Brown M G, Kirby S, Skedgel C, Fisk J D, Murray T J, Bhan V, Sketris I S
Health Outcomes Research Unit, Capital Health District, Nova Scotia, Canada.
Neurology. 2007 Oct 9;69(15):1498-507. doi: 10.1212/01.wnl.0000271884.11129.f3. Epub 2007 Aug 15.
Our objective was to estimate the effectiveness of disease-modifying drugs (DMDs) in delaying multiple sclerosis (MS) disability progression in relapsing-onset (R-onset) definite MS patients under "real-world" conditions.
Treatment effect size, for DMDs as a class, was estimated in absolute terms and relative to MS natural history. A basic model estimated annual Expanded Disability Status Scale (EDSS) change before and after treatment. An expanded model estimated annual EDSS change in pretreatment years, treatment years on first drug, treatment years after drugs were switched, and in years after treatment stopped. Models were populated with 1980 through 2004 clinical data, including 1988 through 2004 data for all Nova Scotians treated with DMDs. Estimates were made for relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and R-onset groups.
Estimated pretreatment annual EDSS increases were approximately 0.10 of one EDSS point for the RRMS group, 0.31 for the SPMS group, and 0.16 for the R-onset group. Estimates of EDSS increase avoided per treatment year on the first drug were significant for the RRMS group (-0.103, 0.000), the SPMS group (-0.065, 0.011), and the R-onset group (-0.162, 0.000); relative effect size estimates were 112%, 21%, and 105%. Estimated EDSS progression was faster in years after drug switches and treatment stops.
Our estimates of disease-modifying drug (DMD) relative treatment effect size, in the context of "real-world" clinical practice, are similar to DMD treatment efficacy estimates in pivotal trials, though our findings attained statistical significance. DMDs, as a class, are effective in delaying Expanded Disability Status Scale progression in patients with relapsing-onset definite multiple sclerosis (MS) (90%), although effectiveness is much better for relapsing-remitting MS than for secondary progressive MS groups.
我们的目的是评估疾病修正药物（DMDs）在“现实世界”条件下延缓复发型（R-onset）确诊多发性硬化症（MS）患者残疾进展的有效性。
以绝对数值并相对于MS自然史来估计DMDs作为一类药物的治疗效应大小。一个基本模型估计治疗前后每年的扩展残疾状态量表（EDSS）变化。一个扩展模型估计治疗前年份、首次用药的治疗年份、换药后的治疗年份以及停药后的年份里每年的EDSS变化。模型采用了1980年至2004年的临床数据，包括1988年至2004年所有接受DMDs治疗的新斯科舍人的数据。对复发缓解型MS（RRMS）、继发进展型MS（SPMS）和R-onset组进行了估计。
RRMS组治疗前每年EDSS增加估计约为0.10个EDSS点，SPMS组为0.31，R-onset组为0.16。首次用药时，每组每年避免的EDSS增加估计值对RRMS组（-0.103，0.000）、SPMS组（-0.065，0.011）和R-onset组（-0.162，0.000）均有显著意义；相对效应大小估计值分别为112%、21%和105%。在换药和停药后的年份里，估计的EDSS进展更快。
在“现实世界”临床实践背景下，我们对疾病修正药物（DMD）相对治疗效应大小的估计与关键试验中的DMD治疗疗效估计相似，尽管我们的研究结果具有统计学意义。DMDs作为一类药物，在延缓复发型确诊多发性硬化症（MS）患者的扩展残疾状态量表进展方面是有效的（90%），尽管复发缓解型MS的有效性比继发进展型MS组要好得多。
