Department of Neurology, Nitobe Memorial Nakano General Hospital, 4-59-16, Chuo, Nakano-ku, Tokyo, Japan.
Department of Neurology and Neurological Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan.
Neurol Sci. 2018 Oct;39(10):1713-1716. doi: 10.1007/s10072-018-3487-y. Epub 2018 Jul 4.
No evidence of disease activity-3 (NEDA-3), defined as absence of clinical relapse, disability progression, and brain magnetic resonance imaging (MRI) activity, has emerged as the therapeutic target of disease-modifying therapy for multiple sclerosis (MS). However, recent studies have revealed that NEDA-3 might not be sufficient to prevent cognitive deterioration and predict long-term disability. In addition to NEDA-3, brain atrophy has recently been recognized as a pivotal biomarker that is closely associated to disability in patients with MS. This retrospective observational study included 22 Japanese MS patients with relatively mild disease (median expanded disability status scale = 1.75). Fifteen patients (68%) received disease-modifying therapy (DMT), including interferon (IFN)-β (n = 6), IFN-β, or azathioprine followed by fingolimod (n = 4), fingolimod (n = 4), and IFN-β followed by natalizumab (n = 1). It revealed that 14 (64.6%) patients achieved NEDA-3 in the 2-year observational period. However, nine (64.3%) of the patients with NEDA-3 were revealed to have a significant BVL, defined as ≥ 0.4% per year. Importantly, these nine patients included all patients receiving IFN-β therapy (n = 6), whereas patients without BVL included none of these patients. Conversely, patients treated with fingolimod following IFN-β did not have significant BVL. These results indicate that evaluation of NEDA-4 is encouraged especially in patients with IFN-β therapy in MS clinical practice in Japan although Japanese MS patients have generally been thought to possess a milder disease including brain atrophy compared to their Western counterparts.
无疾病活动-3（NEDA-3）作为多发性硬化症（MS）疾病修饰疗法的治疗靶点已经出现，其定义为无临床复发、残疾进展和脑磁共振成像（MRI）活动。然而，最近的研究表明，NEDA-3 可能不足以预防认知恶化和预测长期残疾。除了 NEDA-3，脑萎缩最近被认为是与 MS 患者残疾密切相关的关键生物标志物。这项回顾性观察性研究纳入了 22 名疾病相对较轻的日本 MS 患者（中位数扩展残疾状况量表为 1.75）。15 名患者（68%）接受了疾病修饰疗法（DMT），包括干扰素（IFN）-β（n=6）、IFN-β或硫唑嘌呤，随后使用芬戈莫德（n=4）、芬戈莫德（n=4）和 IFN-β，随后使用那他珠单抗（n=1）。结果显示，在 2 年观察期内，14 名（64.6%）患者达到了 NEDA-3。然而，9 名（64.3%）达到 NEDA-3 的患者出现了显著的脑体积损失（BVL），定义为每年≥0.4%。重要的是，这 9 名患者均接受了 IFN-β治疗（n=6），而无 BVL 的患者中没有接受 IFN-β治疗的患者。相反，接受 IFN-β 治疗后使用芬戈莫德的患者未出现显著的 BVL。这些结果表明，尽管与西方患者相比，日本 MS 患者的疾病包括脑萎缩在内一般较轻，但在日本的 MS 临床实践中，鼓励对接受 IFN-β治疗的患者评估 NEDA-4。
