“When you have MS and you lose the function of your legs, your arms and hands become your legs. When you lose the function of your arms your lips, tongue and throat muscles become your arms, hands and legs. At the moment we seem to focus too much attention on leg function and forget the upper body. In the NHS we are meant to stop DMTs when a person becomes wheelchair bound; what we actually saying to them is we don’t really care about your upper limb or bulbar function. Clearly this position is wrong and we need to do something about it. Data will emerge later this year that DMTs continue to work on the upper limbs despite lower limb function working. What this observation is telling is that MS is that the pathogenesis of MS may be modifiable regardless of how disabled you are.”
Cadavid et al. The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis. Mult Scler. 2016 Mar 22. pii: 1352458516638941.
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.