Optimizing thiopurine therapy in inflammatory bowel disease

Abstract

Despite recent advances, the therapeutic armamentarium for inflammatory bowel disease (IBD) is still limited. In addition, a step-up approach is recommended for most IBD patients. Thus, optimizing each medical therapy before switching to another drug class is the rule in clinical practice. Conventional therapies for IBD have not received the same amount of attention as biologic therapies over the last decade. However, due to their efficacy, safety, and low cost the thiopurine drugs azathioprine and 6-mercaptopurine remain the backbone of therapy for IBD. Pharmacogenomic advances and increased knowledge of their metabolism are allowing dosage optimization. Herein, after describing the pharmacogenetics and pharmacokinetics of thiopurines, we will discuss how to optimize thiopurine therapy. We will then underscore the need to take into account safety issues when optimizing thiopurine treatment.

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

“…Minimal TPMT activity can cause early, potentially life‐threatening myelosuppression in the setting of thiopurine use. Epidemiologic studies in the Caucasian population have shown a trimodal distribution of TPMT enzyme activity, with 89% having normal or high activity, 11% having intermediate activity, and 0.3% having minimal activity . The utility TPMT testing in personalizing thiopurine treatment has remained controversial in the Asian population.…”

Association Between 6-Thioguanine Nucleotides Levels and Clinical Remission in Inflammatory Disease

“…Despite the advent of anti-TNF agents, thiopurines remain the blackbone of IBD treatment. [1][2][3][4] In 2013, our therapeutic armenmatarium is still limited in IBD. Hence, optimizing available drugs is crucial when managing patients with IBD.…”

Mucosal Improvement in Patients With Moderate to Severe Postoperative Endoscopic Recurrence of Crohn’s Disease and Azathioprine Metabolite Levels

“…19 There is a major body of evidence that metabolite levels of thiopurines (e.g., 6-TGN, 6-MMPR) differ substantially between patients, a phenomenon that cannot be explained exclusively by the TPMT polymorphism, therefore requiring alternative monitoring strategies. 10,24 By now, associations of 6-TGN levels in RBC have been restricted to clinical end points in patients with IBD with partly conflicting results.…”

“…17 A potential role for metabolite monitoring in optimizing the dosing regimens of thiopurine has been considered, but it is not currently recommended in clinical practice. 18,19 To date, evidence concerning the prognostic value of thiopurine metabolite exposure is restricted to the prediction of clinical recurrence. The relationship between endoscopic improvement under azathioprine therapy and metabolite concentrations remains unknown.…”