Importance of 6-Thioguanine Nucleotide Metabolite Monitoring in Inflammatory Bowel Disease Patients Treated with Azathioprine

The active metabolite of azathioprine, 6-thioguanine nucleotide (6-TGN) is the main component responsible for the immunosuppressive effect in treatment of inflammatory bowel disease (IBD).

The aim of this study was to assess the correlation between the concentration of 6-thioguanine nucleotide and disease activity, azathioprine-related adverse effects and time duration of treatment in patients with inflammatory bowel disease.

Thirty-four patients were included in this study. Type of disease, gender, time duration of therapy and adverse effects were recorded. Metabolite concentration was determined by high performance liquid chromatography.

Twenty-one percent of patients have experienced an adverse effect, with leucocytopenia most commonly occurring (42.9%). More adverse effects were registered when patients were treated with azathioprine in a period of less than 3 months in comparison to the group of patients that have been under therapy between 3-12 months and more than 12 months (p˂0.05). Most of the patients that presented any adverse effect had high 6-TGN concentration (>450 pmol/8x10⁸ Er). The mean value of 6-TGN metabolite concentration in IBD patients treated with azathioprine was 437.46 pmol/8x10⁸ Er ± 198.82 pmol/8x10⁸. The time duration of azathioprine treatment did not have any significant impact on the achieved 6-TGN concentration (p>0.05).Twenty patients (58.9%) had achieved remission after therapy initiation with azathioprine.

More alertness is recommended to clinicians towards patients in the first 3 months of the therapy. Our study demonstrated that higher 6-TGN concentration is associated with azathioprine toxicity.