PP219—Thiopurine metabolites are useful in predicting azathioprine resistance in pediatric ibd patients

Abstract

Azathioprine (AZA) is an immunosuppressive drug widely used in inflammatory bowel disease (IBD). Few data on azathioprine (AZA) therapy IBD exist for children. We evaluated whether the 6-thioguanine nucleotides (6-TGN) level predicts AZA refractoriness in children with IBD and whether children benefit an AZA dose escalation. Seventy-eight children with IBD initially treated with an AZA dose of 1.5 to 2.5 mg/kg/d were retrospectively included. The dose was adjusted based on the clinical status. 6-TGN and Me6-MPN thiopurine metabolites were determined by HPLC. The receiver operating characteristic curve and logistic regression were used to determine predictors for AZA resistance. Initially, 18 of 40 (45%) patients receiving a dose below 2 mg/kg/d and 11 of 38 (28.9%) patients receiving a dose of 2 to 2.5 mg/kg/d achieved remission. The 6-TGN level above 250 pmol/8.108 RBCs was associated with a higher remission rate, although nonsignificant. Among 35 patients with a dose escalation due to treatment failure, 12 (34.3%) achieved remission (the median 6-TGN level increased from 260 to 394 pmol/8.108 RBCs (P = 0.002)), 23 (67.6%) were AZA refractory. A 6-TGN level above 405 pmol/8.108 RBCs was the only predictor for AZA resistance (sensitivity, 78.3%; specificity, 75%; OR, 10.8 [95% CI, 2.1–55.7], P = 0.004)). Drug monitoring of thiopurine metabolites is useful to identify children with IBD resistant to AZA. Children who cannot achieve remission despite a 6-TGN level above 405 pmol/8.108 RBCs should receive alternative therapies.