Optimizing the switch from escalated intravenous to subcutaneous infliximab: a population
Zhigang Wang1, Marc Ferrante2,3, Séverine Vermeire2,3
1Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Importance And Objective:
It remains unclear if patients on escalated intravenous (IV) infliximab can switch to standard subcutaneous (SC) infliximab CT-P13 of 120 mg bi-weekly (Q2W) injections without losing therapeutic response. This study investigates the dose-exposure-response relationship during the IV-to-SC switching of infliximab in Crohn's disease (CD) and ulcerative colitis (UC).
Design, Setting, Participants, And Intervention(S):
Data were collected from healthy volunteers and patients with CD and UC in different Phase I studies. In patients, PK, fecal calprotectin (FC), and endoscopic remission (ER) in CD or endoscopic improvement (EI) in UC were measured during switching from 5 mg/kg IV infliximab to Q2W SC infliximab injections of 120/180/240 mg. We performed population pharmacokinetics-pharmacodynamics modeling and simulation (n = 1000 virtual patients) to evaluate FC time courses and probabilities of ER/EI post-switch.
Main Outcome(S) And Measure(S):
Fecal calprotectin levels decreased when overall infliximab exposure (not just infliximab trough concentrations) increased. Lower FC at week (w)14 was associated with increased probabilities of EI in UC, but not ER in CD. Simulations showed that the standard infliximab IV-to-SC switch at w6 further decreases FC and results in a higher probability of EI at w22/30 (54% if no switch vs 63% if switch). Virtual patients on escalated Q6W/Q8W IV maintenance regimens up to 10 mg/kg can switch to 120 mg Q2W SC infliximab without FC increases. In addition, we translated our model into a clinical software tool to guide the IV-to-SC switch of infliximab.
Conclusions And Relevance:
Patients on Q6W and Q8W IV regimens may switch to standard SC infliximab without an increase in FC.
Related Concept Videos
01:09One-Compartment Model: IV Infusion
The one-compartment model for IV infusion uses mathematical equations to describe the rate of change in drug quantity in the body. At steady-state or infusion equilibrium, the drug input...
01:18Two-Compartment Open Model: IV Bolus Administration
The disparity between drug input and the sum of drug transfer rates between...
00:59Nonlinear Pharmacokinetics: Drug Elimination for IV Bolus Injection
Following the administration of a single intravenous (IV) bolus injection, we can determine the concentration of the drug in the plasma at any given time. This calculation is achieved using a specific equation that integrates the values of Vmax and KM.
We can also...
01:15Two-Compartment Open Model: IV Infusion
The model illustrates the decrease in plasma drug concentration from the central compartment with a specific equation. It shows that under steady-state conditions, the drug's input rate...
01:25Routes of Drug Administration: Parenteral
The intravenous route (IV) of drug administration can be further categorized into two types. The bolus injection administers the entire dose rapidly, while an intravenous infusion slowly delivers smaller doses steadily.
The IV route is often...
01:19One-Compartment Open Model for IV Bolus Administration: General Considerations
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...