Utility of measuring 6-methylmercaptopurine and 6-thioguanine nucleotide levels in managing inflammatory bowel disease patients treated with 6-mercaptopurine in a clinical practice setting

Background: Measuring levels of 6-mercaptopurine (6-MP) metabolites (6-thioguanine nucleotides [6-TGNs] and 6-methylmercaptopurine [6-MMP]) has been proposed as a method to adjust 6-MP dose to optimize therapeutic response while minimizing toxicity in patients with inflammatory bowel disease. A 6-TGN level of >230 pmol/8 × 10⁸ red blood cells (RBCs) has been reported to be associated with a higher efficacy rate, and a level of >450 pmol/8 × 10⁸ RBCs has been reported to be associated with myelotoxicity. A 6-MMP level of >5,700 pmol/8 × 10⁸ RBCs has been reported to be associated with an increased frequency of abnormal results of liver function tests (LFTs). Goals: To report our experience with 6-MMP and 6-TGN levels in a clinical practice setting. Study: Using outpatient clinic medical records, we identified 53 measurements. Indications for measurement, 6-MP dose, and subsequent adjustments were documented. Results: Indications for measurements included the following: persistent symptoms, 31 cases (58.5%); abnormal LFT results, 7 (13.2%); steroid dependency, 6 (11.3%); anemia, 4 (7.5%); and leukopenia, 2 (3.8%). Of the 31 cases with persistent symptoms, 12 had "therapeutic" 6-TGN levels and other interventions were undertaken. 6-TGN levels were "subtherapeutic" in 19. The 6-MP dose was increased, and remission was achieved in 10 cases after a mean period of 3.6 weeks. Among the cases with abnormal LFT results, 6-MMP levels were high in five and low in two. Among the steroid dependency cases, 6-TGN levels were "subtherapeutic" in five. The dose was increased and steroids were weaned in three cases. The 6-TGN level was high in one of the leukopenia cases and the 6-MP dose was decreased. 6-TGN levels were not above the "target range" in any of the anemia cases. Conclusion: Measuring levels of 6-MP metabolites may have a role in customizing 6-MP dosing. This role is not completely clear and needs to be explored in larger well-controlled studies.