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Cited 34 time in webofscience Cited 35 time in scopus
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Genotype-based Treatment With Thiopurine Reduces Incidence of Myelosuppression in Patients With Inflammatory Bowel Diseases

Authors
Chang, Ji YoungPark, Soo JungJung, Eun SukJung, Sung-AeMoon, Chang MoChun, JaeyoungPark, Jae JunKim, Eun SunPark, YehyunKim, Tae-IlKim, Won HoCheon, Jae Hee
Issue Date
Aug-2020
Publisher
ELSEVIER SCIENCE INC
Keywords
Immune Modulator; Adverse Drug Reaction; Genetic Risk Factor; Metabolism
Citation
Clinical Gastroenterology and Hepatology, v.18, no.9, pp 2010 - 2018.e2
Indexed
SCIE
SCOPUS
Journal Title
Clinical Gastroenterology and Hepatology
Volume
18
Number
9
Start Page
2010
End Page
2018.e2
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/33655
DOI
10.1016/j.cgh.2019.08.034
ISSN
1542-3565
1542-7714
Abstract
BACKGROUND & AIMS: Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pretreatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments. METHODS: We performed a multicenter, prospective study of patients with IBD at 5 tertiary medical centers in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2-2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/mL, levels of hemoglobin 10 g/dL, or platelet counts below 100 K/mL. RESULTS: Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (P=.005). A multivariate analysis revealed that body mass indices above 21 kg/m2 (hazard ratio=HR], 0.43; 95% CI, 0.22-0.81; P=.009), pretreatment genotype analysis (HR, 0.37; 95% CI, 0.18-0.77; P=.008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19-0.59; P<.001) independently decreased risk of myelosuppression. Pretreatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions. CONCLUSIONS: In a randomized controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leukopenia significantly reduced the proportion of patients with myelosuppression during treatment. ClinicalTrials.gov no: NCT03719118.
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Kim, Eun Sun
Anam Hospital (Department of Gastroenterology and Hepatology, Anam Hospital)
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