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.


OBJECTIVE
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.
Roblin
X
X
Département d'Hépato-Gastroentérologie, CHU de Grenoble, Grenoble Cedex, France.
Serre-Debeauvais
F
F
Phelip
J-M
JM
Bessard
G
G
Bonaz
B
B
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000963:Antimetabolites / Q000009:adverse effects*; D001379:Azathioprine / Q000009:adverse effects*; D003424:Crohn Disease / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects*; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D000069285:Infliximab; D007958:Leukocyte Count; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013873:Thionucleotides / Q000378:metabolism; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000963:Antimetabolites; D005765:Gastrointestinal Agents; D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; D000069285:Infliximab; D001379:Azathioprine