Pharmacogenetics in inflammatory bowel disease

As the arsenal of IBD therapies becomes more powerful, choosing a therapy that is appropriate for an individual patient requires an understanding of the goals of IBD therapy. Maximizing the efficacy of IBD-directed therapies while minimizing their toxicity remains the principal objective in developing management strategies for IBD patients. Unfortunately, for most therapeutic agents and the majority of diseases, it is not currently possible to identify patients most likely to benefit from therapy on the basis of their genetic profile, nor is it possible to identify those individuals at risk of a severe adverse reaction. However, the introduction of pharmacogenetics in the management of IBD patients has helped clinicians achieve these objectives targeted at patients receiving either 6-Mercaptopurine (6-MP) or azathioprine (AZA), both members of the thiopurine family. This research strategy involved studying the Thiopurine S-methyltransferase (TPMT) drug-metabolizing enzyme which influences the concentration of drug reaching its target (pharmacokinetics). Pharmacogenetics is the study of the role of inheritance in individual variation in drug response -with inadequate therapeutic response at one end of the spectrum and adverse drug reactions at the other. Currently, most IBD patients are treated as if they are homogenous. However patients would certainly benefit from being stratified into those that will or will not have a benefit from a therapy and further divided into those that will or will not have a toxic response to a therapy. Moreover, patients could be directed to an alternate therapy that would be more beneficial or they could avoid toxicities by being aware that the available therapeutics offer little to no benefit. The recognition and understanding of the factors influencing therapeutic response has the potential to allow clinicians and the pharmaceutical industry the ability to individualize dosing and administration regimens to maximize benefit and avoid toxicity.