Exposure to Immunosuppressive Drugs & Cancer Risk in SLE

描述(由申请人提供)： 在过去的20年里，人们对自身免疫和癌症之间的联系的兴趣已经升级。系统性红斑狼疮(SLE)是自身免疫性疾病的原型，是发生在育龄妇女中的第二大常见自身免疫性疾病。以前的研究在评估SLE和癌症之间的潜在关系时没有定论；然而，我们的调查团队对7200多名SLE患者进行了59,000年以上的随访研究，结果证实所有癌症(标准化发病率比，[SIR]1.2，95%可信区间，[CI]1.1，1.4)和某些癌症，特别是血液病(SIR 3.0，95%CI 2.3，3.8)，在SLE中发生的频率比预期更高。此外，我们的队列研究显示，最高点估计或SIRS发生在SLE的第一年，这表明癌症风险不能完全用免疫抑制药物(ISD)的累积剂量来解释。因此，需要阐明ISDS在SLE癌症风险中的作用，合乎逻辑的下一步是检验假设，探索暴露于ISDS和不暴露于ISDS的SLE对癌症的易感性。我们建议在我们独特的国际多中心队列研究的背景下，进行一项病例队列研究(经典嵌套病例对照设计的灵活而有效的变体)，以确定ISDS(硫唑嘌呤、环磷酰胺、甲氨蝶呤或环孢菌素)是否影响SLE的癌症风险，特别是针对血液系统恶性肿瘤。在初步分析中，在控制其他药物使用、年龄、性别和SLE病程和损害的模型中，将使用修正的COX比例风险回归来计算暴露于ISDS后发生血液病的风险比。在二次分析中，我们将检查其他临床因素的潜在作用，如继发性干燥综合征或影响因素，如吸烟。如果某些ISDS与癌症风险有关，处方模式可能会改变。这项研究还可能提供关于癌症和自身免疫之间潜在联系的新信息。

DESCRIPTION (provided by applicant): In the past 2 decades, interest in links between autoimmunity and cancer have escalated. Systemic lupus erythematosus (SLE), the prototype autoimmune disease, is the 2nd most common autoimmune disorder occurring in childbearing women. Previous studies were inconclusive when evaluating the potential relationship between SLE and cancer; however, our investigative team conducted a cohort study of 7200+ SLE patients with 59,000+ follow-up years, where results confirm that all cancers (Standardized Incidence Ratio, [SIR] 1.2, 95% Confidence Interval, [CI] 1.1, 1.4) and certain cancers, particularly hematologic (SIR 3.0, 95% CI 2.3, 3.8), occur more frequently than expected in SLE. Further, our cohort study shows the highest point estimates or SIRs occur in the 1st year of SLE, suggesting that cancer risk is not completely explained by the cumulative dose of immunosuppressive drug (ISD) exposure. Therefore, elucidation of the role of ISDs with respect to cancer risk in SLE is needed and the logical next step is to test hypotheses exploring susceptibility to cancer in SLE with and without exposures to ISDs. We are proposing to conduct a case-cohort study (a flexible and efficient varation of the classical nested case-control design), within the context of our unique international multi-center cohort study, to determine whether ISDs (azathiopdne, cyclophosphamide, methotrexate, or cyclosporin) influence cancer risk, specifically targeting hematologic malignancies, in SLE. In the primary analysis, modified Cox proportional hazards regression will be used to calculate the risk ratio for hematologic cancer development after exposure to ISDs in a model that controls for other medication use, age, sex, and SLE disease duration and damage. In secondary analyses, we will examine the potential role of other clinical factors, such as secondary Sjogren's syndrome or effect modifiers, such as smoking. If certain ISDs are linked to cancer risk, prescribing patterns may change. This study may also provide new information about potential links between cancer and autoimmunity.