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硫鸟嘌呤作为炎症性肠病维持治疗的有效性和安全性:系统评价、荟萃分析和荟萃回归。

Effectiveness and safety of thioguanine as a maintenance therapy of inflammatory bowel disease: Systematic review, meta-analysis and meta-regression.

机构信息

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

IBD Unit, Hull University Teaching Hospitals NHS Trust, Hull, UK.

出版信息

Clin Res Hepatol Gastroenterol. 2023 Aug;47(7):102155. doi: 10.1016/j.clinre.2023.102155. Epub 2023 Jun 8.

Abstract

INTRODUCTION

Thiopurines are an important therapy for the maintenance of remission in inflammatory bowel disease (IBD). However, the use of thioguanine has been limited by concerns regarding its toxicity. We performed a systematic review to evaluate its effectiveness and safety in IBD.

METHODS

Electronic databases were searched to identify studies reporting clinical responses and/or adverse events of thioguanine therapy in IBD. We calculated the pooled clinical response and clinical remission rates of thioguanine in IBD. Subgroup analyses were done for the dosage of thioguanine and the type of studies (prospective or retrospective). Meta-Regression was used to analyze the impact of dose on clinical efficacy and occurrence of nodular regenerative hyperplasia.

RESULTS

A total of 32 studies were included. The pooled clinical response rate of thioguanine therapy in IBD was 0.66 (95% C.I. 0.62 - 0.70; I = 16%). The pooled clinical response rate with low-dose was similar to high-dose thioguanine therapy [0.65 (95% C.I. 0.59 - 0.70; I = 24%) and 0.68 (95% C.I. 0.61 - 0.75; I = 18%) respectively]. The pooled remission maintenance rate was 0.71 (95% C.I. 0.58 - 0.81; I = 86%). The pooled rates of occurrence of nodular regenerative hyperplasia, liver function tests abnormalities and cytopenia were 0.04 (95% C.I. 0.02 - 0.08; I = 75%), 0.11 (95% C.I. 0.08 - 0.16; I = 72%) and 0.06 (95% C.I. 0.04 - 0.09; I = 62%) respectively. Meta-regression suggested that the risk of nodular regenerative hyperplasia is related to the dose of thioguanine.

CONCLUSION

TG is an efficacious and well-tolerated drug in most patients with IBD. Nodular regenerative hyperplasia, cytopenias, and liver function abnormalities occur in a small subset. Future studies should look into TG as primary therapy in IBD.

摘要

简介

硫嘌呤类药物是炎症性肠病(IBD)维持缓解的重要治疗方法。然而,由于担心其毒性,硫鸟嘌呤的使用受到限制。我们进行了一项系统评价,以评估其在 IBD 中的疗效和安全性。

方法

电子数据库检索报告硫嘌呤治疗 IBD 的临床反应和/或不良事件的研究。我们计算了硫嘌呤治疗 IBD 的临床反应和临床缓解率的汇总数据。根据硫嘌呤的剂量和研究类型(前瞻性或回顾性)进行亚组分析。Meta 回归用于分析剂量对临床疗效和结节性再生性增生发生的影响。

结果

共纳入 32 项研究。硫嘌呤治疗 IBD 的汇总临床反应率为 0.66(95%置信区间 0.62-0.70;I=16%)。低剂量与高剂量硫嘌呤治疗的临床反应率相似[0.65(95%置信区间 0.59-0.70;I=24%)和 0.68(95%置信区间 0.61-0.75;I=18%)]。维持缓解的汇总率为 0.71(95%置信区间 0.58-0.81;I=86%)。结节性再生性增生、肝功能检查异常和细胞减少症的汇总发生率分别为 0.04(95%置信区间 0.02-0.08;I=75%)、0.11(95%置信区间 0.08-0.16;I=72%)和 0.06(95%置信区间 0.04-0.09;I=62%)。Meta 回归表明,结节性再生性增生的风险与硫嘌呤的剂量有关。

结论

TG 是大多数 IBD 患者有效且耐受良好的药物。结节性再生性增生、细胞减少症和肝功能异常在一小部分患者中发生。未来的研究应将 TG 作为 IBD 的主要治疗方法进行研究。

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