Huisman Eline, Papadimitropoulou Katerina, Jarrett James, Bending Matthew, Firth Zoe, Allen Felicity, Adlard Nick
Mapi Group, Houten, The Netherlands.
Mapi Group, London, UK.
BMJ Open. 2017 Mar 10;7(3):e013430. doi: 10.1136/bmjopen-2016-013430.
Multiple sclerosis (MS) is a chronic, neurodegenerative autoimmune disorder affecting the central nervous system. Relapsing-remitting MS (RRMS) is the most common clinical form of MS and affects ∼85% of cases at onset. Highly active (HA) and rapidly evolving severe (RES) RRMS are 2 forms of RRMS amenable to disease-modifying therapies (DMT). This study explored the efficacy of fingolimod relative to other DMTs for the treatment of HA and RES RRMS.
A systematic literature review (SLR) was conducted to identify published randomised controlled trials in HA and RES RRMS. Identified evidence was vetted, and a Bayesian network meta-analysis (NMA) was performed to evaluate the relative efficacy of fingolimod versus dimethyl fumarate (DMF) in HA RRMS and versus natalizumab in RES RRMS.
For HA RRMS, the SLR identified 2 studies with relevant patient subgroup data: 1 comparing fingolimod with placebo and the other comparing DMF with placebo. 3 studies were found for RES RRMS: 1 comparing fingolimod with placebo and 2 studies comparing natalizumab with placebo. NMA results in the HA population showed a favourable numerical trend of fingolimod versus DMF assessed for annualised relapse rate (ARR) and 3-month confirmed disability progression. For the RES population, the results identified an increase of ARR and 3-month confirmed disability progression for fingolimod versus natalizumab (not statistically significant). Sparse study data and the consequently high uncertainty around the estimates restricted our ability to demonstrate statistical significance in the studied subgroups.
Data limitations are apparent when conducting an informative indirect comparison for the HA and RES RRMS subgroups as the subgroups analyses were retrospective analyses of studies powered to indicate differences across entire study populations. Comparisons across treatments in HA or RES RRMS will be associated with high levels of uncertainty until new data are collected for these subgroups.
多发性硬化症（MS）是一种影响中枢神经系统的慢性神经退行性自身免疫性疾病。复发缓解型多发性硬化症（RRMS）是MS最常见的临床形式，约85%的病例起病时为此类型。高度活动型（HA）和快速进展型严重（RES）RRMS是RRMS的两种类型，适合采用疾病修正疗法（DMT）。本研究探讨了芬戈莫德相对于其他DMT治疗HA和RES RRMS的疗效。
进行了一项系统文献综述（SLR），以确定已发表的关于HA和RES RRMS的随机对照试验。对识别出的证据进行审查，并进行贝叶斯网络荟萃分析（NMA），以评估芬戈莫德与富马酸二甲酯（DMF）在HA RRMS中的相对疗效，以及与那他珠单抗在RES RRMS中的相对疗效。
对于HA RRMS，SLR识别出2项具有相关患者亚组数据的研究：1项比较芬戈莫德与安慰剂，另一项比较DMF与安慰剂。RES RRMS方面发现了3项研究：1项比较芬戈莫德与安慰剂，2项研究比较那他珠单抗与安慰剂。NMA在HA人群中的结果显示，在年化复发率（ARR）和3个月确诊的残疾进展方面，芬戈莫德相对于DMF有有利的数值趋势。对于RES人群，结果显示芬戈莫德相对于那他珠单抗的ARR和3个月确诊的残疾进展有所增加（无统计学意义）。研究数据稀少，因此估计值周围的不确定性很高，限制了我们在研究亚组中证明统计学意义的能力。
在对HA和RES RRMS亚组进行信息丰富的间接比较时，数据局限性很明显，因为亚组分析是对旨在表明整个研究人群差异的研究进行的回顾性分析。在收集到这些亚组的新数据之前，HA或RES RRMS中不同治疗方法之间的比较将伴随着高度的不确定性。
