Department "GF. Ingrassia", Section of Neurosciences, University of Catania, via S. Sofia 78, 95129, Catania, Italy.
Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Neurol. 2022 Feb;269(2):933-944. doi: 10.1007/s00415-021-10676-6. Epub 2021 Jun 28.
Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients.
The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as "lack of efficacy", "progressive multifocal leukoencephalopathy (PML) risk" or "other".
Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1 years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy [1682 (32.7% of 5151) vs 221 (4.3%), p < 0.001]; other reasons were identified for 99 (1.9%) patients. Patients discontinuing treatment were older, had longer disease duration and worse EDSS at the time of NTZ initiation and at last follow-up on NTZ treatment. The JCV index and EDSS at baseline were predictors for stopping therapy (HR 2.94, 95% CI 1.22-4.75; p = 0.02; HR 1.36, 95% CI 1.18-5.41; p = 0.04).
Roughly 60% of MS patients stayed on NTZ treatment during the observation period. For those patients in whom NTZ discontinuation was required, it was mainly due to PML concerns.
那他珠单抗（NTZ）是治疗复发缓解型多发性硬化症（RRMS）的有效药物。然而，由于安全性或疗效问题，患者和医生可能会考虑停止 NTZ 治疗。本研究的目的是评估意大利大型 RRMS 患者人群中 NTZ 的停药率和停药原因。
数据于 2018 年 5 月从意大利多发性硬化症登记处提取，收集了来自意大利 69 个多发性硬化症中心的 51845 名患者的数据。纳入了在 2012 年 6 月 1 日至 2018 年 5 月 15 日期间至少接受过一次 NTZ 输注的 MS 患者。计算了每个时间点的停药率。将 NTZ 停药的原因分为“无疗效”、“进行性多灶性白质脑病（PML）风险”或“其他”。
在 51845 名患者中，有 5151 名（3019 名女性，平均年龄 43.6±10.1 岁[中位数 40]）进行了分析。在 2037 名（39.5%）停止使用 NTZ 的患者中，由于 PML 风险而停止使用 NTZ 的比例明显高于无疗效的患者[1682 名（5151 名的 32.7%）比 221 名（4.3%），p<0.001]；其他原因导致 99 名（1.9%）患者停药。停止治疗的患者年龄较大，在开始使用 NTZ 时和最后一次 NTZ 治疗时疾病持续时间更长，EDSS 评分更高。JC 病毒指数和基线时的 EDSS 是停止治疗的预测因素（HR 2.94，95%CI 1.22-4.75；p=0.02；HR 1.36，95%CI 1.18-5.41；p=0.04）。
在观察期间，大约 60%的 MS 患者继续接受 NTZ 治疗。对于那些需要停止 NTZ 治疗的患者，主要原因是 PML 风险。
