The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis

Abstract

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.

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

“…The primary outcome in part 1 was based on a multicomponent measure of sustained disability progression comprising the EDSS, T25FW, and 9HPT, and was designed to provide a more sensitive and specific measure of disease worsening in secondary progressive multiple sclerosis than EDSS alone. 22 The primary endpoint was the proportion of patients with confirmed disability progression over the 96 week treatment period, with progression defined as meeting one or more of the following three criteria: an increase of 1·0 points or more from a baseline score of 5·5 or lower or an increase of 0·5 points or more from a baseline score of 6·0 or higher on the EDSS; an increase of 20% or more from baseline on the T25FW; or an increase of 20% or more from baseline (on either hand) on the 9HPT. Progression was confirmed at a subsequent visit 6 or more months after the start of a possible progression and at the end of the trial.…”

“…Detecting change with available validated outcome measures in a slowly progressing multiple sclerosis population over a short period of observation is difficult. The multicomponent endpoint used in this study might be more sensitive to changes in disability than the EDSS alone, 22 but two of its three components focus on lower limb function and were not affected by treatment. The EDSS, in particular, has been shown to have poor responsiveness to disease progression and treatment effects in patients with high baseline scores.…”

Comparative utility of disability progression measures in PPMS

“…18,19 In one of these studies, however, the patient population consisted entirely of those with secondary progressive MS, 18 whereas the other had a lower EDSS inclusion threshold (1–7), allowed inclusion of patients who had been treated with DMTs as recently as 3 months prior to study entry, and was intended as a validation study of a novel disability score (CombiWISE); that scoring measure, in addition to EDSS, T25FW, and 9HPT, also includes the Scripps Neurological Rating Scale. 19 And, as with the previously noted studies, neither unconfirmed disease nor a cross-sectional analysis was included in the design of these studies.…”

“…19 And, as with the previously noted studies, neither unconfirmed disease nor a cross-sectional analysis was included in the design of these studies. 18,19 Thus, this study offers several unique features that make it a potentially valuable contribution to the literature, such as reflecting the untreated natural history of PPMS by including only patients receiving placebo, including patients with more severe disability, comparing confirmed and unconfirmed disease progression, and including a cross-sectional analysis.…”

Infratentorial and spinal cord lesions: Cumulative predictors of long-term disability?

“…25 The EDSS-plus is a more extensive assessment for disability progression, defined as progression on EDSS as described above or a 20% increase at FU on the 25-FWT or 9-HPT. 24…”