Koch Marcus W, Cutter Gary R, Giovannoni Gavin, Uitdehaag Bernard M J, Wolinsky Jerry S, Davis Mat D, Steinerman Joshua R, Knappertz Volker
Departments of Clinical Neurosciences and Community Health Sciences (M.W.K.), University of Calgary, Alberta, Canada; University of Alabama at Birmingham (G.R.C.); Barts and The London School of Medicine and Dentistry (G.G.), London, UK; Vrije Universiteit University Medical Center (B.M.J.U.), Amsterdam, The Netherlands; McGovern Medical School (J.S.W.), Department of Neurology, University of Texas Health Science Center at Houston; Teva Pharmaceutical Industries (M.D.D., J.R.S., V.K.), Frazer, PA; and Heinrich-Heine Universität Düsseldorf (V.K.), Germany.
Neurol Neuroimmunol Neuroinflamm. 2017 May 10;4(4):e358. doi: 10.1212/NXI.0000000000000358. eCollection 2017 Jul.
To assess the comparative utility of disability progression measures in primary progressive MS (PPMS) using the PROMiSe trial data set.
Data for patients randomized to placebo (n = 316) in the PROMiSe trial were included in this analysis. Disability was assessed using change in single (Expanded Disability Status Scale [EDSS], timed 25-foot walk [T25FW], and 9-hole peg test [9HPT]) and composite disability measures (EDSS/T25FW, EDSS/9HPT, and EDSS/T25FW/9HPT). Cumulative and cross-sectional unconfirmed disability progression (UDP) and confirmed disability progression (CDP; sustained for 3 months) rates were assessed at 12 and 24 months.
CDP rates defined by a ≥20% increase in T25FW were higher than those defined by EDSS score at 12 and 24 months. CDP rates defined by T25FW or EDSS score were higher than those defined by 9HPT score. The 3-part composite measure was associated with more CDP events (41.4% and 63.9% of patients at 12 and 24 months, respectively) than the 2-part measure (EDSS/T25FW [38.5% and 59.5%, respectively]) and any single measure. Cumulative UDP and CDP rates were higher than cross-sectional rates.
The T25FW or composite measures of disability may be more sensitive to disability progression in patients with PPMS and should be considered as the primary endpoint for future studies of new therapies. CDP may be the preferred measure in classic randomized controlled trials in which cumulative disability progression rates are evaluated; UDP may be feasible for cross-sectional studies.
利用PROMiSe试验数据集评估残疾进展指标在原发性进展型多发性硬化症（PPMS）中的相对效用。
本分析纳入了PROMiSe试验中随机分配至安慰剂组（n = 316）的患者数据。使用单一指标变化（扩展残疾状态量表[EDSS]、25英尺步行时间[T25FW]和9孔插钉试验[9HPT]）以及综合残疾指标（EDSS/T25FW、EDSS/9HPT和EDSS/T25FW/9HPT）评估残疾情况。在12个月和24个月时评估累积和横断面未确认残疾进展（UDP）以及确认残疾进展（CDP；持续3个月）率。
在12个月和24个月时，由T25FW增加≥20%定义的CDP率高于由EDSS评分定义的CDP率。由T25FW或EDSS评分定义的CDP率高于由9HPT评分定义的CDP率。与两部分指标（EDSS/T25FW[分别为38.5%和59.5%]）和任何单一指标相比，三部分综合指标在12个月和24个月时分别与更多的CDP事件相关（分别为41.4%和63.9%的患者）。累积UDP和CDP率高于横断面率。
T25FW或残疾综合指标可能对PPMS患者的残疾进展更敏感，应被视为未来新疗法研究的主要终点。在评估累积残疾进展率的经典随机对照试验中，CDP可能是首选指标；UDP可能适用于横断面研究。
