Drug interaction between infliximab and azathioprine in patients with Crohn's disease

Background: A drug interaction has been observed between infliximab and methotrexate in rheumatoid arthritis. Aim: To look for an interaction between infliximab and azathioprine in Crohn's disease patients using the active metabolites of azathioprine: 6-tioguanine nucleotides. Methods: Patients receiving azathioprine who required infliximab for ileo-colonic or ano-perineal Crohn's disease were recruited prospectively. 6-tioguanine nucleotide levels were evaluated before infusion, within 1-3 weeks after the first infusion and 3 months after the first infusion. The clinical outcome was evaluated by the Harvey-Bradshaw index or the closure of anoperineal fistulas. Results: Thirty-two patients were included (17 received one infusion and 15 received three infusions). The mean 6-tioguanine nucleotide level was comparable before and 3 months after the first infusion, but a significant increase was observed within 1-3 weeks after the first infusion (P < 0.001). In parallel, a significant decrease in leucocyte count and increase in mean corpuscular volume were observed; these modifications were normalized 3 months after infusion. An increase in 6-tioguanine nucleotide level of greater than 400 pmol/8 x 10(8) erythrocytes was strongly related to good tolerance and a favourable response to infliximab, with a predictive value of 100%. Conclusions: This prospective study provides evidence for a drug interaction between azathioprine and infliximab.