Plavina Tatiana, Subramanyam Meena, Bloomgren Gary, Richman Sandra, Pace Amy, Lee Sophia, Schlain Brian, Campagnolo Denise, Belachew Shibeshih, Ticho Barry
Biogen Idec, Cambridge, MA.
Ann Neurol. 2014 Dec;76(6):802-12. doi: 10.1002/ana.24286. Epub 2014 Oct 24.
The increased risk of progressive multifocal leukoencephalopathy (PML) with natalizumab treatment is associated with the presence of anti-JC virus (JCV) antibodies. We analyzed whether anti-JCV antibody levels, measured as index, may further define PML risk in seropositive patients.
The association between serum or plasma anti-JCV antibody levels and PML risk was examined in anti-JCV antibody-positive multiple sclerosis (MS) patients from natalizumab clinical studies and postmarketing sources. For PML and non-PML patients, the probabilities of having an index below and above a range of anti-JCV antibody index thresholds were calculated using all available data and applied to the PML risk stratification algorithm. Longitudinal stability of anti-JCV antibody index was also evaluated.
Anti-JCV antibody index data were available for serum/plasma samples collected >6 months prior to PML diagnosis from 71 natalizumab-treated PML patients and 2,522 non-PML anti-JCV antibody-positive patients. In patients with no prior immunosuppressant use, anti-JCV antibody index distribution was significantly higher in PML patients than in non-PML patients (p < 0.0001). Among patients who were anti-JCV antibody negative at baseline in the AFFIRM and STRATIFY-1 trials, 97% remained consistently negative or below an index threshold of 1.5 over 18 months. Retrospective analyses of pre-PML samples collected longitudinally from PML patients displayed sustained higher anti-JCV antibody index over time.
Anti-JCV antibody levels in serum/plasma, measured as index, may differentiate PML risk in anti-JCV antibody-positive MS patients with no prior immunosuppressant use. Continued evaluation of anti-JCV antibody index and PML risk is warranted.
那他珠单抗治疗导致进行性多灶性白质脑病（PML）风险增加与抗JC病毒（JCV）抗体的存在有关。我们分析了以指数衡量的抗JCV抗体水平是否可进一步界定血清反应阳性患者的PML风险。
在来自那他珠单抗临床研究及上市后资料的抗JCV抗体阳性的多发性硬化症（MS）患者中，检测血清或血浆抗JCV抗体水平与PML风险之间的关联。对于PML患者和非PML患者，使用所有可用数据计算抗JCV抗体指数低于和高于一系列阈值时的概率，并将其应用于PML风险分层算法。还评估了抗JCV抗体指数的纵向稳定性。
从71例接受那他珠单抗治疗的PML患者和2522例抗JCV抗体阳性的非PML患者中获取了在PML诊断前6个月以上采集的血清/血浆样本的抗JCV抗体指数数据。在未使用过免疫抑制剂的患者中，PML患者的抗JCV抗体指数分布显著高于非PML患者（p < 0.0001）。在AFFIRM和STRATIFY - 1试验中基线抗JCV抗体阴性的患者中，97%在18个月内始终保持阴性或低于指数阈值1.5。对PML患者纵向采集的PML前样本进行回顾性分析显示，抗JCV抗体指数随时间持续升高。
以指数衡量的血清/血浆中的抗JCV抗体水平可区分未使用过免疫抑制剂的抗JCV抗体阳性MS患者的PML风险。有必要继续评估抗JCV抗体指数和PML风险。
