Population pharmacokinetics of infliximab in patients with inflammatory bowel disease: potential implications for dosing in clinical practiceBuurman, D. J., Maurer, J. M., Keizer, R. J., Kosterink, J. G. W. & Dijkstra, G., Sep-2015, In : Alimentary Pharmacology & Therapeutics. 42, 5, p. 529-539 11 p.
Research output: Contribution to journal › Article › Academic › peer-review
- Pharmacotherapy and Pharmaceutical Care
- Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
- Targeted Gynaecologic Oncology (TARGON)
- Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
- Translational Immunology Groningen (TRIGR)
BackgroundInfliximab (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 3.0mg/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.
AimsTo 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.
MethodsAn 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.
ResultsIndividual 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 3.0mg/L can be achieved by increasing dosing intervals from 8 to 12weeks combined with a dose increase. This results in a reduction of 33% in concomitant costs.
ConclusionsIn IBD patients without ATI, trough level dosing based on longer intervals canreduce IFX therapy-related visits to the hospital with one-third. Trough level based dose intensification should always be justified by disease activity parameters.
|Number of pages||11|
|Journal||Alimentary Pharmacology & Therapeutics|
|Publication status||Published - Sep-2015|
- SCHEDULED MAINTENANCE TREATMENT, CROHNS-DISEASE, SERUM INFLIXIMAB, ULCERATIVE-COLITIS, DOSE INTENSIFICATION, TROUGH LEVELS, ACCENT-I, ANTIBODIES, EFFICACY, COHORT