In recent years, with the increasing availability of
biologic therapies and due to safety concerns, the role of thiopurines in the management of
inflammatory bowel disease has been questioned. While acknowledging that the benefit/risk ratio of
biologic therapies is very high, they are expensive and are not required by a majority of patients. Therefore, thiopurines do retain an important role as
steroid-sparing and maintenance agents when used as monotherapy, and in combination
therapy with biologics due to their clinical and pharmacokinetic optimization of anti-
tumor necrosis factor agents in particular. Safety concerns with thiopurines are real but also relatively rare, and with careful pre-treatment screening and ongoing monitoring
thiopurine benefits outweigh risks in the majority of appropriately selected patients. Measurement of newer pharmacogenomic markers such as
nudix hydrolase 15 (NUDT15), when combined with knowledge of existing known mutations (e.g.,
thiopurine S-methyltransferase-TPMT), will hopefully minimize the risk of potentially life-threatening
leukopenia by allowing for pre-treatment dosing stratification. Further optimization of
thiopurine dosing via measurement of
thiopurine metabolites should be performed routinely and is superior to weight-based dosing. The association of thiopurines with
malignancies including
lymphoproliferative disorders needs to be recognized in all patients and individualized in each patient. The decrease in
lymphoma risk after
thiopurine cessation provides an incentive for
thiopurine de-escalation in appropriate patients after a period of prolonged deep remission. This review will summarize the current role of thiopurines in
inflammatory bowel disease management and provide recommendations for commencing and monitoring
therapy, and when to consider de-escalation.