Thiopurine drugs, the most commonly prescribed immunosuppressive agents used in the treatment of inflammatory bowel disease (IBD), are characterized by a narrow therapeutic window, which makes therapeutic drug monitoring (TDM) of thiopurine metabolites recommended. 6-thioguanine nucleotides (6-TGN) are considered the most active metabolites of the thiopurines and they are responsible for therapeutic efficacy and correlate with myelotoxicity. This present study aims to assess the usefulness of 6-TGN monitoring in Tunisian patients with IBD.

We performed a retrospective study including patients with IBD treated by azathioprine and underwent a TDM of 6-TGN between May 2018 and December 2023. Samples of venous blood were collected at 2 hours after medication intake. Concentrations values were determined, at the steady-state, using a technique of High-performance liquid chromatography (HPLC). Correlations between the 6-TGN concentrations and hematological parameters were assessed by Pearson's correlation coefficient.

A total of 140 patients were included (65 men/75 women). The average concentration was 386.2 ± 258.9 pmol/8 × 10 ⁸ RBCs. After an initial dose, only 49% of the patients had 6-TGN concentrations in the target range. The multiple TDM after AZA dose adjustment has shown improvement of the probability of obtaining 6-TGN concentration in the target range (69%). In our study, we demonstrated that 6-TGN concentrations were inversely correlated with hemoglobin levels, white cell, and neutrophil counts.

We have shown the usefulness of AZA TDM by determining the 6-TGN metabolite concentrations in Tunisian patients. However, this approach remains insufficient to optimize the treatment by azathioprine. Other approaches, such as genotyping patients for TPMT and NUD15 and adjusting AZA doses based on population pharmacokinetic models, appear to be essential for optimizing AZA therapy.