Population pharmacokinetics of infliximab in patients with inflammatory bowel disease: potential implications for dosing in clinical practice.

Abstract

BACKGROUND:

Infliximab (IFX) is effective in the treatment of inflammatory bowel diseases (IBD). Currently, IFX is administered at fixed doses and intervals; however, costs are high and optimisation is necessary. Several publications indicate that IFX should be dosed on trough levels ≥3.0 mg/L. For optimising IFX dosing, the use of a pharmacokinetic model is important. Population pharmacokinetics of IFX have been described earlier; however, these models were not used for dose optimising.

AIMS:

To develop a pharmacokinetic model for IFX in IBD patients that can be used for dose-optimisation of IFX and to predict serum trough levels in this population.

METHODS:

An observational retrospective study was performed in 42 IFX-treated IBD patients. Serum samples were drawn before infusion at T = 0, 2, 6, 14, 22 and 54 weeks and analysed for IFX and antibodies against IFX (ATI). Relevant covariates were recorded and a population pharmacokinetic model was developed.

RESULTS:

Individual plots created using the final model showed good correspondence between observed and model predicted values. Serum levels were influenced by ATI, disease activity, sex and albumin. Our results show that in patients without ATI target trough levels ≥3.0 mg/L can be achieved by increasing dosing intervals from 8 to 12 weeks combined with a dose increase. This results in a reduction of 33% in concomitant costs.

CONCLUSIONS:

In IBD patients without ATI, trough level dosing based on longer intervals can reduce IFX therapy-related visits to the hospital with one-third. Trough level based dose intensification should always be justified by disease activity parameters.

• Authors: D J Buurman, J M Maurer, R J Keizer, J G W Kosterink, G Dijkstra
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 42 Issue 5 Pg. 529-39 (Sep 2015) ISSN: 1365-2036 [Electronic] England
• PMID: 26113313 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Gastrointestinal Agents
• Serum Albumin
• Infliximab

Topics

• Adult
• Aged
• Aged, 80 and over
• Female
• Gastrointestinal Agents (administration & dosage, immunology, pharmacokinetics, therapeutic use)
• Humans
• Inflammatory Bowel Diseases (drug therapy)
• Infliximab (administration & dosage, immunology, pharmacokinetics, therapeutic use)
• Male
• Middle Aged
• Monte Carlo Method
• Retrospective Studies
• Serum Albumin
• Severity of Illness Index
• Sex Factors