Université de Lyon, Université Claude Bernard, Lyon 1, Lyon, France.
Service de Neurologie, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Bron, France.
Neurotherapeutics. 2022 Mar;19(2):476-490. doi: 10.1007/s13311-022-01202-1. Epub 2022 Feb 25.
In France, two therapeutic strategies can be offered after fingolimod (FNG) withdrawal to highly active relapsing-remitting multiple sclerosis (RRMS) patients: natalizumab (NTZ) or anti-CD20. We compared the effectiveness of these two strategies as a switch for FNG within the OFSEP database. The primary endpoint was the time to first relapse. Other outcomes were the relapse rates over 3-month periods, time to worsening the EDSS score, proportion of patients with worsened 24-month MRI, time to treatment discontinuation, and incidence rates of serious adverse events. The dynamics of event rates over time were modeled using multidimensional penalized splines, allowing the possibility to model the effects of covariates in a flexible way, considering non-linearity and interactions. A total of 740 patients were included (337 under anti-CD20 and 403 under NTZ). There was no difference between the two treatments regarding the dynamic of the first occurrence of relapse, with a monthly probability of 5.0% at initiation and 1.0% after 6 months. The rate of EDSS worsening increased in both groups until 6 months and then decreased. No difference in the proportion of patients with new T2 lesions at 24 months was observed. After 18 months of follow-up, a greater risk of NTZ discontinuation was found compared to anti-CD20. This study showed no difference between NTZ and anti-CD20 after the FNG switch regarding the clinical and radiological activity. The effect of these treatments was optimal after 6 months and there was more frequent discontinuation of NTZ after 18 months, probably mainly related to JC virus seroconversions.
在法国，对于 fingolimod（FNG）停药后的高度活跃复发缓解型多发性硬化症（RRMS）患者，可以提供两种治疗策略：那他珠单抗（NTZ）或抗 CD20。我们在 OFSEP 数据库中比较了这两种策略作为 FNG 转换的效果。主要终点是首次复发的时间。其他结局包括 3 个月期间的复发率、EDSS 评分恶化的时间、24 个月 MRI 恶化的患者比例、治疗停止的时间以及严重不良事件的发生率。使用多维惩罚样条来模拟事件率随时间的动态，允许以灵活的方式考虑协变量的影响，考虑非线性和相互作用。共纳入 740 例患者（抗 CD20 组 337 例，NTZ 组 403 例）。两种治疗方法在首次复发的动态方面没有差异，起始时每月的复发概率为 5.0%，6 个月后为 1.0%。两组 EDSS 恶化率均增加，直至 6 个月，然后下降。在 24 个月时，新 T2 病变的患者比例没有差异。在 18 个月的随访后，与抗 CD20 相比，NTZ 停药的风险更高。这项研究表明，在 FNG 转换后，NTZ 和抗 CD20 之间在临床和放射学活动方面没有差异。这些治疗的效果在 6 个月后最佳，18 个月后 NTZ 更频繁地停药，可能主要与 JC 病毒血清转化有关。
