Anti-TNF therapy in inflammatory bowel disease Towards personalized medicine

The introduction of anti-tumor necrosis factor (TNF) biologicals, more than two decades ago has led to as a major improvement to the treatment of Inflammatory bowel disease (IBD). Nonetheless, primary non-response occurs in up to 30% of patients, and up to 50% of patients lose response over time (secondary nonresponse). To understand the mechanisms behind the phenomenon of non-response, understanding of factors that influence the pharmacokinetics and pharmacodynamics of biologicals is most important.
This thesis aimed to find patient factors associated with the pharmacokinetics of anti-TNF agents in IBD patients. On top of pharmacokinetic-based monitoring, pharmacodynamic-based monitoring might be used to optimize anti-TNF therapy. With pharmacokinetic-based monitoring, dosing is guided by measuring serum drug concentrations. As for pharmacodynamic-based monitoring, dosing is guided by changes in biomarkers that represent disease activity, such as fecal calprotectin. Also, the relationship between the anti-TNF agent infliximab and TNF concentrations is described in this thesis and this model could serve as a basis to further investigate the relationship between suppression of TNF and the response to IFX therapy. Finally, to optimize TDM, dried blood samples (DBS) could be used to measure IFX and ADL concentrations in a more timely manner. In this case, results of the measurements of DBS will be present when the patient visits the clinic and the dose can be adjusted immediately. In conclusion, the interest in personalized anti-TNF therapy in IBD patients is growing. Findings from this thesis support the use of personalized medicine for anti-TNF treated IBD patients.