背景:在许多多发性硬化(MS)患者中,由于进行性多灶性白质脑病(PML)的风险,无法使用那他珠单抗(NTZ)。无论如何,尽管血清反应呈阳性,但一些患者可能会开始使用那他珠单抗进行短期疾病控制,和其他人可能在治疗时血清转化。在这种情况下,在制定明确的退出策略以防止NTZ后疾病重新激活之前,不应停止NTZ,通常超过NTZ治疗前疾病活动的严重程度。本系统综述的目的是总结CD20单克隆抗体(CD20mAb)作为合适的NTZ退出策略的现有证据。并确定是否可以建立高级交换协议。
方法:根据PRISMA指南,从三个在线数据库(PubMed,Scopus,MEDLINE)。在应用纳入/排除标准后,共纳入5项研究,共331例患者.
结果:在4.4-10.7周范围内的临床复发总发生率为0%。在两年的随访期间,对于转换为所有类型的CD20单克隆抗体,临床复发的发生率为1.8%至10%。12个月时临床复发的加权平均值为8.8%。三项研究报告年复发率(ARR)为0.02-0.12,加权平均ARR为0.07。冲洗期间PML的总发生率为0%,随访6个月内PML的总发生率为0.6%。
结论:本系统综述首次尝试在有从NTZ转变为CD20mAb的PML风险的患者中确定优越的转换方案。我们的结果表明,CD20mAb是一个合适的过渡选择谁停止NTZ,我们的队列显示,PML的残留率非常低,临床复发率低。由于混杂因素,最合适的清除期尚不清楚,但可能在4至12周之间。
BACKGROUND: Use of natalizumab (NTZ) is precluded in many Multiple Sclerosis (MS) patients by the risk of progressive multifocal leukoencephalopathy (
PML). Regardless, some patients may commence natalizumab for short term disease control in spite of being seropositive, and others may seroconvert whilst on treatment. In these circumstances, discontinuation of NTZ should not occur until a clear exit strategy is established to prevent post-NTZ disease reactivation, which often exceeds the severity of disease activity prior to NTZ treatment. The objective of this systematic
review was to summarise the available evidence for CD20-monoclonal antibodies (CD20mAb) as a suitable NTZ exit strategy, and to identify whether a superior switch protocol can be established.
METHODS: In accordance with PRISMA guidelines, a total of 2393 references were extracted from a search of three online databases (PubMed, Scopus, MEDLINE). Following the application of inclusion/exclusion criteria, a total of 5 studies representing 331 patients were included.
RESULTS: The overall incidence of clinical relapse during washout periods ranging from 4.4-10.7 weeks was 0 %. The incidence of clinical relapse during two-year follow-up ranged from 1.8 % to 10 % for switches to all types of CD20 monoclonal antibody. The weighted mean for clinical relapse at 12 months was 8.8 %. Three studies reported an annualised relapse rate (ARR) ranging from 0.02-0.12 with a weighted mean ARR of 0.07. The overall incidence of
PML during washout was 0 % and the overall incidence of
PML within 6 months follow-up was 0.6 %.
CONCLUSIONS: This systematic
review provides the first attempt at identifying a superior switch protocol in patients at risk of
PML transitioning from NTZ to a CD20mAb. Our results indicate that CD20mAb\'s are a suitable transitional option for patients who discontinue NTZ, with our cohort demonstrating very low rates of carryover PML and low rates of clinical relapse. The most appropriate washout period is unclear due to confounding factors but is likely between 4 and 12 weeks.