How I treat my inflammatory bowel disease-patients with thiopurines?

Table 1 Laboratory tests to determine risk of myelotoxicity and hepatotoxicity during initiation of thiopurine therapy

Hematologic parameters

Hemoglobin

White blood cell count

Platelet count

Hepatic parameters

Alkalic phosphatase

Gamma glutamyl transpeptidase

Alanine aminotransferase

Other parameters

Creatinine

C-reactive protein

Measuring of above mentioned parameters: Induction phase: week 0, 1, 2, 4, 8 and 12; Maintenance phase: Each 3-4 mo.

Table 2 Interpretation of metabolite levels in patients with inflammatory bowel disease treated with azathioprine or mercaptopurine

6-TGN (pmol/8 × 108 RBC)	6-MMP (pmol/8 × 108 RBC)	Non-response	Adverse event (dose-dependent)	Recommendation
<< 230	<< 5700	Non-compliance	Not expected	Gain compliance
< 230	< 5700	Non-compliance/under dosing	Not expected	Gain compliance/increase dose1
230-400	< 5700	Possible resistance to thiopurine therapy	Not expected	Increase dose1 or change therapy2
> 400	< 5700	Therapy resistance	Myelotoxicity	Change therapy2
< 230	>> 5700	Shunting	Myelotoxicity	Consider allopurinol3 or switch to TG4
< 230	> 5700	Shunting	Hepatotoxicity	Consider allopurinol, 5-ASA or switch to TG
230-400	> 5700	Possible resistance to thiopurine therapy	Hepatotoxicity	Consider allopurinol3 or 5-ASA
> 400	> 5700	Therapy resistance	Hepatotoxicity	Change therapy2
			Myelotoxicity	Decrease dose5

Therapeutic target of therapy: 6-TGN: 230-400 pmol/8 × 10⁸ RBC; 6-MMP: < 5700 pmol/8 × 10⁸ RBC.

¹AZA: Increase with 50 mg, MP: Increase with 25 mg;

²In case of thiopurine refractoriness, consider switch of therapy to non-thiopurine therapy;

³Allopurinol co-treatment with 100 mg daily requires dose-adjustment of thiopurine therapy to approximately 25%-33% of original daily dose[38,60];

⁴Treatment with thioguanine in low dose (i.e., 0.3 mg/kg) bypasses the formation of 6-MMP;

⁵In case of adverse events. 6-TGN: 6-thioguanine nucleotides; 6-MMP: 6-methylmercaptopurine; RBC: Red blood cells; <: Lower than; <<: Much lower than; >: Higher than; >>: Much higher than; AZA: Azathioprine; MP: Mercaptopurine; TG: Thioguanine; 5-ASA: 5-aminosalicylic acid (mesalazine).