Kwon John H, Farrell Richard J
Center for Inflammatory Bowel Disease, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Dana 501, Boston, MA 02215, USA.
Crit Rev Oncol Hematol. 2005 Oct;56(1):169-78. doi: 10.1016/j.critrevonc.2005.02.004.
Immunosuppressive agents have become an established part of the therapeutic armamentarium for inflammatory bowel disease (IBD). However, when used in transplant recipients or for other indications, agents that suppress or modulate the immune system (immunomodulators) have been associated with an increased risk of lymphoma. Fortunately, in part because of the lower doses used in IBD patients, the risk of lymphoma in IBD patients appears to be significantly less than that associated with renal and hepatic transplant-related immunosuppression. Whether the risk of azathioprine or 6-mercaptopurine associated lymphoma in IBD is real or relates to the underlying disease remains unclear. The results of several recent large well designed population-based studies suggest that the lymphoma risk associated with azathioprine and 6-mercaptopurine therapy is likely to be of minimal clinical significance compared to the established and more frequent risks of myelosuppression and infection, and is far outweighed by the clinical benefit of immunomodulator therapy in IBD. While the issue of lymphoma risk is likely to become more relevant with the growing number of biologic and immunomodulators being tested in clinical trials for IBD, early post-marketing surveillance data on infliximab suggests that the lymphoma risk may not be any greater than that associated with azathioprine and 6-mercaptopurine.
免疫抑制剂已成为炎症性肠病(IBD)治疗手段的既定组成部分。然而,当用于移植受者或其他适应症时,抑制或调节免疫系统的药物(免疫调节剂)与淋巴瘤风险增加相关。幸运的是,部分由于IBD患者使用的剂量较低,IBD患者患淋巴瘤的风险似乎明显低于与肾和肝移植相关的免疫抑制所带来的风险。IBD中硫唑嘌呤或6-巯基嘌呤相关淋巴瘤的风险是真实存在还是与潜在疾病有关仍不清楚。最近几项精心设计的大型基于人群的研究结果表明,与硫唑嘌呤和6-巯基嘌呤治疗相关的淋巴瘤风险与已确定的、更常见的骨髓抑制和感染风险相比,临床意义可能极小,并且在IBD中免疫调节剂治疗的临床益处远远超过了该风险。虽然随着越来越多的生物制剂和免疫调节剂在IBD临床试验中接受测试,淋巴瘤风险问题可能会变得更加突出,但英夫利昔单抗的早期上市后监测数据表明,其淋巴瘤风险可能并不高于硫唑嘌呤和6-巯基嘌呤。