National Centre for Pharmacoeconomics, Dublin, Ireland.
Health Economics and Evidence Synthesis Research Unit, Department of Population Health, Luxembourg Institute of Health, Luxembourg.
Mult Scler Relat Disord. 2016 Sep;9:23-30. doi: 10.1016/j.msard.2016.06.001. Epub 2016 Jun 8.
Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of treatment efficacy varies across all currently available therapies.
To perform a systematic review and network meta-analysis to evaluate the comparative efficacy of available therapies in reducing relapses and disability progression in RRMS.
A systematic review identified 28 randomised, placebo-controlled and direct comparative trials. A network meta-analysis was conducted within a Bayesian framework to estimate comparative annualised relapse rates (ARR) and risks of disability progression (defined by both a 3-month, and 6-month confirmation interval). Potential sources of treatment-effect modification from study-level covariates and baseline risk were evaluated through meta-regression methods. The Surface Under the Cumulative RAnking curve (SUCRA) method was used to provide a ranking of treatments for each outcome.
The magnitude of ARR reduction varied between 15-36% for all interferon-beta products, glatiramer acetate and teriflunomide, and from 50 to 69% for alemtuzumab, dimethyl fumarate, fingolimod and natalizumab. The risk of disability progression (3-month) was reduced by 19-28% with interferon-beta products, glatiramer acetate, fingolimod and teriflunomide, by 38-45% for pegylated interferon-beta, dimethyl fumarate and natalizumab and by 68% with alemtuzumab. Broadly similar estimates for the risk of disability progression (6-month), with the exception of interferon-beta-1b 250mcg which was much more efficacious based on this definition. Alemtuzumab and natalizumab had the highest SUCRA scores (97% and 95% respectively) for ARR, while ranking for disability progression varied depending on the definition of the outcome. Interferon-beta-1b 250mcg ranked among the most efficacious treatments for disability progression confirmed after six months (92%) and among the least efficacious when the outcome was confirmed after three months (30%). No significant modification of relative treatment effects was identified from study-level covariates or baseline risk.
Compared with placebo, clear reductions in ARR with disease-modifying therapies were accompanied by more uncertain changes in disability progression. The magnitude of the reduction and the uncertainty associated with treatment effects varied between DMTs. While natalizumab and alemtuzumab demonstrated consistently high ranking across outcomes, with older interferon-beta and glatiramer acetate products ranking lowest, variation in disability progression definitions lead to variation in the relative ranking of treatments. Rigorously conducted comparative studies are required to fully evaluate the comparative treatment effects of disease modifying therapies for RRMS.
随机研究已经证明了疾病修正疗法在复发缓解型多发性硬化症（RRMS）中的疗效。然而，目前尚不清楚所有可用疗法的治疗效果在多大程度上有所不同。
进行系统评价和网络荟萃分析，以评估 RRMS 中现有疗法在减少复发和残疾进展方面的相对疗效。
系统评价确定了 28 项随机、安慰剂对照和直接比较试验。在贝叶斯框架内进行网络荟萃分析，以估计可用疗法的相对年化复发率（ARR）和残疾进展风险（由 3 个月和 6 个月的确认间隔定义）。通过荟萃回归方法评估了来自研究水平协变量和基线风险的潜在治疗效果修饰来源。使用累积排名曲线下面积（SUCRA）方法对每种结局的治疗方法进行排名。
所有干扰素-β产品、聚乙二醇干扰素-β、那他珠单抗、二甲法尼酯和芬戈莫德的 ARR 降低幅度在 15-36%之间，而阿仑单抗、特立氟胺、醋酸格拉替雷和干扰素-β的 ARR 降低幅度在 50-69%之间。干扰素-β产品、醋酸格拉替雷、芬戈莫德和特立氟胺使残疾进展（3 个月）的风险降低了 19-28%，聚乙二醇干扰素-β、二甲法尼酯和那他珠单抗降低了 38-45%，阿仑单抗降低了 68%。基于此定义，干扰素-β-1b 250mcg 对残疾进展（6 个月）的风险估计大致相似，但疗效更高。阿仑单抗和那他珠单抗的 ARR 排名最高（分别为 97%和 95%），而残疾进展的排名则取决于结局的定义。干扰素-β-1b 250mcg 在经过六个月确认后被列为最有效的残疾进展治疗方法之一（92%），而在经过三个月确认后则被列为最无效的治疗方法之一（30%）。从研究水平协变量或基线风险来看，没有发现相对治疗效果的显著修饰。
与安慰剂相比，疾病修正疗法明显降低了 ARR，同时残疾进展的变化也不确定。不同 DMT 之间的减少幅度和与治疗效果相关的不确定性有所不同。虽然阿仑单抗和那他珠单抗在所有结局中表现出一致的高排名，而较老的干扰素-β和醋酸格拉替雷产品排名最低，但残疾进展定义的变化导致了治疗方法相对排名的变化。需要进行严格的对照研究，以充分评估 RRMS 中疾病修正疗法的比较治疗效果。
