Department of Neurology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
Department of Radiology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
Eur J Neurol. 2016 Jun;23(6):1079-85. doi: 10.1111/ene.12988. Epub 2016 Mar 27.
John Cunningham virus (JCV) seropositivity is a risk factor for the development of natalizumab-associated progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients. When JCV seronegative patients seroconvert, their risk of developing PML increases. Limited longitudinal data exist about the seroconversion rate amongst natalizumab-treated relapsing-remitting MS (RRMS) patients. Our objective was to evaluate the seroconversion rate in a large Dutch cohort of natalizumab-treated RRMS patients. Seroconversion was defined as at least two consecutive seropositive serum samples (or cessation of therapy after a single seropositive sample because of seropositivity) after initial seronegative testing.
In our study of 179 patients for whom longitudinal blood samples were available over a long period (median 4.2 years), anti-JCV antibody indices were measured in 933 available samples. Eighty-six patients (48.0%) tested seronegative initially. Of these 86 seronegative patients, 23 patients (26.7%) seroconverted during follow-up. The annualized seroconversion rate was 7.1%. Seroconversion occurred between 9 and 90 months (median 43 months) of treatment. The rate of seroconversion was independent of follow-up duration. No significant increase was seen in the anti-JCV antibody index in the non-converting patients during the follow-up.
The annualized seroconversion rate of 7.1% in patients using natalizumab, cumulatively leading to more than 25% of seronegative patients becoming seropositive in 4 years, is of clinical relevance and should be taken into account in the risk assessment when considering the start of natalizumab therapy.
JC 病毒（JCV）血清阳性是多发性硬化症（MS）患者接受那他珠单抗治疗后发生进行性多灶性白质脑病（PML）的危险因素。当 JCV 血清阴性患者血清转阳时，其发生 PML 的风险增加。目前关于接受那他珠单抗治疗的缓解期复发型 MS（RRMS）患者血清转阳率的纵向数据有限。我们的目的是评估大量荷兰那他珠单抗治疗 RRMS 患者队列中的血清转阳率。血清转阳定义为初始血清阴性检测后至少连续两次血清阳性（或因单次血清阳性而停止治疗）。
在我们的研究中，有 179 名患者可提供长期纵向血样，对 933 份可获得的样本进行了抗 JCV 抗体指数测量。86 名患者（48.0%）初始检测血清阴性。这 86 名血清阴性患者中，23 名（26.7%）在随访期间血清转阳。年血清转阳率为 7.1%。血清转阳发生在治疗的 9 至 90 个月（中位时间为 43 个月）之间。血清转阳率与随访时间无关。在随访期间，未观察到非转阳患者的抗 JCV 抗体指数显著增加。
使用那他珠单抗的患者中，血清转阳率为 7.1%，累积导致超过 25%的血清阴性患者在 4 年内转为阳性，这具有临床相关性，在考虑开始那他珠单抗治疗时，应将其纳入风险评估中。
