Kandiel A, Fraser A G, Korelitz B I, Brensinger C, Lewis J D
Department of Gastroenterology and Hepatology, The Cleveland Clinic, Ohio, USA.
Gut. 2005 Aug;54(8):1121-5. doi: 10.1136/gut.2004.049460.
Inflammatory bowel disease (IBD) is commonly treated with immunomodulators such as azathioprine and 6-mercaptopurine (6-MP). Studies examining lymphoma risk in IBD patients treated with these medications have been underpowered and have yielded conflicting conclusions.
The purpose of this meta-analysis was to provide a more precise estimate of the relative risk of lymphoma among IBD patients treated with azathioprine or 6-MP.
Studies were included if they were English language, full article, cohort studies specifically designed to evaluate cancer as an adverse outcome of treatment with azathioprine or 6-MP. Pooled standardised incidence ratios were calculated to estimate the relative risk of lymphoma associated with therapy. Heterogeneity was assessed using Poisson regression. Sensitivity analyses examined the influence of individual studies on risk estimate and heterogeneity statistics.
Six studies were identified that met our inclusion criteria. When the data were combined across all studies, the pooled relative risk was 4.18 (95% confidence interval 2.07-7.51; 11 observed cases, 2.63 expected). Sensitivity analysis showed that exclusion of any one study had a relatively small effect on the pooled relative risk estimate (range 3.49-5.21) but excluding either the study with the highest or lowest estimated relative risk eliminated the statistically significant heterogeneity.
Our data suggest an approximate fourfold increased risk of lymphoma in IBD patients treated with azathioprine/6-MP. The increased risk of lymphoma could be a result of the medications, the severity of the underlying disease, or a combination of the two.
炎症性肠病（IBD）通常采用免疫调节剂进行治疗，如硫唑嘌呤和6-巯基嘌呤（6-MP）。对接受这些药物治疗的IBD患者淋巴瘤风险的研究样本量不足，且得出了相互矛盾的结论。
本荟萃分析的目的是更精确地估计接受硫唑嘌呤或6-MP治疗的IBD患者患淋巴瘤的相对风险。
纳入的研究需为英文全文队列研究，专门设计用于评估硫唑嘌呤或6-MP治疗的不良后果癌症。计算合并标准化发病率比以估计与治疗相关的淋巴瘤相对风险。使用泊松回归评估异质性。敏感性分析检验了个别研究对风险估计和异质性统计的影响。
确定了6项符合我们纳入标准的研究。当合并所有研究的数据时，合并相对风险为4.18（95%置信区间2.07 - 7.51；观察到11例病例，预期2.63例）。敏感性分析表明，排除任何一项研究对合并相对风险估计的影响相对较小（范围3.49 - 5.21），但排除估计相对风险最高或最低的研究可消除统计学上的显著异质性。
我们的数据表明，接受硫唑嘌呤/6-MP治疗的IBD患者患淋巴瘤的风险增加了约四倍。淋巴瘤风险增加可能是药物、潜在疾病的严重程度或两者共同作用的结果。
