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SAT0202 Identification of thiopurine methyltransferase (TPMT) activity can predict azathioprine-related hematotoxicity in the maintenance therapy of systemic lupus erythematosus patients

Objectives To investigate the azathioprine-related adverse drug reactions (ARDs) in the maintenance therapy of systemic lupus erythematosus (SLE) patients and the relationship between thiopurine methyltransferase (TPMT) activity and these ARDs. Methods TPMT activity of 250 patients with SLE and AZA maintain therapy was determined by high performance liquid chromatography (HPLC). The ARDs of AZA were followed up. Results The most common ARDs was hematotoxicity (8.4%), followed by gastrointestinal reactions (7.6%), hepatotoxicity (3.2%), alopecia (2%). 1 case suffered acute pancreatitis. Leukopenia (8.0%) and thrombocytopenia (3.6%) were the most frequent ARDs of hematotoxicity. The mean TPMT activity was 12.36±7.07U/mlRBC (range 1.72-30.03U/ml RBC). The activity of TPMT showed a normal skewness distribution.The mean TPMT activity of cases who experienced hematotoxicity and alopecia was much lower than the cases who never experienced these ARDs (P<0.001). No significan difference between the mean TPMT value of cases with hepatotoxicity or gastrointestinal reactionsand the control mean (P>0.05) was seen. The cases with low TPMT activity tend to suffer hematotoxicity at the low dose of AZA (50mg/d). Conclusions The most common AZA related -ARDs was hemototoxicity in the maintain therapy of SLE. This study demonstrates that AZA-induced hematotoxicity is related to the reduced TPMT activity. The cases with low TPMT activity tend to experience hematotoxicity at the low dose of AZA. Azathioprine dose selection based on TPMT activity testing may minimize the risk of hemototoxicity. Disclosure of Interest None Declared