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Plasma thiopurine S-methyltransferase levels and azathioprine-related adverse events in patients with Behçet's disease.
Clin Exp Rheumatol. 2015 Nov-Dec; 33(6 Suppl 94):S40-5.CE

Abstract

OBJECTIVES

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.

Authors+Show Affiliations

Department of Internal Medicine, Division of Rheumatology, Koç University Hospital, Istanbul, Turkey. emmungil@mynet.com.Department of Public, Health Ege University School of Medicine, Izmir, Turkey.Department of Internal Medicine, Division of Rheumatology, Acıbadem University, Istanbul, Turkey.Department of Internal Medicine, Division of Rheumatology, Ege University School of Medicine, Izmir, Turkey.Clinic of Internal Medicine, Division of Rheumatology, Ataturk Research and Training Hospital, Izmir, Turkey.Department of Internal Medicine, Division of Rheumatology, Ege University School of Medicine, Izmir, Turkey.Department of Internal Medicine, Division of Rheumatology, Ege University School of Medicine, Izmir, Turkey.Department of Internal Medicine, Division of Rheumatology, Tepecik Research and Training Hospital, Izmir, Turkey.Department of Internal Medicine, Division of Rheumatology, Ege University School of Medicine, Izmir, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25936353

Citation

Emmungil, Hakan, et al. "Plasma Thiopurine S-methyltransferase Levels and Azathioprine-related Adverse Events in Patients With Behçet's Disease." Clinical and Experimental Rheumatology, vol. 33, no. 6 Suppl 94, 2015, pp. S40-5.
Emmungil H, Durusoy R, Kalfa M, et al. Plasma thiopurine S-methyltransferase levels and azathioprine-related adverse events in patients with Behçet's disease. Clin Exp Rheumatol. 2015;33(6 Suppl 94):S40-5.
Emmungil, H., Durusoy, R., Kalfa, M., Yargucu Zihni, F., Özmen, M., Keser, G., Gücenmez, S., Yilmaz, Z., & Aksu, K. (2015). Plasma thiopurine S-methyltransferase levels and azathioprine-related adverse events in patients with Behçet's disease. Clinical and Experimental Rheumatology, 33(6 Suppl 94), S40-5.
Emmungil H, et al. Plasma Thiopurine S-methyltransferase Levels and Azathioprine-related Adverse Events in Patients With Behçet's Disease. Clin Exp Rheumatol. 2015 Nov-Dec;33(6 Suppl 94):S40-5. PubMed PMID: 25936353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma thiopurine S-methyltransferase levels and azathioprine-related adverse events in patients with Behçet's disease. AU - Emmungil,Hakan, AU - Durusoy,Raika, AU - Kalfa,Melike, AU - Yargucu Zihni,Figen, AU - Özmen,Mustafa, AU - Keser,Gökhan, AU - Gücenmez,Sercan, AU - Yilmaz,Zevcet, AU - Aksu,Kenan, Y1 - 2015/05/01/ PY - 2014/10/15/received PY - 2015/02/04/accepted PY - 2015/5/5/entrez PY - 2015/5/6/pubmed PY - 2016/1/15/medline SP - S40 EP - 5 JF - Clinical and experimental rheumatology JO - Clin Exp Rheumatol VL - 33 IS - 6 Suppl 94 N2 - OBJECTIVES: 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. SN - 0392-856X UR - https://www.unboundmedicine.com/medline/citation/25936353/Plasma_thiopurine_S_methyltransferase_levels_and_azathioprine_related_adverse_events_in_patients_with_Behçet's_disease_ L2 - http://www.clinexprheumatol.org/pubmed/find-pii.asp?pii=25936353 DB - PRIME DP - Unbound Medicine ER -