in the PLANETRA and PLANETAS studies.
• Analyzed predictors including body weight, C-reactive protein, albumin, and serum glucose.

Main Results:

• Infliximab pharmacokinetics were described by a 2-compartment model with a mean baseline clearance of 0.26 L/day.
• Elevated serum glucose, increased body weight, CRP, and decreased albumin predicted higher infliximab clearance.
• In rheumatoid arthritis, baseline clearance and body weight predicted early ADA detection.

Conclusions:

• Increased serum glucose is a novel independent predictor of baseline infliximab clearance.
• Baseline infliximab clearance and body weight are key predictors of early ADA formation.
• Incorporating baseline clearance estimates can guide infliximab dosing and ADA prophylaxis.