| Objective 1.To explore the suitable dose of azathioprine(AZA)based on the therapeutic drug monitoring.2.To assess the role of 6-thioguanine nucleotide(6-TGN)based AZA dose adjustment in increasing clinical efficacy and reducing adverse events with Crohn's disease(CD)patients.3.To analyze the mutations ofthiopurine S-methyltransferase(TPMT)genotypes,and assess the value in AZA dose adjustment.Methods We performed a prospective observational study and collected data of CD patients in the First Affiliated Hospital of Anhui Medical University from June 2013 to April 2014,85 patients within inclusion and exclusion criteria,achieving maintenance therapy were enrolled: 14 patients were lack of the integrated data,2 patients were lost to follow up.Finally,69 patients attending maintenance therapy were analyzed.1.Demographic information,disease durations,smoking history,family history,age of diagnosis,clinical symptoms,lab tests,endoscopy,radiography and the medical treatments were recorded.TPMT was measured before AZA treatment.2.Patients were followed every week in the first month after AZA therapy,then once a month in the next 6 months,after that were followed every 3 months.These patients were followed until April 2015,drug discontinuation,switching therapy or death.6-TGN concentrations were measured very month in the first 6 months,then at each visit.In addition,6-TGN was also measured when drug adverse events occurred.3.Analyzing the total efficacy,safety and the mean dose of AZA,as well as the mutations of TPMT genotypes.Assessing the differences of the mean 6-TGNconcentrations in clinical remission group and the opposite,and that in leukopeniagroups.Comparing the rates of remission,relapse and the leukopenia in different level of 6-TGN concentrations.Results 1.86.96% patients were in complete clinical remission,13.04% had a therapeutic response.At the end of this study,92.75% patients maintained AZA treatment,only 5 patients discontinued AZA therapy.The mean AZA dose was 1.53±0.48mg/kg,40.58% patients' AZA dose were 1.5-2.0mg/kg.2.Adverse effects(AE)occurred in 30.43% patients.18.84% suffered leukopenia,9.52% suffered abnormal liver function and vomit,only one patient had a fever,nausea,alopecia and arthralgia respectively.3.The mean 6-TGN concentration in clinical remission and the clinical response was 302.06±115.85pmol/8×108 RBC vs.264.94±164.53pmol/8×108,(t=0.847,P=0.400).The total relapse rate was 13.33%,the mean 6-TGN concentration was 197.74±66.54pmol/8×108 RBC in patients who relapsedcompared to 310.26±122.38 pmol/8×108 RBC in those with sustained remission,t=-2.541,P=0.013.4.The mean 6-TGN concentration was 469.11±115.53pmol/8×108 RBC and 257.31±83.74pmol/8×108 RBC in the leukopenia and non-leukopenia groups,respectively(t=7.622,P<0.001).There was a significant negative correlation between leukocyte count and 6-TGN concentration(r=-0.326,P=0.006).5.Only one patient had a variant of heterozygous TPMT*3C mutation and suffered leukopenia.Others were identified wild-type TPMT genotype.The mutation rate was 1.4%,the specificity of predicting leukopenia was 100%,sensitivity was 7.69%.Conclusions 1.AZA in 1.5-2.0mg/kg could be the suitable dose in CD maintenance therapy.2.6-TGN based AZA dose adjustment could reduce the CD relapse rate and theoccurrence of leukopenia in AZA therapy.3.We found a low mutation rate in TPMT genotype.Although there is a high specificity in predicting leukopenia,the sensitivity is low in our research.The measurement of TPMT genotype is not recommended as a routine test in CD. |
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