Population Pharmacokinetics of Subcutaneous Infliximab: A Real-World Study of Naïve and Switch Patients.

Background: Subcutaneous infliximab (SC-IFX) represents a significant advance for patients with inflammatory bowel disease (IBD) due to the possibility of home self-administration. However, at this time, there are no clear recommendations for implementing model-informed precision dosing (MIPD) in accordance with real-world clinical knowledge. Objective: The aim of the present study is to develop a population pharmacokinetic (PopPK) model for SC-IFX. Methods: A multicenter retrospective observational study was performed in adult patients (both naïve patients and those switched from intravenous administration) diagnosed with IBD. PopPK analysis was performed using NONMEM with a nonlinear mixed-effects model approach. A stepwise covariate modeling approach was implemented to identify anthropometric and clinical factors influencing SC-IFX disposition. The bootstrap method was used for internal model validation. Results: A total of 250 serum concentration samples of IFX, corresponding to 45 patients, were analyzed. A one-compartment model with first-order absorption adequately described the data. The final model included total body weight and suspected immunogenicity as covariates of clearance (CL). Suspected immunogenicity was associated with a 70.0% increase in clearance, while each kg deviation from the median weight (73 kg) modified clearance by 0.888%/kg. Conclusions: A PopPK model for SC-IFX was successfully developed and validated using European real-world data. This exploratory model establishes a foundation for future MIPD applications, offering a structured approach to initiate or transition patients to SC-IFX therapy.