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

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).