Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open-label, prospective and randomised clinical trial
Résumé
BACKGROUND: Infliximab (IFX) combined with azathioprine (AZA) is more effective than IFX monotherapy in inflammatory bowel disease (IBD). AIM: To identify the AZA optimal dose that is required for efficacy when receiving combination therapy. METHODS: Patients with IBD in durable remission on combination therapy were enrolled in a 1-year, open-label, prospective trial after randomisation into three groups: AZA steady (2-2.5~mg/kg/day, n=28) vs AZA down (dose was halved 1-1.25~mg/kg/day, n=27) vs AZA stopped (n=26). Primary endpoint was failure defined as occurrence of a clinical relapse and/or any change in IBD therapy. RESULTS: Eighty-one patients were included. Five (17.9%), 3 (11.1%), and 8 (30.8%) patients experienced failure at 1~year in groups AZA steady, AZA down and AZA stopped, respectively (P=.1 across the groups). The median trough levels of IFX at inclusion were close to those measured at the end of follow-up in group AZA steady (3.65 vs 3.45~μg/mL, P=.9) and in group AZA down (3.95 vs 3.60~μg/mL, P=.5), whereas these levels dropped from 4.25 to 2.15~μg/mL (P=.02) in group AZA stopped. Four (14.3%), four (14.8%) and 11 (42.3%) patients experienced an unfavourable evolution of IFX pharmacokinetics in groups AZA steady, AZA down and AZA stopped, respectively. A threshold of 6-TGN \textless105~pmoles/8.108 RBC was associated with an unfavourable evolution of IFX pharmacokinetics. CONCLUSIONS: Under combination therapy, AZA dose reduction, but not withdrawal, appears to be as effective as continuation of AZA at full dose.