Plasma thiopurine S-methyltransferase levels and azathioprine-related adverse events in patients with Behçet's disease.
OBJECTIVE
Thiopurine S-methyltransferase (TPMT) is the key enzyme inactivating azathioprine (AZA), an immunosuppressive agent commonly used for treating inflammatory diseases including Behçet's disease (BD), systemic lupus erythematosus (SLE) and systemic vasculitis. Low TPMT levels facilitate occurrence of AZA-related adverse effects. We investigated TPMT levels in patients with BD, compared to healthy controls and patients with SLE or systemic vasculitis.


METHODS
This cross-sectional study included 101 BD (77 using AZA), 74 SLE (35 using AZA), and 44 vasculitis (18 using AZA) patients and 101 healthy controls. Plasma TPMT levels were measured using ELISA. Student's t- and Kruskal-Wallis tests were used to compare TPMT levels according to possible risk factors. Receiver operating characteristic (ROC) analysis was used to determine whether a cut-off TPMT level could be found to predict AZA-related adverse effects.


RESULTS
Plasma TPMT levels (mean± SD ng/mL) in BD (22.80±13.81) were comparable with healthy controls (22.71±13.49), but significantly lower than in SLE group (29.37±11.39) (p<0.001). TPMT levels in 130 patients receiving AZA were similar to the rest of the group. AZA-related adverse effects were identified in only 8 patients (5 with BD and 3 with SLE). TPMT levels were significantly lower in those 8 patients (14.08±9.49 vs. 25.62±12.68) (p=0.013), besides a cut-off value for predicting adverse effects was determined for the BD group with ROC analysis (area under the curve: 0.813).


CONCLUSIONS
This is the first study to evaluate TPMT activity in a Turkish adult population. Although low plasma TPMT level is not the only factor determining AZA toxicity, a TPMT cut-off value may help to predict AZA-related adverse effects in BD.
Department of Internal Medicine, Division of Rheumatology, Koç University Hospital, Istanbul, Turkey. emmungil@mynet.com.
Hakan
H
Emmungil
Department of Public, Health Ege University School of Medicine, Izmir, Turkey.
Raika
R
Durusoy
Department of Internal Medicine, Division of Rheumatology, Acıbadem University, Istanbul, Turkey.
Melike
M
Kalfa
Department of Internal Medicine, Division of Rheumatology, Ege University School of Medicine, Izmir, Turkey.
Figen
F
Yargucu Zihni
Clinic of Internal Medicine, Division of Rheumatology, Ataturk Research and Training Hospital, Izmir, Turkey.
Mustafa
M
Özmen
Department of Internal Medicine, Division of Rheumatology, Ege University School of Medicine, Izmir, Turkey.
Gökhan
G
Keser
Department of Internal Medicine, Division of Rheumatology, Ege University School of Medicine, Izmir, Turkey.
Sercan
S
Gücenmez
Department of Internal Medicine, Division of Rheumatology, Tepecik Research and Training Hospital, Izmir, Turkey.
Zevcet
Z
Yilmaz
Department of Internal Medicine, Division of Rheumatology, Ege University School of Medicine, Izmir, Turkey.
Kenan
K
Aksu
D000328:Adult; D019540:Area Under Curve; D001379:Azathioprine / Q000009:adverse effects* / Q000378:metabolism; D001528:Behcet Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000453:epidemiology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors; D016896:Treatment Outcome; D014421:Turkey / Q000453:epidemiology
D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine