Are we giving azathioprine too late? The case for early immunomodulation in inflammatory bowel disease

Figure 1 Inverted pyramid. Represents two different treatments approaches in IBD: (1) Current practice: Initially treatment with 5-ASA and antibiotics and then depends on the responsiveness scale to steroids, immunomodulators and biological agents. (2) Top-Down strategy: New tendencies. Initially aggressive treatment with early immunosuppresion and biological therapy.

Figure 2 Metabolism of azathioprine (AZA): AZA is converted to 6-mercaptopurine (6-MP). 6-MP by thiopurine methyltransferase (TPMT) and xantino oxidase (XO) in inactive metabolites, but phosphoriboxyltransferase (HPRT), inosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate synthetase (GMPS) catalize the synthesis of active 6-thioguanine nucleotides (6-TGNs).