Masunaga Yukari, Ohno Keiko, Ogawa Ryuichi, Hashiguchi Masayuki, Echizen Hirotoshi, Ogata Hiroyasu
Student, Graduate School of Pharmaceutical Sciences, Department of Pharmacy, Hatsudai Rehabilitation Hospital, Tokyo.
Ann Pharmacother. 2007 Jan;41(1):21-8. doi: 10.1345/aph.1H219. Epub 2007 Jan 2.
There is a concern as to whether long-term administration of immunosuppressants in patients with inflammatory bowel disease (IBD) would increase the risk of malignancy.
To compare the risks of developing malignancy between patients with IBD treated with immunosuppressive agents and patients with IBD not receiving these agents.
A systematic literature review was conducted, and a meta-analysis was performed on data retrieved from cohort studies that followed patients with IBD who received immunosuppressive agents for more than a year and documented the incidence of newly developed malignancy. An electronic search was conducted using MEDLINE (1966-September 2006), the Cochrane Library (issue 3, 2006), and Japana Centra Revuo Medicina (1981-September 2006). Medical subject headings used in the searches were azathioprine, 6-mercaptopurine, cyclosporine, methotrexate, tacrolimus, inflammatory bowel disease, and neoplasms. We imposed no language limitation in the searches. Additionally, a manual search of reference listings from all articles retrieved from the electronic databases was performed. Using data obtained from control groups or population-based studies, the incidence of newly developed malignancy in patients with IBD treated with immunosuppressive agents was compared with that of patients with IBD who were not receiving immunosuppressive agents. Statistical analysis for the change in risk of developing malignancy was performed using the weighted mean difference (WMD) normalized to per person-year and its 95% confidence interval.
Nine cohort studies met the inclusion criteria for this meta-analysis. Analysis of these studies showed no discernible difference (WMD -0.3 x 10(-3)/person-year; 95% CI -1.2 x 10(-3) to 0.7 x 10(-3)) in the incidence of any kind of malignancy in patients with IBD who received immunosuppressants compared with those who did not receive immunosuppressants. No significant difference in WMD was observed when the data from patients with either Crohn's disease (CD) or ulcerative colitis (UC) were analyzed separately.
Our findings suggest that the administration of immunosuppressive agents in patients with either CD or UC probably does not confer a significantly increased risk of malignancy compared with patients with IBD who are not receiving these agents.
炎症性肠病（IBD）患者长期使用免疫抑制剂是否会增加患恶性肿瘤的风险备受关注。
比较接受免疫抑制剂治疗的IBD患者与未接受这些药物治疗的IBD患者发生恶性肿瘤的风险。
进行了一项系统的文献综述，并对从队列研究中检索到的数据进行荟萃分析，这些队列研究追踪了接受免疫抑制剂治疗超过一年的IBD患者，并记录了新发生恶性肿瘤的发生率。使用MEDLINE（1966年至2006年9月）、Cochrane图书馆（2006年第3期）和日本医学中央杂志（1981年至2006年9月）进行电子检索。检索中使用的医学主题词为硫唑嘌呤、6-巯基嘌呤、环孢素、甲氨蝶呤、他克莫司、炎症性肠病和肿瘤。检索过程中不设语言限制。此外，还对从电子数据库中检索到的所有文章的参考文献列表进行了手工检索。利用从对照组或基于人群的研究中获得的数据，比较接受免疫抑制剂治疗的IBD患者与未接受免疫抑制剂治疗的IBD患者新发生恶性肿瘤的发生率。使用归一化为人年的加权平均差（WMD）及其95%置信区间对发生恶性肿瘤风险的变化进行统计分析。
九项队列研究符合本荟萃分析的纳入标准。对这些研究的分析表明，接受免疫抑制剂治疗的IBD患者与未接受免疫抑制剂治疗的患者相比，任何类型恶性肿瘤的发生率没有明显差异（WMD -0.3×10⁻³/人年；95%CI -1.2×10⁻³至0.7×10⁻³）。分别分析克罗恩病（CD）或溃疡性结肠炎（UC）患者的数据时，未观察到WMD有显著差异。
我们的研究结果表明，与未接受这些药物治疗的IBD患者相比，CD或UC患者使用免疫抑制剂可能不会显著增加患恶性肿瘤的风险。
