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P490. How are thiopurines dosed in Crohn's disease? A novel strategy, maximum dose-titration based on the lower limit of leukocyte count and tolerability

W. Moon1, T.O. Kim2, S.J. Park1, M.I. Park1, H.H. Kim1, 1Kosin University, Department of Internal Medicine, Busan, South Korea, 2Inje University, Department of Internal Medicine, Busan, South Korea

Background

Although general guidelines have been suggested for weight-based dosing of azathioprine (2.5 mg/kg/day) for Crohn's disease (CD), substantial patients develop bone marrow suppression. Therefore, maximum optimizing dosing of AZA/6-MP without serious side effects may not only improve efficacy but also reduce the need to use additional therapy including biologic agents. 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

From 2010 to 2011, all the patients with CD treated with the maximum dose of AZA meeting both drug-tolerability and leukocytes count more than 4000/mm3 for steroid-free maintaining remission were enrolled. We evaluated the titrated maximum AZA dose and its relationship with weight.

Results

Forty-two (thirty-two, male; mean age, 31 years old) patients (remission, 34; mild, 4) were enrolled. The maximum dose of AZA meeting both drug-tolerability and leukocytes count more than 4000/mm3 for steroid-free maintaining remission was 49.1 mg/day (12.5–150 mg/day). The dose per weight was 0.87 mg/kg/day (0.17–3.06 mg/kg/day) and negatively correlated with body weight (gamma = −0.51, p = 0.01). Ten (23.8%) patients were in 0.1–0.5 mg/kg/day, twenty-three (54.8%) in 0.6–1.0 mg/kg/day, six (14.3%) in 1.1–1.5 mg/kg/day, and three (7.2%) in 1.6–3.0 mg/kg/day. Between in patients with 0.1–1.0 mg/kg/day and 1.1–3.0 mg/kg/day, significant differences of weight and height were noted (61 kg vs. 52 kg, p = 0.009 and 170 cm vs. 163 cm, p = 0.029). The mean leukocyte count was 5269/mm3.

Conclusion

Dose decision of AZA only based 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 valuable strategy in thiopurines dose-decision.