Azathioprine-induced Adverse Effects And Risk Factors For Their Occurrence

BACKGROUND:Azathioprine is the most frequently used immunosuppressant drug for maintaining remission in inflammatory bowel diseases(IBD)in China,and it is unlikely to be replaced by any other drugs in the following decades for Chinese patients.Inevitable adverse effects,however,leading to limitation of AZA use.Characteristics of azathioprine-induced adverse effects among Chinese patients have barely been summarized or generalized before,neither risk factors for AZA-induced adverse effects have been evaluated.AIM:This 20-year retrospective cohort study aims to evaluate the type,frequency,course and outcome of AZA-induced adverse effects in eastern Chinese IBD patients.To identify predictive factors of AZA-induced adverse events.To find out suitable suggestion for Chinese doctors to handle AZA-induced AEs either before or after their occurrence.PATIENTS AND METHODS:All the patients initiated AZA during 1994 to 2015 in our IBD center were enrolled in this study.Clinical and demographic data were gathered from database of our hospital.Chi-squared test and Logistic regression models were performed to analyze the statistics.RESULTS:Adverse effects were complained by 24.6%patients at a median of 1.23 month(IQR 0.68-5.18 months)after first AZA prescription.Leukopenia,occurring in 15.2%patients,became the most common and most dangerous AE.All of the AEs were cured after cessation or reduction of AZA.Female and initiation dose>lmg kg-1 d-1 seemed to raise the possibility of AEs.While Female,NUDT15R139C mutation significantly increased the risk of Leukopenia.CONCLUSIONS:Leukopenia is the most frequent AE among Chinese patient.Initiation over than 1mg/kg-1d-1 could raise the risk of AE.Female is a risk factor for developing AZA-induced adverse effects,while female and NUDT15 mutation carriers are predictive factors for leukopenia.We highly recommend to measure NUDT15R139C genotype before AZA prescription.Heterozygous mutation of NUDT15R139C is more likely to suffer leukopenia with higher grade than Homozygous mutation and wild type.Hair loss may be a sign for severe leukopenia.