Background/Purpose:

Azathioprine (AZA) is an immunosuppressive agent which is widely used not only for the treatment of Behcet’s disease (BD), but also for the treatment of many systemic inflammatory diseases including systemic lupus erythematosus (SLE) and various systemic vasculitis. Thiopurine S-methyltransferase (TPMT) is a genetically moderated key enzyme involved in the metabolism of AZA. Low TPMT levels may cause a tendency for AZA-related adverse effects. In the present study, TPMT levels in patients with BD were compared with healthy controls, as well as with patients with SLE or with systemic vasculitis, as disease control groups. We investigated the relationship between TPMT levels and AZA-related adverse effects, and also whether TPMT levels were affected by AZA treatment.

Methods:

In the present cross-sectional study, 101 patients with BD (M/F: 61/40; mean age 42.15±10.33 years), 74 patients with SLE (M/F: 11/63; mean age: 39.86±11.69 years), 44 patients with systemic vasculitis (M/F: 21/23; mean age 47.09±13.36 years) and 101 healthy controls, age and sex matched with BD were included. Detailed past medical data were available for all patients. The TPMT activity in red blood cells was measured using ELISA. AZA was stopped three days before measurements in patients already receiving this drug. Data were presented as mean ± SD. Mean TPMT levels (mIU/ml) were compared with Student’s t, Mann Whitney U and Kruskal Wallis tests, and Receiver Operating Characteristic (ROC) analysis was used to determine whether TPMT could be used to predict toxicity.

Results:

Mean TPMT levels in BD (22.80±13.81) were comparable with healthy controls (22.71±13.49), but significantly lower than in patients with SLE (29.37±11.39) (p<0.001). There were 130 patients, 77 with BD, 35 with SLE, and 18 with systemic vasculitis who had used or have been currently using AZA treatment. TPMT levels were not significantly different between patients with and without AZA treatment. AZA-related adverse effects involving gastrointestinal tract, liver and bone marrow were identified in 8 out of 130 patients (5 with BD and 3 with SLE). Although the mean TPMT levels were significantly lower in patients suffering from AZA-related adverse effects (14.08±9.49) than in patients without adverse effects (25.62±12.68) (p=0.013), a cut-off value for predicting AZA-related adverse effects could not be determined with ROC analysis (Area under the curve: 0.249).

Conclusion: This was the first study evaluating TPMT activity in Turkish adult population. Despite more frequent AZA-related adverse effects in the presence of low TPMT levels, absence of a certain cut-off value for TPMT levels implicate that variation in the level of this enzyme may not be the only factor determining AZA-related adverse events. Clinical relevance of TPMT testing should further be determined with larger prospective studies.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/thiopurine-s-methyltransferase-levels-in-patients-with-behcets-disease/