Looser Rahel, Doulberis Michael, Rossel Jean-Benoit, Franc Yannick, Müller Daniel, Biedermann Luc, Rogler Gerhard
Department of Gastroenterology and Hepatology, University Hospital Zurich (USZ), and Zurich University, Zurich, Switzerland (Rahel Looser, Michael Doulberis, Luc Biedermann, Gerhard Rogler).
Gastroklinik, Private Gastroenterological Practice, Horgen, Switzerland (Michael Doulberis).
Ann Gastroenterol. 2023 Nov-Dec;36(6):637-645. doi: 10.20524/aog.2023.0832. Epub 2023 Nov 3.
There are conflicting data as to whether co-treatment with 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) under azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy may influence 6-thioguanine nucleotide (6-TGN) concentrations, and whether this combination puts patients at risk of side-effects. The aim of the study was to determine 6-TGN levels in patients treated with AZA/6-MP, either alone or in combination with 5-ASA.
Available blood samples from patients treated with AZA or 6-MP were retrieved from the Swiss IBD Cohort Study (SIBDCS). The eligible individuals were divided into 2 groups: those with vs. without 5-ASA co-medication. Levels of 6-TGN and 6-methylmercaptopurine ribonucleotides (6-MMPR) were determined and compared. Potential confounders were compared between the groups, and also evaluated as potential predictors for a multivariate regression model.
Of the 110 patients enrolled in this analysis, 40 received concomitant 5-ASA at the time of blood sampling. The median 6-TGN levels in patients with vs. those without 5-ASA co-treatment were 261 and 257 pmol/8×10 erythrocytes, respectively (P=0.97). Likewise, there were no significant differences in 6-MMPR levels (P=0.79). Through multivariate analysis, 6-TGN levels were found to be significantly higher in non-smokers, patients without prior surgery, and those without signs of stress-hyperarousal.
Blood concentrations of 6-TGN and 6-MMPR did not differ between patients with vs. those without 5-ASA co-treatment. Our data warrant neither more frequent lab monitoring nor dose adaptation of AZA in patients receiving concomitant 5-ASA treatment.
关于炎症性肠病(IBD)患者在接受硫唑嘌呤(AZA)或6-巯基嘌呤(6-MP)治疗时联合使用5-氨基水杨酸(5-ASA)是否会影响6-硫鸟嘌呤核苷酸(6-TGN)浓度,以及这种联合用药是否会使患者面临副作用风险,存在相互矛盾的数据。本研究的目的是确定接受AZA/6-MP治疗的患者,单独使用或与5-ASA联合使用时的6-TGN水平。
从瑞士IBD队列研究(SIBDCS)中检索接受AZA或6-MP治疗患者的可用血样。符合条件的个体分为两组:接受与未接受5-ASA联合用药的患者。测定并比较6-TGN和6-甲基巯基嘌呤核糖核苷酸(6-MMPR)水平。比较两组之间的潜在混杂因素,并将其作为多变量回归模型潜在预测因素进行评估。
在纳入本分析的110例患者中,40例在采血时同时接受5-ASA治疗。接受与未接受5-ASA联合治疗的患者,其6-TGN水平中位数分别为261和257 pmol/8×10红细胞(P = 0.97)。同样,6-MMPR水平也无显著差异(P = 0.79)。通过多变量分析发现,非吸烟者、未接受过手术的患者以及无应激性高觉醒体征者的6-TGN水平显著更高。
接受与未接受5-ASA联合治疗的患者,其6-TGN和6-MMPR的血药浓度无差异。我们的数据表明,对于接受5-ASA联合治疗的患者,既无需更频繁地进行实验室监测,也无需调整AZA剂量。