The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis
The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis
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DOI：
10.1177/1352458516638941
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发表时间：
2017-01-01
影响因子：
5.8
通讯作者：
Mikol, Daniel
中科院分区：
文献类型：
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作者：
Cadavid, Diego;Cohen, Jeffrey A.;Mikol, Daniel
背景：扩展残疾状态量表（EDSS）具有广泛的科学和监管先例，但在继发性进行性多发性硬化症（SPMS）患者中检测临床相关残疾进展的能力有限，部分原因是缺乏对短距离活动和上肢功能的有意义的测量。目的：提出将定时25英尺步行（T25FW）和9孔Peg测试（9HPT）添加到EDSS中用于SPMS残疾进展评估的复合终点的基本原理。方法：使用国际多发性硬化症继发性进行性Avonex临床试验（IMPACT）安慰剂组（n = 215）数据，我们使用新的进展终点“EDSS- plus”分析残疾进展，定义为>= 3个成分（EDSS， T25FW和/或9HPT）中的>= 1的进展，确认>= 24周间隔，>= 20%的最低阈值变化T25FW和9HPT。结果：2年内，T25FW、9HPT（优势手）、9HPT（非优势手）进展者的病情加重率平均分别为103.4%、69.0%和59.2%，而非进展者的病程基本保持不变。使用EDSS- plus， 59.5%的患者24周确认残疾进展，而单独使用每种成分的患者为24.7% (EDSS), 41.9% （T25FW）和34.4% （9HPT（双手））。结论：T25FW和9HPT患者24周确认>= 20%的最小恶化明显区分了SPMS进展者和非进展者。我们认为EDSS-Plus可能是识别SPMS残疾进展的一个改进的终点。
Background: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function.Objective: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment.Methods: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm (n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on >= 1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed >= 24 weeks apart and with a >= 20% minimum threshold change for T25FW and 9HPT.Results: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone.Conclusion: The 24-week confirmed minimum worsening of >= 20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.