Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease

Table 2 Characteristics of included studies

Author	Location	Study design	Participants	TPMT genotypes was determined	Dose of thiopurine	ADRs and definitions
Ansari et al[14], 2008	UK	Prospective cohort	215 treated IBD patients	TPMT*3A, TPMT*3B	AZA 2 mg/kg per day	All ADRs
				TPMT*3C		BMT: WBC < 3.5 × 109 or Ne < 1.5 × 109
						H: ALT > 2 × ULN
						P: AP and amylase > 4 × ULN and supportive radiological findings
Hawwa et al[15], 2008	UK	Cross-sectional	36 treated IBD patients	TPMT*3A, TPMT*3B	AZA 1.49 mg/kg per day	BMT: WBC < 3.0 × 109 or Ne < 1.5 × 109 or PLT < 150 × 109
				TPMT*3C
Winter et al[5], 2007	UK	Cross-sectional	130 treated IBD patients	TPMT*2, TPMT*3A	AZA 1.6 mg/kg per day	All ADRs
				TPMT*3C		BMT: WBC < 3 × 109
						H: No definition
						P: No definition
Stocco et al[16], 2007	Italy	Cross-sectional	70 treated IBD patients	TPMT*2, TPMT*3A	AZA: 2 mg/kg per day	All ADRs
				TPMT*3B, TPMT*3C		BMT: WBC < 3 × 109 or PLT < 100 × 109
						H: ALT, AST or ALP > 2 × ULN
						P: AP and amylase > 2 × ULN
Palmieri et al[17], 2007	Italy	Cross-sectional	422 treated IBD patients	TPMT*3A, TPMT*3B	AZA 2-2.5 mg/kg per day	All ADRs
				TPMT*3C	or 6-MP 1-1.25 mg/kg per day	BMT: WBC < 3 × 109 or PLT < 100 × 109
						H: ALT > 2 × ULN
						P: Amylase, lipase > 2 × ULN and AP
Zelinkova et al[18], 2006	Netherlands	Cross-sectional	262 treated IBD patients	TPMT*2, TPMT*3A	AZA 2-2.5 mg/kg per day1	BMT: WBC < 3 × 109 or PLT < 100 × 109
				TPMT*3B, TPMT*3C		H: ALT > 2 × ULN
Hindorf et al[3], 2006	Sweden	Prospective cohort	60 treated IBD patients	TPMT*2, *3A, *3B	AZA 2.5 mg/kg per day	All ADRs
				TPMT*3C, *3D, *4	or 6-MP 1.25 mg/kg per day	BMT: WBC < 3 × 109 or PLT < 100 × 109
				TPMT*5, *6, *7, *8		or Ne < 1.5 × 109
				TPMT*10, *14, *15		P: No definition
Derijks et al[19], 2004	Netherlands	Prospective cohort	30 treated IBD patients	TPMT*2, TPMT*3A	6-MP 0.71 mg/kg per day	BMT: WBC < 4 × 109 or PLT < 100 × 109
				TPMT*3B, TPMT*3C
Schwab et al[20], 2002	Germany	Cross-sectional	93 treated IBD patients	TPMT*2, TPMT*3A	AZA 1.5 mg/kg per day	All ADRs
				TPMT*3B, *3C, *3D	or 1.9 mg/kg per day	BMT: WBC < 3 × 109 or PLT < 100 × 109
						H: ALT or AST > 2 × ULN
						P: Amylase, lipase > 2 × ULN and AP

¹The initial dose. White blood cells (WBC), neutrophils (Ne), and platelets (PLT) are expressed per liter; H: Hepatotoxicity; P: Pancreatitis; AP: Abdominal pain; BMT: Bone marrow toxicity; ALT: Alanine transaminase; ULN: Upper limit of normal; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase.