Williams C A, Bloch D A, Sibley J, Haga M, Wolfe F, Raynauld J P, Singh G, Hickey A R, Fries J F
BRI International, Inc. (C.A.W.); Department of Medicine (J.F.F., G.S.)/Division of Immunology and Rheumatology and Division of Biostatistics (D.A.B.), Stanford University; University of Saskatchewan, Saskatoon, Canada (J.S., M.H.); Arthritis Center, Wichita, Kansas (F.W.); private practice, Montreal, Canada (J.-P.R.); and Glaxo Wellcome (Research Triangle Park, NC) (A.R.H.).
J Clin Rheumatol. 1996 Apr;2(2):64-72.
Incident cases of lymphoma and leukemia in a cohort of 3824 rheumatoid arthritis (RA) patients from the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) database were identified, and the use of azathioprine, cyclophosphamide, and methotrexate was compared in a matched case-control study. Controls were matched on age, sex, year of study entry, disease duration, center, and years of follow-up. Twenty-four cases of lymphoma and 10 cases of leukemia were identified: 21% of patients with cancer versus 9% of controls had taken azathioprine [McNemar statistic 1.50 (p = 0.22), odds ratio 5.0 (95% confidence interval 0.6,236.5)]. Equal numbers of cases and controls (6% each) had taken cyclophosphamide and 18% of cases and 12% of controls had taken methotrexate [McNemar statistic 0.13 (p = 0.72), odds ratio 1.7 (0.3, 10.7)]. Results suggest but do not prove that RA patients taking azathioprine and methotrexate may have an increased risk of developing lymphoma. However, even if this increased risk can be confirmed, it accounts for only a small proportion of the greatly increased incidence of these malignancies in RA.
在来自关节炎、风湿病和衰老医学信息系统（ARAMIS）数据库的3824名类风湿性关节炎（RA）患者队列中，确定了淋巴瘤和白血病的发病病例，并在一项匹配病例对照研究中比较了硫唑嘌呤、环磷酰胺和甲氨蝶呤的使用情况。对照在年龄、性别、研究入组年份、病程、中心和随访年限方面进行匹配。确定了24例淋巴瘤和10例白血病病例：患癌患者中有21%服用过硫唑嘌呤，而对照组中这一比例为9%[麦克尼马尔统计量1.50（p = 0.22），比值比5.0（95%置信区间0.6，236.5）]。服用环磷酰胺的病例和对照数量相等（均为6%），服用甲氨蝶呤的病例为18%，对照为12%[麦克尼马尔统计量0.13（p = 0.72），比值比1.7（0.3，10.7）]。结果表明但未证实服用硫唑嘌呤和甲氨蝶呤的RA患者发生淋巴瘤的风险可能增加。然而，即使这种增加的风险能够得到证实，它在RA中这些恶性肿瘤大幅增加的发病率中也只占一小部分。
