Adverse events of thiopurine immunomodulators in patients with inflammatory bowel disease

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• 作者：Cristina Ló ; pez-Martí ; n ; Marí ; a Chaparro ; Laura Espinosa ; Alicia Bejerano ; José ; Maté ; Javier P. Gisbert ; ^{gisbert@meditex.es}
• 关键词：Inflammatory bowel disease ; Azathioprine ; Mercaptopurine ; Thiopurine ; Adverse events ; Myelotoxicity ; Hepatotoxicity ; Pancreatitis
• 刊名：Gastroenterolog铆a y Hepatolog铆a
• 出版年：2011
• 期刊代码：pca167_02105705
• 类别：med
• 出版时间：June-July 2011
• 卷：34
• 期：6
• 页码：385-392
• 文件大小：152 K

摘要

Background

Thiopurine immunomodulators are the most commonly used immunosuppressants in inflammatory bowel disease.

Aims

To evaluate the incidence of adverse events (AE) in patients with inflammatory bowel disease treated with azathioprine (AZA) or 6-mercaptopurine (MP) in our hospital, the features of these effects, the distribution of socio-demographic factors, and the possible predisposing factors.

Methods

We included 377 patients with inflammatory bowel disease who were diagnosed through 2008 and who received AZA or MP during the course of their disease. We collected retrospective demographic, clinical, and laboratory data about their disease and detailed information on any AE.

Results

Fifty-one patients had some form of AE with AZA or MP (13.5%) and 11%discontinued therapy because of toxicity. Statistically significant association with Crohn's disease was found (P = .008). Myelotoxicity occurred in 18 patients (4.8%) with a mean time of laboratory abnormalities appearing after 16 months. Nine patients had hepatotoxicity secondary to these drugs (2.4%); one of them developed nodular regenerative hyperplasia and portal hypertension. Ten patients had acute pancreatitis (2.7%) with a mean time occurrence of 27 days and a statistically significant association with Crohn's disease (P = .03) and smoking (P = .01). Fifteen patients had gastrointestinal intolerance (4%) but 5 were able to continue with medication given in divided doses or switching to MP.

Conclusions

Thiopurine immunomodulators have a significant percentage of AE (13.5%), which, although usually mild, forced us to follow up all cases and sometimes even suspend treatment.