Autoimmune Antibodies and Recurrence-Free Interval in Melanoma Patients Treated With Adjuvant Interferon
Autoimmune Antibodies and Recurrence-Free Interval in Melanoma Patients Treated With Adjuvant Interferon
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DOI：
10.1093/jnci/djp132
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发表时间：
2009-06-16
影响因子：
10.3
通讯作者：
Eggermont, Alexander M. M.
中科院分区：
文献类型：
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作者：
Bouwhuis, Marna G.;Suciu, Stefan;Eggermont, Alexander M. M.
据报道，在接受辅助干扰素（IFN）-α 2b治疗的黑色素瘤患者中，自身抗体的出现和自身免疫的临床表现与预后改善相关。我们在两项随机试验中评估了治疗开始后自身抗体的出现与无复发间隔的相关性，这些试验比较了中等剂量IFN治疗黑色素瘤患者的观察结果。和抗核抗体测定使用酶-在欧洲癌症研究和治疗组织（EORTC）18952和北欧IFN试验中，分别在187和356名患者中进行了连接免疫吸附测定，随机分配前即刻和随机分配后长达3年。在基线时三种自身抗体均阴性的患者中，通过三种考克斯模型评估三种自身抗体中至少一种抗体的存在与复发风险的相关性（125例来自EORTC 18952试验，230例来自Nordic IFN试验）：1）将自身抗体的出现视为时间无关变量的模型，2）一旦获得自身抗体的阳性测试就认为患者自身抗体阳性的模型，和3）其中患者的状态由最近的自身抗体测试定义的模型。所有的统计学检验都是双侧的，当作为时间独立变量（模型1）处理时，在两项试验中，自身抗体的出现与无复发间期的改善相关（EORTC 18952，风险比[HR] = 0.41，95%置信区间[CI] = 0.25至0.68，P <0.001;和Nordic IFN，HR = 0.51，95% CI = 0.34至0.76，P < .001）。然而，在对时间偏差进行校正后，这种关联较弱，没有统计学意义。（模型2：EORTC 18952，HR = 0.81，95%CI = 0.46至1.40，P = 0.44; Nordic IFN，HR = 0.85，95%CI = 0.55至1.30，P = 0.45;模型3：EORTC 18952，HR = 1.05，95% CI = 0.59 - 1.87，P = 0.88;和Nordic IFN，HR = 0.78，95%CI = 0.49至1.24，P = 0.30）。在IFN治疗黑色素瘤患者的两项随机试验中，当校正复发时间偏倚时，自身抗体的出现与无复发间期的改善没有强相关性。
Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha 2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation of treatment with recurrence-free interval in two randomized trials that compared intermediate doses of IFN with observation for the treatment of melanoma patients.Serum levels of anticardiolipin, antithyroglobulin, and antinuclear antibodies were determined using enzyme-linked immunosorbent assays in 187 and 356 patients in the European Organization for Research and Treatment of Cancer (EORTC) 18952 and Nordic IFN trials, respectively, immediately before and up to 3 years after random assignment. The association of the presence of at least one of the three autoantibodies with risk of recurrence was assessed by three Cox models in patients negative for all three autoantibodies at baseline (125 from the EORTC 18952 trial and 230 from the Nordic IFN trial): 1) a model that considered appearance of autoantibodies as a time-independent variable, 2) one that considered a patient autoantibody positive once a positive test for an autoantibody was obtained, and 3) a model in which the status of the patient was defined by the most recent autoantibody test. All statistical tests were two-sided.When treated as a time-independent variable (model 1), appearance of autoantibodies was associated with improved relapse-free interval in both trials (EORTC 18952, hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.25 to 0.68, P < .001; and Nordic IFN, HR = 0.51, 95% CI = 0.34 to 0.76, P < .001). However, on correction for guarantee-time bias, the association was weaker and not statistically significant (model 2: EORTC 18952, HR = 0.81, 95% CI = 0.46 to 1.40, P = .44; and Nordic IFN, HR = 0.85, 95% CI = 0.55 to 1.30, P = .45; model 3: EORTC 18952, HR = 1.05, 95% CI = 0.59 to 1.87, P = .88; and Nordic IFN, HR = 0.78, 95% CI = 0.49 to 1.24, P = .30).In two randomized trials of IFN for the treatment of melanoma patients, appearance of autoantibodies was not strongly associated with improved relapse-free interval when correction was made for guarantee-time bias.