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硫鸟嘌呤与小剂量巯嘌呤联合别嘌醇治疗炎症性肠病的对比分析。

A comparative analysis of tioguanine versus low-dose thiopurines combined with allopurinol in inflammatory bowel disease patients.

机构信息

Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.

Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands.

出版信息

Aliment Pharmacol Ther. 2020 Jun;51(11):1076-1086. doi: 10.1111/apt.15730. Epub 2020 Apr 27.

Abstract

BACKGROUND

Both tioguanine and low-dose thiopurines combined with allopurinol (LDTA) can be considered for the treatment of inflammatory bowel disease (IBD) when conventional thiopurines fail due to adverse events.

AIM

To compare the safety of tioguanine and LDTA in IBD patients.

METHODS

Inflammatory bowel disease patients who failed conventional thiopurines due to adverse events and initiated LDTA in standard care were identified in the prospective ICC Registry. IBD patients who failed conventional thiopurines due to adverse events and initiated tioguanine were enrolled in three university hospitals. Patients on concomitant biologicals were excluded. The primary outcome was discontinuation of therapy due to adverse events. Secondary outcomes included: safety outcomes and surgery-, biological- and corticosteroid-free clinical remission (physician global assessment = 0) after 104 weeks. Both multiple logistic regression and propensity score matching were used to correct for confounders.

RESULTS

In total, 182 IBD patients treated with tioguanine (n = 94) or LDTA (n = 88) were included with a median follow-up of 104 weeks (IQR 91-104). Of these, 19% (tioguanine: 20%, LDTA: 18%) of patients discontinued therapy due to adverse events. After adjusting for confounders, there were no differences in terms of discontinuation rate due to adverse events (OR 0.50, 95% CI 0.15-1.68, P = 0.26), adverse events (OR 0.89, 95% CI 0.44-1.81, P = 0.75), infections (OR 1.05, 95% CI 0.40-2.73, P = 0.93), hospitalisations (OR 2.00, 95% CI 0.64-6.23, P = 0.23) or clinical remission (OR 0.74, 95%CI 0.33-1.68, P = 0.48). All results are comparable with the propensity score matched cohort.

CONCLUSION

Nineteen percent of IBD patients with prior failure to conventional thiopurines due to adverse events discontinued therapy with tioguanine or LDTA due to adverse events. Either therapy may be considered before escalating to biological therapy.

摘要

背景

当传统的硫嘌呤因不良反应而失效时,替考拉宁和低剂量硫嘌呤联合别嘌醇(LDTA)都可以考虑用于治疗炎症性肠病(IBD)。

目的

比较替考拉宁和 LDTA 在 IBD 患者中的安全性。

方法

在前瞻性 ICC 注册中心,确定了因不良反应而导致传统硫嘌呤治疗失败并在标准治疗中开始 LDTA 的炎症性肠病患者。因不良反应而导致传统硫嘌呤治疗失败并开始使用替考拉宁的 IBD 患者在三所大学医院入组。排除同时使用生物制剂的患者。主要结局是因不良反应而停止治疗。次要结局包括:104 周后,因不良反应停止治疗、手术、停用生物制剂和皮质类固醇的临床缓解(医生整体评估=0)的安全性结局和无事件率。采用多变量逻辑回归和倾向评分匹配校正混杂因素。

结果

共纳入 182 例因不良反应而接受替考拉宁(n=94)或 LDTA(n=88)治疗的 IBD 患者,中位随访 104 周(IQR 91-104)。其中,19%(替考拉宁:20%,LDTA:18%)的患者因不良反应而停止治疗。调整混杂因素后,因不良反应停止治疗的发生率无差异(OR 0.50,95%CI 0.15-1.68,P=0.26)、不良反应(OR 0.89,95%CI 0.44-1.81,P=0.75)、感染(OR 1.05,95%CI 0.40-2.73,P=0.93)、住院(OR 2.00,95%CI 0.64-6.23,P=0.23)或临床缓解(OR 0.74,95%CI 0.33-1.68,P=0.48)。所有结果与倾向评分匹配队列的结果一致。

结论

19%的因不良反应而导致传统硫嘌呤治疗失败的 IBD 患者因不良反应停止替考拉宁或 LDTA 治疗。在升级为生物治疗之前,这两种治疗方法都可以考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6d/7318327/993b77e2ce78/APT-51-1076-g001.jpg

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