Efficacy and Safety of Azathio-prine in the Management of Ulcerative Colitis: A Systematic Review_West China Medical Journal

Authors：

LIU Ruming ^1,2 , WU Bing ^1,2 , ZHAO Yujin ³ ,  TANG Yao ¹

1. Department of Pharmacy, West China Hospital, 2. West China School of Pharmacy, 3. West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

TANG Yao, Email: lrm5218@yahoo.cn

Keywords：

溃疡性结肠炎; 硫唑嘌呤; 有效性; 不良反应; 系统评价

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【摘要】　目的　采用循证医学的方法评价硫唑嘌呤（aiathioprine，AZA）治疗溃疡性结肠炎（ulcerative colitis，UC）的有效性和安全性。　方法　计算机检索PubMed、Cochrane library、Embase、CNKI、维普和CBM数据库收集国内外关于AZA诊疗UC的随机对照试验（ramdomized controllel trial，RCT）。按Cochrane系统评价的方法评价纳入研究质量，并进行Meta分析。　结果　共纳入5个RCT，共262例UC患者。Meta分析结果显示，AZA治疗UC在缓解率方面与安慰剂比较，差异无统计学意义[P=1.19，95%CI（0.94，1.49），P=0.14]；在复发率方面，两者比较差异有统计学意义[P=0.72，95%CI（0.54，0.95），P=0.02]；全部不良反应方面和严重不良反应方面，两者比较差异无统计学意义，Meta分析结果分别为[P=2.52，95%CI（0.82，7.74），P=0.11]和[P=4.03，95%CI（0.88，18.53），P=0.07]。　结论　系统评价结果为AZA在疗效方面优于安慰剂，在不良反应发生率方面差异无统计学意义。但由于纳入的5个研究中没有高质量的RCT，且有1个可能产生高度偏倚，使得这一结论受到影响，有必要开展更多设计严谨，大样本、多中心的RCT。
【Abstract】　Objective　 To assess the efficacy and safety of azathio-prine in the treatment of ulcerative colitis through an evidence-based method. 　Methods　 We searched the literature from databases like PubMed, Cochrane library, CNKI, VIP, and CBM, and evaluated the quality of studies according to Cochrane systematic review. Finally, Meta-analysis was performed. 　Results　 Five randomized controlled trials (RCT) were included in this study with a total of 262 patients. Meta-analysis showed that there was no significant difference in the rate of remission between azathio-prine and placebo in treating ulcerative colitis [P=1.19, 95%CI (0.94, 1.49),P=0.14]. There was significant difference in the relapse rate between the two treating methods [P=0.72, 95%CI (0.54, 0.95),P=0.02]. In addition, there was no statistical difference in all adverse effects [P=2.52, 95%CI (0.82, 7.74),P=0.11] and serious adverse effects [P=4.03, 95%CI (0.88, 18.53),P=0.07] between the two treating methods. 　Conclusion　 In the treatment of ulcerative colitis, azathio-prine has a significant advantage in efficacy than placebo, but there is no significant difference in the rate of adverse events between the two groups. However, none of the 5 RCT included in this review has a high quality and one of them even probably has a high bias, which has a big influence on our conclusion. Consequently, multi-center large-scale randomized controlled trials of higher quality are needed to make confirmation.

Citation： LIU Ruming,WU Bing,ZHAO Yujin,TANG Yao. Efficacy and Safety of Azathio-prine in the Management of Ulcerative Colitis: A Systematic Review. West China Medical Journal, 2011, 26(5): 730-734. doi: Copy

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13.	Rosenberg JL, Wall AJ, Levin B, et al. A controlled trial of azathioprine in the management of chronic ulcerative colitis[J]. Gastroenterology, 1975, 69(1): 96-99.
14.	Hawthorne AB, Logan RF, Hawkey C, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis[J]. BMJ, 1992, 305(6844): 20-22.
15.	Sood A, Midha V, Sood N, et al. Role of azathioprine in severe ulcerative colitis: one-year, placebo-controlled, randomized trial[J]. Indian J Gastroenterol, 2000, 19(1): 14-16.
16.	Sood A, Kaushal V, Midha V, et al. The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis[J]. J Gastroenterol, 2002, 37(4): 270-274.

1. 　Ng SC, Kamm MA. Therapeutic strategies for the management of ulcerative colitis[J]. Inflamm Bowel Dis, 2009, 15(6): 935-950.
2. 　田士军. 溃疡性结肠炎的药物治疗进展[J]. 医学综述, 2009, 15(17): 2612-2615.
3. 　Bowen GE, Irons GV Jr, Rhodes Jb, et al. Early experiences with azathioprine in ulcerative colitis; a note of caution[J]. JAMA, 1966, 195(6): 460-464.
4. 　Kornbluth A, Sachar DB. Ulcerative colitis[J]. Am J Gastroenterol, 1997, 92(2): 204-211.
5. 　Su C, Lichtenstein GR. Treatment of inflammatory bowel disease with azathiprine and 6-mercaptopurine[J]. Gastroenterol Clin N Am, 2004, 33(2): 209-234.
6. 　Kim DU, Kim YH, Kim BJ, et al. The efficacy of low dose azathioprine/6-mercaptopurine in patients with inflammatory bowel disease[J]. Hepatogastroenterology, 2009, 56(94-95): 1395-1402.
7. 　Lichtenstein GR, Abreu MT, Cohen R, et al. American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease[J]. Gastroenterology, 2006, 130(3): 940-987.
8. 　Connell WR, Kamm MA, Ritchie JK, et al. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience[J]. Gut, 1993, 34(8): 1081-1085.
9. 　Greenstein AJ, Mullin GE, Strauchen JA, et al. Lymphoma in inflammatory bowel disease[J]. Cancer, 1992, 69(5): 1119-1123.
10. 　Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version. 5. 0. 1 [EB/OL]. [updated February 2008]. [2009-2-10]. www.cochrane-handbook.com.
11. 　Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis[J]. Stat Med, 2002, 21(11): 1539-1558.
12. 　Jewell DP, Truelove SC. Azathioprine in ulcerative colitis: final report on controlled therapeutic trial[J]. Br Med J, 1974, 4(5945): 627-630.
13. 　Rosenberg JL, Wall AJ, Levin B, et al. A controlled trial of azathioprine in the management of chronic ulcerative colitis[J]. Gastroenterology, 1975, 69(1): 96-99.
14. 　Hawthorne AB, Logan RF, Hawkey C, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis[J]. BMJ, 1992, 305(6844): 20-22.
15. 　Sood A, Midha V, Sood N, et al. Role of azathioprine in severe ulcerative colitis: one-year, placebo-controlled, randomized trial[J]. Indian J Gastroenterol, 2000, 19(1): 14-16.
16. 　Sood A, Kaushal V, Midha V, et al. The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis[J]. J Gastroenterol, 2002, 37(4): 270-274.

West China Medical Journal

Efficacy and Safety of Azathio-prine in the Management of Ulcerative Colitis: A Systematic Review

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