Hsu Chung-Yuan, Lin Ming-Shyan, Su Yu-Jih, Cheng Tien-Tsai, Lin Yu-Sheng, Chen Ying-Chou, Chiu Wen-Chan, Chen Tien-Hsing
Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung.
Division of Cardiology, Chang-Gung Memorial Hospital, Yunlin.
Rheumatology (Oxford). 2017 Apr 1;56(4):620-628. doi: 10.1093/rheumatology/kew457.
Immunosuppressive therapy is necessary to alter the natural course of SLE. However, immunosuppressant-related cancer risk is a major concern. The aim of this study was to determine whether immunosuppressant use is associated with cancer risk in SLE.
We designed a retrospective nested case-control study within an SLE population based on the National Health Insurance Research Database in Taiwan. We screened 14 842 patients with SLE from 2001 to 2013 and compared patients with SLE complicated by later cancer with patients with SLE but without cancer. The cumulative dose of immunosuppressants was calculated from the SLE diagnosis date to the occurrence of cancer. The immunosuppressants of interest were AZA, CYC, MTX, HCQ and systemic glucocorticoids. Adjusted odds ratios (ORs) for cancer were calculated in conditional Cox regression models after propensity score matching.
The top five types of cancers were breast (16.9%), haematological (11.7%), colorectal (11.0%), lung (10.6%) and hepatobiliary (10.4%) cancers. After matching, this study included 330 cancer patients and 1320 matched cancer-free patients. The adjusted analyses showed an association of a higher cumulative CYC dose (OR = 1.09, 95% CI: 1.04, 1.13) and lower HCQ dose (OR = 0.93, 95% CI: 0.90, 0.97) with cancer risk in comparison with the controls.
Diverse cancer risks are associated with different immunosuppressants in patients with SLE. CYC increases the risk of cancer, and HCQ decreases this risk in SLE patients, both in a dose-dependent manner.
免疫抑制治疗对于改变系统性红斑狼疮（SLE）的自然病程是必要的。然而，免疫抑制剂相关的癌症风险是一个主要问题。本研究的目的是确定SLE患者使用免疫抑制剂是否与癌症风险相关。
我们基于台湾国民健康保险研究数据库，在SLE人群中设计了一项回顾性巢式病例对照研究。我们筛选了2001年至2013年期间的14842例SLE患者，并将并发后来发生癌症的SLE患者与未患癌症的SLE患者进行比较。免疫抑制剂的累积剂量从SLE诊断日期计算至癌症发生日期。所关注的免疫抑制剂为硫唑嘌呤（AZA）、环磷酰胺（CYC）、甲氨蝶呤（MTX）、羟氯喹（HCQ）和全身性糖皮质激素。在倾向得分匹配后，通过条件Cox回归模型计算癌症的调整比值比（OR）。
前五种癌症类型为乳腺癌（16.9%）、血液系统癌症（11.7%）、结直肠癌（11.0%）、肺癌（10.6%）和肝胆癌（10.4%）。匹配后，本研究纳入了330例癌症患者和1320例匹配的无癌患者。调整分析显示，与对照组相比，CYC累积剂量较高（OR = 1.09，95%CI：1.04，1.13）和HCQ剂量较低（OR = 0.93，95%CI：0.90，0.97）与SLE患者的癌症风险相关。
SLE患者中，不同的免疫抑制剂与不同的癌症风险相关。CYC增加SLE患者癌症风险，而HCQ则降低这种风险，两者均呈剂量依赖性。
