Risk of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
Risk of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
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DOI：
10.1056/nejmoa1107829
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发表时间：
2012-05-17
影响因子：
158.5
通讯作者：
Bozic, Carmen
中科院分区：
文献类型：
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作者：
Bloomgren, Gary;Richman, Sandra;Bozic, Carmen
背景进行性多灶性白质脑病（PML）与那他珠单抗治疗相关。我们根据存在或不存在三个危险因素，量化了多发性硬化症患者发生 PML 的风险：抗 JC 病毒抗体阳性、既往使用免疫抑制剂以及那他珠单抗治疗持续时间的延长。 多发性硬化症，根据抗 JC 病毒抗体的阳性或阴性状态、之前或之前未使用免疫抑制剂以及治疗持续时间（1 至 24 个月与 25 至 48 个月）。对 5896 名多发性硬化症患者和 54 名接受那他珠单抗治疗但后来发生 PML 的多发性硬化症患者的血液样本进行了抗 JC 病毒抗体检测。 结果 截至 2012 年 2 月 29 日，在接受那他珠单抗治疗的 99,571 名患者中，有 212 例确诊 PML 病例（每 1000 名患者 2.1 例）。诊断前获得样本的所有 54 名 PML 患者的抗 JC 病毒抗体均呈阳性。当根据三个危险因素对 PML 风险进行分层时，抗 JC 病毒抗体阴性的患者发生 PML 的风险最低，发病率估计为每 1000 名患者 0.09 例或更少（95% 置信区间 [CI]，0 至 0.48）。抗 JC 病毒抗体呈阳性、开始那他珠单抗治疗前服用过免疫抑制剂、并接受那他珠单抗治疗 25 至 48 个月的患者估计风险最高（发病率，每 1000 名患者 11.1 例 [95% CI，8.3 至 14.5]）。 结论 抗 JC 病毒抗体呈阳性，既往使用过 单独或联合使用免疫抑制剂和那他珠单抗治疗持续时间的延长，与那他珠单抗治疗的多发性硬化症患者的不同程度的 PML 风险相关。
BACKGROUNDProgressive multifocal leukoencephalopathy (PML) is associated with natalizumab treatment. We quantified the risk of PML in patients with multiple sclerosis, according to the presence or absence of three risk factors: positive status with respect to anti-JC virus antibodies, prior use of immunosuppressants, and increasing duration of natalizumab treatment.METHODSWe used data from postmarketing sources, clinical studies, and an independent Swedish registry to estimate the incidence of PML among natalizumab-treated patients with multiple sclerosis, according to positive or negative status with respect to anti-JC virus antibodies, prior or no prior use of immunosuppressants, and duration of treatment (1 to 24 months vs. 25 to 48 months). Blood samples were available for anti-JC virus antibody testing from 5896 patients with multiple sclerosis and from 54 patients with multiple sclerosis who were treated with natalizumab and in whom PML later developed.RESULTSAs of February 29, 2012, there were 212 confirmed cases of PML among 99,571 patients treated with natalizumab (2.1 cases per 1000 patients). All 54 patients with PML for whom samples were available before the diagnosis were positive for anti-JC virus antibodies. When the risk of PML was stratified according to three risk factors, the risk of PML was lowest among the patients who were negative for anti-JC virus antibodies, with the incidence estimated to be 0.09 cases or less per 1000 patients (95% confidence interval [CI], 0 to 0.48). Patients who were positive for anti-JC virus antibodies, had taken immunosuppressants before the initiation of natalizumab therapy, and had received 25 to 48 months of natalizumab treatment had the highest estimated risk (incidence, 11.1 cases per 1000 patients [95% CI, 8.3 to 14.5]).CONCLUSIONSPositive status with respect to anti-JC virus antibodies, prior use of immunosuppressants, and increased duration of natalizumab treatment, alone or in combination, were associated with distinct levels of PML risk in natalizumab-treated patients with multiple sclerosis.