Journal
MULTIPLE SCLEROSIS JOURNAL
Volume 23, Issue 1, Pages 94-105Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458516638941
Keywords
Disability evaluation; disease progression; endpoint determination; secondary progressive multiple sclerosis
Categories
Funding
- Biogen (Cambridge, MA, USA)
- Czech Ministry of Education [PRVOUK-P26/LF1/4]
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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.
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