Department of Neurology, VU University Medical Center, The Netherlands.
Mult Scler. 2013 Apr;19(5):593-600. doi: 10.1177/1352458512460604. Epub 2012 Sep 19.
Antibodies against natalizumab have been found in 4.5-14.1% of natalizumab-treated multiple sclerosis (MS) patients. If antibodies persist, they are associated with an adverse effect on treatment response. However, it has proved to be difficult to standardize anti-drug antibody measurements.
The purpose of this study was to evaluate the clinical and radiological impact of serum natalizumab concentrations and their relation with anti-natalizumab antibodies in MS patients.
In this prospective observational cohort study of 73 consecutive patients treated with natalizumab, we measured serum natalizumab levels and antibody titers before the start of natalizumab treatment, at weeks 12 and 24 and annually after natalizumab initiation. Antibodies against natalizumab were measured by radioimmunoassay and serum natalizumab concentrations using a newly developed enzyme linked immunosorbent assay (ELISA). Magnetic resonance imaging (MRI) scan and clinical evaluation were performed before the start of natalizumab treatment and subsequently every year.
Antibodies were detected in 58% of the natalizumab-treated patients. All patients developed their antibodies before week 24. The large majority of these patients reverted to neutralizing antibody (NAb) negative status during follow-up. The presence of antibodies was inversely correlated with serum natalizumab concentration (p<0.001). Only high antibody titers are associated with very low or undetectable serum natalizumab concentration. Both high antibody titers and low serum natalizumab concentrations are associated with relapses and gadolinium-enhancing lesions on MRI.
Our data show that both low natalizumab serum concentration and high antibody titers are associated with a lack of efficacy of natalizumab. Measuring serum natalizumab, using a highly specific assay, might lead to more enhanced precision using natalizumab in individual patients.
在接受那他珠单抗治疗的多发性硬化症（MS）患者中，有 4.5%-14.1%检测到针对那他珠单抗的抗体。如果抗体持续存在，它们与治疗反应的不良反应相关。然而，事实证明，标准化抗药物抗体的测量具有一定难度。
本研究旨在评估 MS 患者血清那他珠单抗浓度及其与抗那他珠单抗抗体的关系对临床和影像学的影响。
在这项针对 73 例连续接受那他珠单抗治疗的患者的前瞻性观察队列研究中，我们在开始那他珠单抗治疗前、治疗后第 12 周和第 24 周以及开始那他珠单抗治疗后每年测量血清那他珠单抗水平和抗体滴度。采用放射免疫分析和新开发的酶联免疫吸附试验（ELISA）测量抗那他珠单抗抗体，在开始那他珠单抗治疗前和随后每年进行磁共振成像（MRI）扫描和临床评估。
在接受那他珠单抗治疗的患者中，有 58%检测到抗体。所有患者在第 24 周前均产生抗体。这些患者中的绝大多数在随访期间恢复为中和抗体（NAb）阴性状态。抗体的存在与血清那他珠单抗浓度呈负相关（p<0.001）。只有高抗体滴度与非常低或无法检测到的血清那他珠单抗浓度相关。高抗体滴度和低血清那他珠单抗浓度均与 MRI 上的复发和钆增强病变相关。
我们的数据表明，低血清那他珠单抗浓度和高抗体滴度均与那他珠单抗疗效丧失相关。使用高度特异性的检测方法测量血清那他珠单抗可能会提高个体患者使用那他珠单抗的精准度。
