Personalised therapy during preconception and gestation in SLE: usefulness of 6-mercaptopurine metabolite levelswith azathioprine.

Although azathioprine (AZA) is the immunosuppressive of choice in SLE pregnancies, no one has evaluated 6-mercaptopurine (6-MP) metabolite levels in this population. Even outside pregnancy, the use of metabolite testing has not been widely applied in SLE.1 AZA is a prodrug that is cleaved to 6-MP, which is converted to the active nucleotides 6-thioguanine (6-TG) and via the enzyme thiopurine methyltransferase (TPMT) to 6-methylmercaptopurine (6-MMP) (figure 1).1 Studies in inflammatory bowel diseases (IBD) established the therapeutic range for 6-TG concentrations between 235 and 450 pmol/8×108 red blood cells (RBC), as higher concentrations are associated with higher risk of myelotoxicity without increased efficacy.1 6-MMP levels >5700 pmol/8×108 RBC are associated with a higher risk of hepatotoxicity.1 Additionally, a subgroup of patients resistant to AZA shunts 6-MP towards the overproduction of 6-MMP, which is reflected in an inability to achieve therapeutic 6-TG levels despite dose escalation.1 In one study, 31% of patients on AZA were identified as ‘shunters’.2 Figure 1 Azathioprine metabolism. AZA, azathioprine; 6-MP, 6-mercaptopurine; 6-TG, 6-thioguanine; 6-MMP, 6-methylmercaptopurine; TPMT, thiopurine methyltransferase. Identifying patients as non-adherent, treatment-refractory or undertreated, as well as identifying drug toxicity, could improve the efficacy and safety of clinical decision-making. As pregnancy is a particularly critical period to optimise disease control and minimise drug toxicity, we evaluated …