柳汝明 1,2 , 吳斌 1,2 , 趙雨晉 3 , 唐堯 1
  • 四川大學(xué)（成都，610041） 1 華西醫(yī)院藥劑科，2 華西藥學(xué)院，3 華西臨床醫(yī)學(xué)院;

【摘要】　目的　 采用循證醫(yī)學(xué)的方法評(píng)價(jià)硫唑嘌呤（aiathioprine，AZA）治療潰瘍性結(jié)腸炎（ulcerative colitis，UC）的有效性和安全性。　方法　 計(jì)算機(jī)檢索PubMed、Cochrane library、Embase、CNKI、維普和CBM數(shù)據(jù)庫(kù)收集國(guó)內(nèi)外關(guān)于AZA診療UC的隨機(jī)對(duì)照試驗(yàn)（ramdomized controllel trial，RCT）。按Cochrane系統(tǒng)評(píng)價(jià)的方法評(píng)價(jià)納入研究質(zhì)量，并進(jìn)行Meta分析。　結(jié)果　 共納入5個(gè)RCT，共262例UC患者。Meta分析結(jié)果顯示，AZA治療UC在緩解率方面與安慰劑比較，差異無(wú)統(tǒng)計(jì)學(xué)意義[P=1.19，95%CI（0.94，1.49），P=0.14]；在復(fù)發(fā)率方面，兩者比較差異有統(tǒng)計(jì)學(xué)意義[P=0.72，95%CI（0.54，0.95），P=0.02]；全部不良反應(yīng)方面和嚴(yán)重不良反應(yīng)方面，兩者比較差異無(wú)統(tǒng)計(jì)學(xué)意義，Meta分析結(jié)果分別為[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]。　結(jié)論　 系統(tǒng)評(píng)價(jià)結(jié)果為AZA在療效方面優(yōu)于安慰劑，在不良反應(yīng)發(fā)生率方面差異無(wú)統(tǒng)計(jì)學(xué)意義。但由于納入的5個(gè)研究中沒(méi)有高質(zhì)量的RCT，且有1個(gè)可能產(chǎn)生高度偏倚，使得這一結(jié)論受到影響，有必要開(kāi)展更多設(shè)計(jì)嚴(yán)謹(jǐn)，大樣本、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.

引用本文： 柳汝明,吳斌,趙雨晉,唐堯. 硫唑嘌呤治療潰瘍性結(jié)腸炎有效性及安全性的系統(tǒng)評(píng)價(jià). 華西醫(yī)學(xué), 2011, 26(5): 730-734. doi: 復(fù)制

1. 　Ng SC, Kamm MA. Therapeutic strategies for the management of ulcerative colitis[J]. Inflamm Bowel Dis, 2009, 15(6): 935-950.
2. 　田士軍. 潰瘍性結(jié)腸炎的藥物治療進(jìn)展[J]. 醫(yī)學(xué)綜述, 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.
  1. 1. 　Ng SC, Kamm MA. Therapeutic strategies for the management of ulcerative colitis[J]. Inflamm Bowel Dis, 2009, 15(6): 935-950.
  2. 2. 　田士軍. 潰瘍性結(jié)腸炎的藥物治療進(jìn)展[J]. 醫(yī)學(xué)綜述, 2009, 15(17): 2612-2615.
  3. 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. 4. 　Kornbluth A, Sachar DB. Ulcerative colitis[J]. Am J Gastroenterol, 1997, 92(2): 204-211.
  5. 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. 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. 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. 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. 9. 　Greenstein AJ, Mullin GE, Strauchen JA, et al. Lymphoma in inflammatory bowel disease[J]. Cancer, 1992, 69(5): 1119-1123.
  10. 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. 11. 　Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis[J]. Stat Med, 2002, 21(11): 1539-1558.
  12. 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. 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. 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. 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. 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.