TPMT testing before azathioprine therapy?
Azathioprine has been in use for decades as an immunosuppressant treatment for various autoimmune diseases. It is a prodrug of mercaptopurine, a substance that is subsequently metabolised by several alternative pathways, one of which involves the enzyme thiopurine methyltransferase (TPMT). Some people have deficiency of TPMT because of genetic mutations. This has been widely said to occur in around 3 in 1,000 individuals;1 however, studies in recent years have suggested a prevalence of up to 6 in 1,000.2,3 These people are at great risk of developing severe, potentially life-threatening bone marrow toxicity when treated with conventional doses of azathioprine or mercaptopurine. It is possible to test patients for TPMT activity before starting treatment with these drugs. Here we review the evidence about such testing, and discuss whether it should be used for patients being considered for azathioprine therapy.
D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced* / Q000517:prevention & control; D004796:Clinical Enzyme Tests / Q000191:economics / Q000379:methods; D003362:Cost-Benefit Analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008780:Methyltransferases / Q000172:deficiency*
D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine