Optimizing thiopurine therapy in inflammatory bowel disease.
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.
Chevaux
Jean-Baptiste
JB
Department of Hepato-Gastroenterology and Inserm U954, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.
Peyrin-Biroulet
Laurent
L
Sparrow
Miles P
MP
D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008780:Methyltransferases / Q000378:metabolism
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine