Medicine, Division of Clinical Epidemiology, McGill University Health Centre, , Montreal, Quebec, Canada.
Ann Rheum Dis. 2014 Jan;73(1):138-42. doi: 10.1136/annrheumdis-2012-202099. Epub 2013 Jan 8.
To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).
We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses.
We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls.
In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
探讨系统性红斑狼疮（SLE）中疾病活动度与治疗作为淋巴瘤危险因素的关系。
我们在一个多中心的 SLE 队列中进行了病例-队列分析。通过区域登记处的链接确定癌症。在回归模型中生成淋巴瘤的调整后 HR，用于免疫调节剂（环磷酰胺、硫唑嘌呤、甲氨蝶呤、霉酚酸酯、抗疟药、糖皮质激素）的时间依赖性暴露、人口统计学、日历年份、干燥综合征、SLE 病程和疾病活动度。我们使用调整后的平均 SLE 疾病活动指数评分（SLEDAI-2K）随时间变化，并且药物既可以分类（有/无）处理，也可以作为估计的累积剂量处理。
我们研究了 75 例淋巴瘤（72 例非霍奇金淋巴瘤，3 例霍奇金淋巴瘤）和 4961 例无癌症对照组患者。大多数淋巴瘤起源于 B 细胞。与一般人群一样，SLE 中的淋巴瘤风险在男性患者中高于女性患者，并且随年龄增长而增加。淋巴瘤发生在 SLE 诊断后平均 12.4 年（中位数 10.9 年）。未经调整和调整后的分析均未能显示疾病活动度与淋巴瘤风险之间存在明确的关联。淋巴瘤病例比无癌症对照组的患者接受环磷酰胺和更高累积类固醇的暴露量更大，但这种关联并不显著。
在这个大型 SLE 样本中，接受环磷酰胺和高累积类固醇治疗的患者淋巴瘤风险增加。疾病活动度本身与淋巴瘤风险无明显关联。进一步的研究将集中在可能与药物暴露相互作用影响 SLE 中淋巴瘤风险的遗传特征上。
