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Effectiveness and safety of thioguanine as a maintenance therapy of inflammatory bowel disease: Systematic review, meta-analysis and meta-regression - 11/08/23

Doi : 10.1016/j.clinre.2023.102155 
Anuraag Jena a, Pardhu B Neelam a, Harshavardhan Telaprolu a, Uday Kiran Mangipudi a, Usha Dutta a, Shaji Sebastian b, Vishal Sharma a,
a Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India 
b IBD Unit, Hull University Teaching Hospitals NHS Trust, Hull, UK 

Corresponding author at: Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.Department of GastroenterologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia

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; I2 = 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; I2 = 24%) and 0.68 (95% C.I. 0.61 - 0.75; I2 = 18%) respectively]. The pooled remission maintenance rate was 0.71 (95% C.I. 0.58 - 0.81; I2 = 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; I2 = 75%), 0.11 (95% C.I. 0.08 - 0.16; I2 = 72%) and 0.06 (95% C.I. 0.04 - 0.09; I2 = 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.

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Keywords : Crohn's disease, Tioguanine, Thiopurine, Ulcerative colitis, Nodular regenerative hyperplasia


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Vol 47 - N° 7

Articolo 102155- Agosto 2023 Ritorno al numero
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