6-Mercaptopurine (6-MP) and its pro-drug azathioprine have proven efficacy in the maintenance of disease remission in children with steroid-dependent Crohn's disease. However, not all patients respond effectively to therapy, while others are predisposed to drug-induced toxicity; thereby, suggesting that inherent differences in anti-metabolite metabolism may influence clinical responsiveness to therapy. Although genomic (TPMT) and drug metabolite monitoring have been available for greater than a decade, there is more debate than consensus on their application in clinical practice, primarily due to the lack of controlled clinical trials.Nevertheless, patients with a homozygous recessive TPMT genotype should not be considered candidates for anti-metabolite therapy. Physicians treating patients with a heterozygote genotype should consider a more moderate dosing strategy, while carefully monitoring for potential antimetabolite-induced cytotoxicity. In these patients, 6-MP-metabolite testing may help clinicians monitor immunosuppression and decrease the risk of toxicity. Future prospective clinical trials are necessary in order to develop a therapeutic window of clinical efficacy and toxicity based on the measurement of these drug metabolites.
ASJC Scopus subject areas
- General Medicine