Thiopurine Therapy Risk Evaluation for Inflammatory Bowel Disease Patients Using TPMT Enzyme Expression Method

Abstract

Introduction: Thiopurine drugs, what are widely used medications for the treatment of inflammatory bowel diseases (IBD), have remarcable adverse effects like myelosuppression, leading to life threatening complications (severe infection or bleeding). Thiopurine methyltransferase (TPMT) plays a significant role in the metabolism of thiopurine drugs. Low TPMT activity in body is associated with pathological thiopurine drug metabolisms, overproduction of cytotoxic metabolites and myelosuppression. Methods: A purpose of our study was to compare TPMT enzyme expression analysis in patients with ulcerative colitis (UC) and Crohn's disease (CD) who are using azathioprine therapy with patients who have not yet begun this therapy. A prospective pilot study included 20 patients (55% female n=11 and 45% male n=9) having an age ranging from 22 to 79 years. All participants where admitted to Pauls Stradins Clinical university hospital (Riga, Latvia) from January 2017 to May 2017. All included patients received standard treatment of 5-ASA, steroid or azathioprine; leucocyte level was no lower than 4 x 109/L. The expression of TPMT in each blood sample was determined using ELISA (MyBioSource, USA) method. Results: All patient was previously diagnosed with IBD and now was admitted to hospital because of IBD exacerbation. 70 % of patients (n=14) was diagnosed with UC, 30 (n=6) with CD. 75% (n=15) of patients had not previously received azathioprine. 15% (n=3) had received azathioprine therapy, but stopped using it because of negative side effects like dyspepsia, acute pancreatitis, rash or exacerbation symptoms. 10% (n=2) was still receiving azathioprine therapy. Patients TPMT expression was in the range of 1.4 to 50 U/mL. All respondents were divided into the three TPMT enzyme activity groups. Activity of TPMT was low (< 5.5 U/mL) in 10% (n=2), intermediate (5.6-15.5 U/mL) in 5% (n=1) and normal/high (>15.6 U/mL) ir 85% (n=17) of patients. Conclusion: The results of this study confirmed the important role of the TPMT enzyme activity in the therapeutic drug monitoring. 15% of examined patients had decreased TPMT activity. Further studies in combination with TPMT genotype analysis are necessary for additional evaluation of treatment risks.