Introduction

Natalizumab (NTZ) can be associated with an opportunistic infection, progressive multifocal leukoencephalopathy (PML), caused by John Cunningham virus (JCV). High titer of anti-JCV antibody (JCV index) in patients treated with NTZ for over 2 years limit it use, leading to treatment discontinuation.

Objective

Aim of the study was to investigate the JCV index changes pre, during and post NTZ treatment and describe the trend after a long period of NTZ discontinuation.

Methods

Patients with relapsing–remitting multiple sclerosis (RR–MS) treated with NTZ between 2010 and 2018 were enrolled in this retrospective-prospective observational study. Inclusion criteria were: (1) diagnosis of RR–MS according to the McDonald criteria 2010, (2) at least six NTZ administrations, (3) at least two determinations of JCV Index during the follow-up period, (4) NTZ discontinuation period for more than 6 months. JCV index was determined by STRATIFY II. There were three different timepoints: NTZ initiation (T0), NTZ discontinuation (T1) and time after NTZ suspension (T2). Seroconversion was defined as changing status of serum JCV antibody. Main outcomes were the JCV index changes and the rate of seroconversion.

Results

At baseline we enrolled 285 patients (208 JCV negative, 67 JCV positive, and 10 not available). There was a statistically significant increase of JCV index during NTZ treatment period (T0 vs T1, p =0.0009) and during NTZ discontinuation period (T1 vs T2, p =0.04). Patients seroconverted to a positive status more frequently during NTZ treatment than after discontinuation (p =0.008). Moreover, patients who shifted to fingolimod (FTY) as exit strategy after NTZ discontinuation, showed a statistically significant increase of JCV index.

Conclusion

Our data confirmed that a high percentage of patients shift to or remain in a positive JCV status during NTZ treatment and after discontinuation. NTZ suspension seems not to be able to interfere on JCV status modification over an extended period. The choice of alternative treatment as exit strategy after NTZ discontinuation should be carefully considered because it could negatively influence the PML risk stratification of patients.

中文翻译：

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用那他珠单抗治疗的大量多发性硬化症患者中抗 JCV 抗体状态的变化。

介绍

那他珠单抗 (NTZ) 可能与由约翰·坎宁安病毒 (JCV) 引起的机会性感染、进行性多灶性白质脑病 (PML) 相关。接受 NTZ 治疗超过 2 年的患者的高滴度抗 JCV 抗体（JCV 指数）限制了它的使用，导致治疗中断。

客观的

该研究的目的是调查 NTZ 治疗前、治疗中和治疗后 JCV 指数的变化，并描述长期停用 NTZ 后的趋势。

方法

2010 年至 2018 年间接受 NTZ 治疗的复发缓解型多发性硬化症 (RR-MS) 患者参加了这项回顾性-前瞻性观察研究。纳入标准为：(1) 根据 McDonald 标准 2010 诊断为 RR-MS，(2) 至少六次 NTZ 给药，(3) 在随访期间至少测定两次 JCV 指数，(4) 停用 NTZ期限超过 6 个月。JCV 指数由 STRATIFY II 确定。存在三个不同的时间点：NTZ 开始 (T0)、NTZ 终止 (T1) 和 NTZ 暂停后的时间 (T2)。血清转化定义为血清 JCV 抗体状态的变化。主要结果是 JCV 指数变化和血清转化率。

结果

在基线时，我们招募了 285 名患者（208 名 JCV 阴性，67 名 JCV 阳性，10 名不可用）。在 NTZ 治疗期间（T0 对 T1，p  = 0.0009）和在 NTZ 停药期间（T1 对 T2，p  = 0.04），JCV 指数在统计学上显着增加。在 NTZ 治疗期间，患者血清转化为阳性状态的频率高于停药后 ( p  = 0.008)。此外，在 NTZ 停药后转用芬戈莫德 (FTY) 作为退出策略的患者显示 JCV 指数在统计学上显着增加。

结论

我们的数据证实，在 NTZ 治疗期间和停药后，很大比例的患者转变为或保持 JCV 阳性状态。NTZ 暂停似乎无法在很长一段时间内干扰 JCV 状态修改。应仔细考虑选择替代治疗作为停用 NTZ 后的退出策略，因为它可能会对患者的 PML 风险分层产生负面影响。