How Should Azathioprine Be Dosed in Crohn's Disease? A Novel Strategy of Maximum Dose-titration Based on the Lower Limit of Leukocyte Count and Tolerability / 대한소화기학회지

ABSTRACT

BACKGROUND/AIMS: Although general guidelines have suggested weight-based dosing of azathioprine (AZA, 2.5 mg/kg/day) for Crohn's disease (CD), a substantial number of patients develop bone marrow suppression. The aim of this study was to evaluate the maximum dose of AZA not based on weight but titrated according to the lower limit of leukocyte count for maintaining remission in patients with CD. METHODS: Among a total of seventy-eight patients with CD, who had been followed-up at Kosin University Gospel Hospital (Busan, Korea) from 2010 to 2011, those treated with the maximum dose of AZA meeting both drug-tolerability and leukocytes count of more than 4,000/mm3 for steroid-free maintaining remission were enrolled. The titrated maximum AZA dose and its relationship with weight were evaluated. RESULTS: A total of 42 patients (male, 32 patients; mean age, 31 years) were enrolled. The maximum dose of AZA was 49.1 mg/day. The dose per weight was 0.87 mg/kg/day and negatively correlated with body weight (gamma=-0.51, p=0.01) and BMI (gamma=-0.33, p=0.034). AZA dose per weight in the below 40 years old group was significantly higher than that in the above 40 years old group (p=0.039). CONCLUSIONS: Dose decision of AZA based only on weight could put the patients to inappropriately low or high dose resulting in need of additional therapy or serious side effect, respectively. Therefore, the maximum dose-titration based on the lower limit of leukocyte count and tolerability is a novel and a valuable strategy in deciding the dose of thiopurines.