Concomitant 5-aminosalicylic acid treatment does not affect 6-thioguanine nucleotide levels in patients with inflammatory bowel disease on thiopurines

Background There are conflicting data as to whether co-treatment with 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) under azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy may influence 6-thioguanine nucleotide (6-TGN) concentrations, and whether this combination puts patients at risk of side-effects. The aim of the study was to determine 6-TGN levels in patients treated with AZA/6-MP, either alone or in combination with 5-ASA. Methods Available blood samples from patients treated with AZA or 6-MP were retrieved from the Swiss IBD Cohort Study (SIBDCS). The eligible individuals were divided into 2 groups: those with vs. without 5-ASA co-medication. Levels of 6-TGN and 6-methylmercaptopurine ribonucleotides (6-MMPR) were determined and compared. Potential confounders were compared between the groups, and also evaluated as potential predictors for a multivariate regression model. Results Of the 110 patients enrolled in this analysis, 40 received concomitant 5-ASA at the time of blood sampling. The median 6-TGN levels in patients with vs. those without 5-ASA co-treatment were 261 and 257 pmol/8x108 erythrocytes, respectively (P=0.97). Likewise, there were no significant differences in 6-MMPR levels (P=0.79). Through multivariate analysis, 6-TGN levels were found to be significantly higher in non-smokers, patients without prior surgery, and those without signs of stress-hyperarousal. Conclusions Blood concentrations of 6-TGN and 6-MMPR did not differ between patients with vs. those without 5-ASA co-treatment. Our data warrant neither more frequent lab monitoring nor dose adaptation of AZA in patients receiving concomitant 5-ASA treatment.

Automated summary

There is conflicting data on whether co-treatment with 5-aminosalicylic acid (5-ASA) in inflammatory bowel disease patients under azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy may affect 6-thioguanine nucleotide (6-TGN) concentrations and put patients at risk of side effects. This study aimed to determine 6-TGN levels in patients treated with AZA/6-MP, either alone or in combination with 5-ASA. The results showed that blood concentrations of 6-TGN and 6-methylmercaptopurine ribonucleotides (6-MMPR) did not differ between patients with and without 5-ASA co-treatment.