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

Aliment Pharmacol Ther. 2003 Nov 1;18(9):917-25. doi: 10.1046/j.1365-2036.2003.01778.x.


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 ano-perineal 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 108 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.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / adverse effects*
  • Antimetabolites / adverse effects*
  • Azathioprine / adverse effects*
  • Crohn Disease / drug therapy*
  • Drug Interactions
  • Female
  • Gastrointestinal Agents / adverse effects*
  • Guanine Nucleotides / metabolism
  • Humans
  • Infliximab
  • Leukocyte Count
  • Liver Function Tests
  • Male
  • Middle Aged
  • Prospective Studies
  • Thionucleotides / metabolism
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antimetabolites
  • Gastrointestinal Agents
  • Guanine Nucleotides
  • Thionucleotides
  • 6-thioguanylic acid
  • Infliximab
  • Azathioprine